Practical Issues in Geriatrics

Series Editor: Stefania Maggi

Giuseppe Guglielmi
Mario Maas Editors

Imaging in
Geriatrics
Practical Issues in Geriatrics
Series Editor
Stefania Maggi, Aging Branch
CNR-Neuroscience Institute, Padua, Italy

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This practically oriented series presents state of the art knowledge on the principal
diseases encountered in older persons and addresses all aspects of management,
including current multidisciplinary diagnostic and therapeutic approaches. It is
intended as an educational tool that will enhance the everyday clinical practice of
both young geriatricians and residents and also assist other specialists who deal
with aged patients. Each volume is designed to provide comprehensive information
on the topic that it covers, and whenever appropriate the text is complemented by
additional material of high educational and practical value, including informative
video-clips, standardized diagnostic flow charts and descriptive clinical cases.
Practical Issues in Geriatrics will be of value to the scientific and professional
community worldwide, improving understanding of the many clinical and social
issues in Geriatrics and assisting in the delivery of optimal clinical care.
Giuseppe Guglielmi • Mario Maas
Editors

Imaging in Geriatrics

AL GRAWANY
Editors
Giuseppe Guglielmi Mario Maas
Clinical and Experimental Medicine Department of Radiology and Nuclear
University of Foggia Medicine
Foggia, Italy University of Amsterdam
Amsterdam, Noord-Holland
The Netherlands

ISSN 2509-6060     ISSN 2509-6079 (electronic)

Practical Issues in Geriatrics
ISBN 978-3-031-14876-7    ISBN 978-3-031-14877-4 (eBook)
https://doi.org/10.1007/978-3-031-14877-4

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Preface

Demographic changes, due to the longer lifespan and the improvement of the qual-
ity of life, led to an aging society, where developing high-quality healthcare for
older people becomes increasingly important.
Nowadays the elderly population is more informed and more demanding of bet-
ter care through cutting-edge technology and treatment. Specifically, radiologists
play an increasingly important role and occupy a frontline position in the evaluation
of this cohort of patients, who necessitate definitive imaging.
In this perspective, the complex relationship between geriatrics and radiology
must be redefined. Imaging in Geriatrics is the result of a teamwork of radiologists,
experts in the field, with the aim to provide guidance for the appropriate use of
imaging in modern geriatric care, describing how to recognize pathology from para-
physiological findings in the elderly population.
The study of diagnostic imaging in geriatrics, enriched by traditional and modern
imaging methods, is primarily oriented to the clinical and radiological analysis most
frequently encountered in these patients and, above all, to the not easy distinction
between “normal” and “pathological,” especially in situations in which para-physi-
ological changes resulting from aging processes are associated with alterations
related to comorbidity and chronicity.
This volume includes a multidisciplinary approach, and it covers all major medi-
cal issues related to aging, divided by apparatus. In particular, it encloses the main
pathologies in the neurological, cardiovascular, pulmonary, gastrointestinal, uro-
genital, hematologic, and musculoskeletal field.
This book considers all imaging techniques that have been the cornerstones of
radiology, but also modern innovations. Conventional radiography is still the first
approach in the diagnosis of a frequent variety of pathological conditions of elderly
patients, such as fractures, often due to osteoporosis, pneumothorax, or heart fail-
ure. On the other hand, Computer Tomography (CT), with its intrinsic resolution
power, allows radiologists to detect a possible ischemic or hemorrhagic cerebral
focus, as well as neoplastic metastases for the staging of the primary pathology.
Spinal cord injuries are best identified with Magnetic Resonance Imaging (MRI).
But nowadays, and therefore modern “tailored” medicine, is changing, going
towards Artificial Intelligence (AI), a technological evolution that brings with it the
limits related to the training and updating of the healthcare personnel involved. For

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vi Preface

this reason, a section about the role of AI in the management of geriatric patients
could not be missed at the end of this volume.
Finally, the aim of this book is to simplify the approach and the diagnostic imag-
ing process of geriatric diseases, bringing out the potential and limitations of each
imaging technique.
We recommend the reading of this book not only to radiologists for their daily
clinical practice but also to all physicians who require a basic knowledge of imaging
concerning the main geriatric pathologies, because of their complex clinical
presentations.

Foggia, Italy Giuseppe Guglielmi

Amsterdam, The Netherlands Mario Maas
Contents

1 
Imaging Techniques in Geriatric Patients ����������������������������������������������   1
Caterina Bernetti, Carlo Augusto Mallio, Rosario Francesco Grasso,
and Bruno Beomonte Zobel
2 
Neurodegenerative Diseases in Geriatric Patients���������������������������������� 11
Camilla Russo, Rossana Senese, and Mario Muto
3 
Neurovascular Emergencies in Geriatric Patients���������������������������������� 37
Giuseppe Maria Di Lella, Luca Ausili Cefaro,
and Cesare Colosimo
4 
Head and Neck in Geriatric Patients ������������������������������������������������������ 73
T. Popolizio, L. Cassano, A. Pennelli, R. Izzo, G. Fascia,
M. Masciavè, and Giuseppe Guglielmi
5 
Heart Diseases in Geriatric Patients�������������������������������������������������������� 109
Anna Palmisano, Raffaele Ascione, Francesco De Cobelli,
and Antonio Esposito
6 
Vascular Diseases in Geriatric Patients��������������������������������������������������� 137
Gloria Caredda, Giuseppe Guglielmi, and Luca Saba
7 
Airway Diseases in Geriatric Patients������������������������������������������������������ 151
Maurizio Balbi, Roberta Eufrasia Ledda, Silvia Pamparino,
Gianluca Milanese, Mario Silva, and Nicola Sverzellati
8 
Neoplastic Diseases of the Respiratory System in Geriatric Patients �� 171
Zeno Falaschi, Francesco Filippone, Sergio Pansini, Stefano Tricca,
Paola Basile, Sara Cesano, and Alessandro Carriero
9 
The Gastrointestinal System in Geriatric Patients �������������������������������� 217
Damiano Caruso, Domenico De Santis, Francesco Pucciarelli,
and Andrea Laghi
10 
The Male Urogenital System in Geriatric Patients �������������������������������� 235
Emilio Quaia and Filippo Crimí

vii

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viii Contents

11 
The Female Urogenital System in Geriatric Patients ���������������������������� 271
Maria Assunta Cova, Lorella Bottaro, Cristina Marrocchio,
and Alessandro Marco Bozzato
12 
Osteoarthritis in Axial Skeleton in Geriatric Patients���������������������������� 319
Francesca Serpi, Salvatore Gitto, and Luca Maria Sconfienza
13 
Osteoarthritis in Appendicular Skeleton in Geriatric Patients ������������ 345
Antonio Barile, Riccardo Monti, Federico Bruno, Julia Daffinà,
Francesco Arrigoni, and Carlo Masciocchi
14 
Metabolic Bone Disease in Geriatric Patients ���������������������������������������� 367
Maria Pilar Aparisi Gómez, Francisco Aparisi, Giuseppe Guglielmi,
and Alberto Bazzocchi
15 
Body Composition in Geriatric Patients�������������������������������������������������� 397
Maria Pilar Aparisi Gómez, Francisco Aparisi, Giuseppe Guglielmi,
and Alberto Bazzocchi
16 
Myeloid and Lymphoid Disorders in Geriatric Patients������������������������ 427
Patrizia Toia, Massimo Galia, Giuseppe Filorizzo,
Ludovico La Grutta, Federico Midiri, Pierpaolo Alongi,
Emanuele Grassedonio, and Massimo Midiri
17 The Role of Artificial Intelligence (AI) in the Management
of Geriatric Patients���������������������������������������������������������������������������������� 445
Salvatore Claudio Fanni, Sherif Mohsen Shalaby,
and Emanuele Neri
Imaging Techniques in Geriatric Patients
1
Caterina Bernetti, Carlo Augusto Mallio,
Rosario Francesco Grasso, and Bruno Beomonte Zobel

1.1 Introduction: The Delicate Balance of Imaging

in the Elderly

In the last decades, there has been a rising trend toward global population aging,
especially in developed nations. This longevity revolution is happening faster than
historical precedents and a further increase of median age is expected in subsequent
years [1].
The improvement of living conditions and the advent of modern medicine carry-
ing innovations in treatment and prevention are some of the main reasons of
increased life expectancy.
This demographic change is determining a profound impact on society, in par-
ticular with regard to the healthcare system, that now has to face more age-related
diseases [2, 3].
In particular, people over 65 years, defined by convention as elderly, are more
prone to develop multiple chronic conditions, such as cardiovascular diseases,
dementia, cancer, and also osteoporosis that could lead to fragility fractures after
minor traumas [4].
In this population, there is an intrinsic difficulty in distinguishing the boundary
between para-physiologic modifications determined by aging and real pathologic
conditions. Furthermore, given the possibility of an incomplete medical history, the
complexity of symptoms and signs determined by the coexistence of multiple
comorbidities, and the reduced sensitivity of laboratory tests, the diagnosis is often
difficult to achieve. In this context, radiological imaging plays an important role in
the diagnostic workup of elderly patients [2, 5].

C. Bernetti · C. A. Mallio · R. F. Grasso · B. B. Zobel (*)

Imaging Center, Diagnostic Imaging and Interventional Radiology Department, University
Hospital “Campus Bio-Medico”, Rome, Italy
e-mail: [email protected]; [email protected];
[email protected]; [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 1

G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_1

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2 C. Bernetti et al.

In the elderly, even more than the rest of the population, the first medical contact
is often represented by the general practitioner, who necessarily needs to be
equipped with adequate knowledge in order to suggest the appropriate specialist
referral or radiological examination [6]. Whereas, in a hospital setting, the two main
figures who will have to interface are the geriatrician and the radiologist, in associa-
tion with all the other specialists who may be involved. In order to provide high-
quality care, they must cooperate in the choice of the appropriate examination and
in the correct management of the patient, with medical and paramedical staff trained
with age-specific skills [7, 8]. Empathy is one of the main features that the health-
care personnel caring for the elderly patient should own [9].
The imaging examination must be chosen wisely, must be of clinical utility, and
must help modify patients management, without exposing them to unnecessary
stress or risks; in fact patients’ safety must be considered as the priority [10].
The goals of the exam are an improvement in the quality of life, the preservation
of functionality of these frail patients, and the prevention of progression from dis-
ease to disability [3].
In the decision process to find the appropriate image technique, the clinicians
must integrate several information, such as functional and mental status, and also
comorbidities, for instance chronic renal impairment, cardiac disfunction, poor
peripheral venous access, and dementia. Immobility and respiratory problems that
impair breath holds must be taken into consideration too, because could alter image
quality [3].
Handling elderly patients in the radiology department is burden by many diffi-
culties; this population need to be treated with caution and special care as their
conditions easily deteriorate. Logistical issues are one of the main challenges that
need to be addressed, in fact these patients often have mobility problems, need
supervision while being transferred to the radiology department and assistance
while waiting to perform the exam [2].
Proper positioning is more time-consuming and the maneuvering of the patient
needs more qualified trained staff [2]. Elders usually have decreased agility and
strength; hence, movements could be impaired, sense of balance could be altered,
and some patient could be unable to maintain required positions. In order to move
them safely and position them adequately, their cooperation and compliance need to
be elicited if possible. Specific movers and support devices are useful to position
and immobilize them. Attention need to be paid while having more independent
patients move or even walk, because they could misjudge distances [3]. The unfa-
miliar and cold environment of radiology rooms and equipment could frighten this
fragile patients; blankets are used to offer adequate warmth, privacy, and dignity.
Healthcare providers must never leave the patient alone; moreover, they need to
be aware of any sign of pain or discomfort, because in the elderly, sensation of pain
could be altered, and the patients could also have trouble expressing themselves [3].
Communication abilities of geriatric patients are often impaired because of many
conditions, such as reduced acuity of vision and hearing, depression, or dementia
[4]. Elders can have difficulties in understanding the procedures and in complying
with instructions to remain still. Speaking clearly, using gestures, beepers, and
1 Imaging Techniques in Geriatric Patients 3

lights could help to transmit information. In particular, for some examinations,

breathing instructions are fundamental and must be carefully communicated and
practiced [7]. Long diagnostic examination, that requires to be in a stationary posi-
tion, is often unsuitable for this population; however, in some particular cases, seda-
tion could be proposed and performed [9].
Sometimes it is difficult, or even impossible, to obtain written consent, because
of the age-related alterations mentioned above; hence, an important point of con-
cern that needs to be addressed and considered in the management of the senile
population is family and social support. Caregivers need to be informed about the
course of the exams and sometimes even involved in the preparation [11].
The purpose of this chapter is to describe the main imaging techniques used in
elderly patients and the peculiar challenges and precautions that must be taken in
specific conditions for the appropriate use of diagnostic and interventional exams in
this complex cohort of patients.

1.2 Imaging Modalities

1.2.1 Plain Radiography in Geriatric Patients

Thanks to its availability and low costs, plain radiography often represents the ini-
tial tool for the diagnosis of many pathologic conditions, including pulmonary, car-
diovascular, and musculoskeletal disorders in older adults. This technique offers as
advantages low costs, celerity in execution, and with modern equipment low radia-
tion exposure.
Correct positioning of the patient is essential to obtain quality images; however,
it could require particular devices, to assure adequate posture and immobilization.
Due to mental impairment or hearing loss, elderly patients often have difficulties
hearing instruction and are not able to collaborate [9]. Short times reduce risk of
involuntary and voluntary motion, more common in the geriatric patients, during
the acquisition [12].
In order to avoid transportation from one department to another, mobile X-ray
equipment with digital panels and radiolucent beds and gurneys can be used in the
hospital setting.
Chest radiography (CXR) is the initial test for the diagnosis of pulmonary, pleu-
ral, and cardiovascular diseases [12]. Radiographs are usually performed in a
posterior-­anterior and a perpendicular lateral projection; however, due to mobility
issues of elderly patients, standard projections often cannot be performed. Hence, a
supine or semi-supine position radiograph has to be taken with some limitations,
such as projective magnification. For lung diseases, such as pneumonia, fibrosis and
lung cancer, sensitivity, and specificity of CXR are quite high. As previously said,
in the elderly, there is a difficulty in recognizing pathologic versus age-related alter-
ations, such as fibrotic changes, emphysema, airways, and rib cage calcification.
Besides this problem, it is also arduous to discern overlapping pathologies in
patients with multiple comorbidities; for example in the case of heart failure versus

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4 C. Bernetti et al.

COPD alterations or pneumonia, which is one of the leading causes of mortality

from infection in older adults, versus other consolidating lung processes [2]. Hence,
it is always fundamental to integrate radiological findings with clinical information
and if further workup is needed, chest computed tomography (CT) should be con-
sidered. Pneumothorax, pleural thickening, and pleural effusions are also evident on
chest radiographs [13].
Cardiovascular diseases are the leading cause of deaths in elderly patients. Even
though chest radiographs is usually the first exam performed, it is often insuffi-
ciently sensitive to rule out pathologic conditions, in fact, often only indirect signs
can be observed [2, 12].
Thoracic aortic dilation, pulmonary edema, pericardial effusion, and cardiomeg-
aly can be evaluated. In case of any abnormality at plain radiographs or persistence
of clinical concern, more sophisticated, time-consuming, and resource-intensive
techniques are needed, such as ultrasound and CT [5].
Elderly population is also burdened by an high prevalence of many musculoskel-
etal disease, such as osteoarthritis, osteoporosis fractures, and degenerative disk
disease.
Osteoarthritis is one of the most common chronic condition afflicting older
adults, causing pain and disability. It can be studied with plain radiographs, usually
performed in two orthogonal projections. Degenerative changes that characterize
this condition are sclerotic changes of the opposing articular surfaces, joint space
narrowing, and osteophyte formation [12].
Plain radiographs also allow postoperative and follow-up of joint replacement
surgery with arthroplasty [14].
Radiographs are relatively insensitive in detecting early osteoporotic alteration,
in fact require an important loss of bone mass to be detected objectively [12].
However, fragility fractures determined by small traumas in a osteoporosis back-
ground are common in the elderly and can be identified with plain radiographs.
Vertebral bodies are the main site for insufficiency fractures in older adults, whereas
femoral fracture often happens after mild traumas or falls and is associated with
high morbidity and mortality [15]. In cases of a suspected fracture, dedicated
oblique views may be helpful and can be added to the standard perpendicular pro-
jections [16]. Traditional radiological diagnosis may be insufficient in the initial
phases in stress fractures [15]. A deepening with CT is necessary in the study of
complex fractures while MRI is the gold standard for occult fractures, post-­traumatic
avascular necrosis, and soft tissue evaluation [5]. Plain radiographs are also used to
evaluate the presence of osteolytic or osteoblastic lesions determined by myeloma,
metastatic lung, breast and prostate cancers, which could also lead to malignant
fractures [5].
Plain radiographs of the abdomen can be considered a valuable resource, in par-
ticular as an initial step in acute settings. Usually a supine and upright views of the
abdomen are performed. If the patient is not able to stand, a left lateral decubitus
view can be obtained as an alternative. This view allows to evaluate the presence of
soft tissue masses, calcifications, bowel gas pattern, air-fluid levels in the intestinal
loops, and free air in the abdomen [17, 18].
1 Imaging Techniques in Geriatric Patients 5

Radiographs are also used in hospitalized patients to verify proper positioning of

medical devices, such as central venous catheter (CVC), feeding tubes, or ure-
teral stents.

1.2.2 Dual-Energy X-Ray Absorptiometry (DXA)

in Geriatric Patients

DXA is the imaging procedure of choice to diagnose osteoporosis, which is one of

the most common pathologic conditions in elders, which can lead to fragility
fractures.
This is a widely accessible, well-standardize technique that quantifies, with pre-
cision, short scan times and low radiation exposure, the areal bone mineral density
(aBMD, g/cm2) using two X-ray beams of different energies (40 keV and
>70 keV) [16].
Usually the regions analyzed are the lumbar spine vertebral bodies and the femo-
ral neck; however, the forearm can be scanned as an alternative if the previous ones
cannot be evaluated [16].
The risk of osteoporotic fractures is increasing in direct proportion to the average
age of the world population, in fact nearly 75% of this fractures occur in geriatric
patients [19].
Correct and early diagnosis of osteoporosis is fundamental, in order to start anti-­
osteoporotic treatment to prevent fragility fractures, which are associated with sig-
nificant morbidity, mortality, and have an important economic impact on the
healthcare system [16].

1.2.3 Ultrasound in Geriatric Patients

In geriatric patients, ultrasound is a useful technique, often underrated, able to pro-

vide prompt diagnosis and treatment to several chronic or acute conditions, related
to splanchnic organs, musculoskeletal system, and arterial or venous vessels [20]. It
is used as a technologic complement to physical examination and laboratory find-
ings because offers numerous advantages. It is patient-friendly, safe, rapid, cost-­
effective, available at short notice and repeatable. Moreover, it does not require
exposure to radiation or magnetic fields, hence, in comparison to CT and MRI has
fewer contraindication [20].
It can also be conveniently used at the bedside at the moment of need, thus allow-
ing a rapid evaluation of the problem, but also avoiding movements of frail
patients [20].
Being a dynamic multiplanar imaging technique, it is possible to perform diag-
nostic and therapeutic interventional radiology procedures under real-time guid-
ance, such as biopsies, thermal ablation, drainage positioning, thus reducing the risk
of complications, such as bleeding.

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6 C. Bernetti et al.

However, there are some issues that need to be underlined. US images are
scarcely reproducible, because it is a patient and operator dependent technique,
which relies on the compliance of the patient and the skills of the radiologist.
Moreover, availability of portable equipment can be limited [21].
Elderly patients are characterized by numerous age-related conditions that could
affect the quality, and hence, the interpretation of the images. For instance, their
tissues and vascular vectors are characterized by fibrosis and calcifications, which
determine an increased sonography echogenicity and compound artifacts [10]. This
cohort of patients is also characterized by reduced bowel movements with a conse-
quent increased amount of gas in the lumen of the intestine, which could lead to
difficulty in the evaluation of abdominal organs, such as the pancreas [10].
Doppler analysis represents a useful feature that allows to evaluate the blood
flow. It can be used in case of suspected deep vein thrombosis (DVP) or to evaluate
atherosclerotic plaques of carotid, iliac, femoral, popliteal, and tibial arteries, often
present in older adults, but also to evaluate blood supply of tumors. However,
motion, in particular respiratory movements, often uncontrollable in the elderly,
could alter the visualization of the color maps.
Contrast ultrasound (CEUS) is performed with an intravenous contrast agent
consisting of gaseous microbubbles that remain in the vascular bed and do not reach
the extravascular spaces. Due to the absence of nephrotoxicity and the possibility of
being repeated, CEUS could be proposed as a valid and safe alternative to CT and
MRI with contrast; however, it must be performed by experienced operators in order
to avoid misinterpretations [22, 23].
In addition to the most common studies (abdomen and thyroid gland), ultrasound
can be used for many conditions, for instance musculoskeletal disorders, which are
considered one of the major chronic conditions affecting the senile population.
Vessel evaluation can be performed with color-Doppler, for instance to predict car-
diovascular and neurological events measuring intima-media thickness of the
carotid artery or to follow-up aneurism of the abdominal aorta [23].

1.2.4 Multidetector Spiral Computed Tomography Scan

in Geriatric Patients

Computed tomography (CT) is a digital cross-sectional imaging technique that has

undergone a considerable evolution over the past decades. CT scanners have isotro-
pic data acquisition, with the possibility of multiplanar reformations and 3D recon-
structions of the images, which could help depicting complex anatomical structures
and understanding pathological changes [24]. The main advantages of CT are its
wide availability and speed, making it ideal also in emergency settings. Modern CT
scanners, due to their high spatial and temporal resolution, allow to acquire large
volume in few seconds, using 1 mm or less slice thickness. Thus, reducing the risk
of motion and breathing artifacts that could impair the quality of the images, often
relevant in the elderly more than in the adults. Strategies to reduce breathing arti-
facts include a higher pitch and caudo-cranial direction of the scan [25].
1 Imaging Techniques in Geriatric Patients 7

This technique, however, uses higher radiation doses than plain radiographs, but
in this age group the long-term risk of cancer from ionizing radiation is of diminish-
ing concern [25].
CT allows to study in-depth findings already detected on radiography or ultra-
sound, but can also be used directly in case of an important clinical suspicion that
requires a more targeted investigation.
Even though some studies can be performed without the use of contrast media, for
instance for small lung nodules, ureteral stones, or brain after trauma, to improve the
diagnostic evaluation of some pathological conditions, the use of iodinated contrast
agents is mandatory. However, in the elderly, intravascular iodine contrast media
should be used with caution and limited to the indications where it is strictly neces-
sary, in order to reduce the risk of contrast medium-induced nephropathy (CIN) to
which they are more exposed [26]. Geriatric patients usually have a background
reduced kidney function due to age-related functional alterations and tend to be
affected by multiple comorbidities, such as heart insufficiency, hypovolemia, diabe-
tes, and hypertension that could contribute to renal impairment. Moreover, poten-
tially nephrotoxic drugs are used in older adults [27].
When administering iodinated contrast media, the value of serum creatinine must
be evaluated and according to age-appropriate guidelines for contrast agents adminis-
tration, the glomerular filtration (eGFR) rate needs to be greater than 30 mg/mL [25].
Some precautions can be put into practice to reduce the risk of CIN, such as
reduction of quantity of contrast media injected, modifications in kV settings, avoid-
ance of nephrotoxic medications, pre- and post-CT hydration, and in some cases a
sessions of dialysis need to be programmed [26].
Moreover, elderly patients usually have poor peripheral venous access due to frag-
ile vessels; hence, often only small cannulas can be positioned, making them more
susceptible to contrast agent extravasation. Establishing secure intravenous access and
performing a saline test injection may reduce the risk of extravasation [25].
One of the main uses of CT in elderly patients is lung CT, which is able to iden-
tify, even with low-dose protocols, the presence of nodules, masses, or pneumonia
[28]. Coronary CT angiography in the senile population is now considered a useful
diagnostic tool for coronary assessment and risk stratification [29]. A full-body CT
with contrast is often performed for tumor staging, because it offers the possibility
to evaluate lymph node stations and the presence of eventual metastases, in order to
adequately plan the therapeutic approach. Finally, non-contrast brain CT is one of
the main tools used in the elderly, in particular in the emergency setting for stroke
or after trauma [30].

1.2.5 Magnetic Resonance Imaging in Geriatric Patients

MRI is an imaging technique that exploits magnetic fields and radio waves. The
main advantages are the absence of ionizing radiation, the high contrast resolution,
and the direct multiplanar imaging, which make this technique suitable for a wide
range of applications in medical diagnosis [24].

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8 C. Bernetti et al.

Due to the long acquisition times, the need to remain still, and the noisy ambient,
MRI is a difficult imaging technique for elderly patients to tolerate. Moreover, in
case of fragile patients that could require monitoring and, in some conditions, life
support equipment, a MRI room, compared to a CT room is a more difficult envi-
ronment to manage [24].
MRI is also burden by numerous contraindications, many of which are present in
elderly patients, such as claustrophobia, cardiac pacemakers or old ferromagnetic
surgical material. Low-field MRI equipment could be used, at the expense of the
quality of the exam, for patients with claustrophobia or mental health problems,
which would require the use of sedation to tolerate the positioning necessary to
perform high-field MRI [2].
In case of the presence of ferromagnetic material, CT or US must be proposed in
lieu of MRI.
The arrangement of the patient on the scanning table must be as comfortable as
possible; in fact this population is more exposed to develop pressure ulcer if posi-
tioned for long on hard surfaces. Hence, when performing MRI in an older popula-
tion, abbreviated, time-efficient MRI protocol that maintains high diagnostic
accuracy could be useful in order to avoid excessive examination times that are
difficult to bare and could lead to motion and breathing artifacts, but also to avoid
the abovementioned complications.
Limited rapid access to MRI is another limitation that must take into consider-
ation when choosing the right examination for elderly patients.
Even though contrast agents used in MRI are less invasive than the ones utilized
for CT, it remains the risk of nephrogenic systemic fibrosis in patients with poor
renal function, such as elderly. However, in some cases it is a necessary tool, for
instance in the evaluation of neoplasms.
Aging is related to neurodegenerative diseases, dementia, and also stroke, which
represent the main cause of disability and the second cause of death, globally, deter-
mining a high financial and social burden on the healthcare system and society [31].
One of the main use of MRI in the elderly is the study of brain ischemic events,
but it is used also to indagate occult fractures and lesions of the spine [31].

1.2.6 Interventional Radiology (IR) in Geriatric Patients

In the elderly, surgical treatments are a burden because of higher risk of morbidity
and mortality. Interventional radiology offers a less invasive and safer option for the
diagnostic and therapeutic management of many pathologic conditions in this popu-
lation. Another advantage of IR procedures is that it does not require general anes-
thesia, in fact a local approach with eventual deep sedation is often sufficient [5].
The main complications that might occur include infection and bleeding. The imag-
ing methods most used as a guidance for interventional procedures are fluoroscopy,
ultrasonography, and CT, the choice of which is made according to the anatomical
site and type of procedure.
1 Imaging Techniques in Geriatric Patients 9

Many procedures can be performed, such as vascular procedures to treat arterial

stenosis or pseudoneurysm; drainage positioning for ascites, abdominal fluid collec-
tions or abscess; stent or nephrostomy positioning; biliary interventions; vertebro-
plasty; biopsies and thermal ablations [5].

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Neurodegenerative Diseases in Geriatric
Patients 2
Camilla Russo, Rossana Senese, and Mario Muto

Abbreviations

18FDG PET/CT 18F-fluorodeoxyglucose positron emission tomography/com-

puted tomography
AD Alzheimer disease
ALS Amyotrophic lateral sclerosis
ARCA1 Autosomal recessive cerebellar ataxia type 1
Aβ Beta amyloid plaques
BOMBS Brain observer microbleed scale
CAA Cerebral amyloid angiopathy
CBD Corticobasal degeneration
CJD Creutzfeldt–Jakob disease
CNS Central nervous system
CSF Cerebrospinal fluid
CT Computed tomography
DAT Dopamine transporter
DLB Disease with Lewy bodies
DWI Diffusion weighted imaging
EEG Electroencephalogram
ERICA Entorhinal cortical atrophy

C. Russo
Diagnostic and Interventional Neuroradiology, “A. Cardarelli” Hospital, Naples, Italy
Department of Electrical Engineering and Information Technology, Università degli Studi di
Napoli “Federico II”, Naples, Italy
R. Senese
Emicenter European Medical Imaging, Casavatore, Naples, Italy
M. Muto (*)
Diagnostic and Interventional Neuroradiology, “A. Cardarelli” Hospital, Naples, Italy

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 11

G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_2

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12 C. Russo et al.

FLAIR Fluid attenuation inversion recovery

FRDA Friedreich’s ataxia
FTLD Frontotemporal lobar degeneration
FXTAS Fragile X-linked tremor/ataxia syndrome
GCA Global cortical atrophy
HD Huntington disease
MARS Microbleed anatomical rating scale
MCI Mild cognitive impairment
MIRAS Mitochondrial recessive ataxia syndrome
MRI Magnetic resonance imaging
MRPI Magnetic resonance parkinsonism index
MSA Multiple systemic atrophy
MTA Medial temporal atrophy
NBIA Neurodegeneration with brain iron accumulation
NM Nuclear medicine
PD Parkinson disease
PKAN Pantothenate kinase-associated neurodegeneration
PNFA Progressive non-fluent aphasia
PPA Primary progressive aphasia
PrPC Prion protein
PrPSc Scrapie prion protein
PSP Progressive supranuclear palsy
PWI Perfusion weighted imaging
SD Semantic dementia
SPECT Single photon emission tomography
SWI Susceptibility-weighted imaging
VRS Visual rating scales
WMH White matter hyperintensities

2.1 Introduction

Dementia is an umbrella term used to describe a syndrome characterized by deteriora-

tion in cognitive and behavioural functioning not consistent with normal ageing,
severely interfering with daily activities; mild cognitive impairment (MCI), defined as
intellectual decline greater than expected for age but still not interfering with daily
life, can be an early manifestation of dementia. Dementia symptoms include memory
loss, spatial and temporal disorientation, reduced concentration, sleep disturbances,
up to repeated syncope and loss of consciousness, severe autonomic dysfunction, or
behavioural changes including aggressiveness and depression. An early diagnosis can
have a major impact on prognosis and patients’ management, and the prompt identifi-
cation of MCI signs is important to slow down disease progression to overt dementia.
This is even more true considering that cognitive impairment incidence among
the elderly population is rapidly rising. At present dementia affects about 50 million
2 Neurodegenerative Diseases in Geriatric Patients 13

people worldwide, a figure that is expected to double in the next decades due to
population ageing and increasing average life expectancy. Several risk factors have
been called into question for dementia, including sex, ethnicity, educational level,
smoking, drug and alcohol abuse; however, age and genetic factors seem to play a
major role in disease onset and progression [1]. From a clinical perspective, patients
suffering from a neurodegenerative disorder generally realize when their symptoms
began. From here onwards the pattern of cognitive decline is variable, with a period
of relative stability preceding an abrupt and inexorable deterioration. Clinical evolu-
tion speed strictly depends on the putative aetiological mechanism, ranging from
few months in the most aggressive cases to several years in the slowly progressing
diseases [2, 3]. In demented patients, it is supposed to be a certain discrepancy
between actual disease onset and symptoms onset; indeed, due to cellular redun-
dancy in neuronal circuits, symptoms only appear when the number of neurons
spared by neurodegenerative processes is lower than required to maintain a normal
neuronal activity in the affected pathway. Moreover, assuming that the rate of neu-
ronal loss is almost constant during the whole disease course, the observed sudden
clinical deterioration in late-stage dementia is probably due to a collapse in neuron
number beneath a certain threshold [2]. Despite symptom severity, life expectancy
in affected patients is not significantly reduced, unless in case of comorbidities or
direct/indirect involvement of neurological structures responsible for vital functions
(i.e. brainstem centres regulating heart rate, breathing and blood pressure).
The presence of an underlying neurodegenerative process responsible for cogni-
tive decline defines primary dementias. However, severe cognitive impairment is
not only observed in neurodegenerative disorders but also common in vascular,
toxic, paraneoplastic, infectious, metabolic or traumatic insults of the central ner-
vous system (CNS); in these cases, the definition of secondary or potentially revers-
ible dementias may be applied, as some of these conditions may be treatable and
related symptoms partially reversible [4]. Frequently, post-mortem brain examina-
tion represents the only tool for definite differential diagnosis between dementia
types; nevertheless, structural magnetic resonance imaging (MRI) as well as nuclear
medicine (NM) can provide important clues in excluding secondary causes and
hypothesizing the presence of a specific pathogenic mechanism.
This chapter provides a comprehensive overview of the most common neurode-
generative causes of dementia in elderly, classified on the basis of the presumed
underlying pathologic mechanism, focusing on clinical patterns and corresponding
neuroradiological manifestations.

2.2 Neuroradiology and Its Role

in Primary Neurodegeneration

Standardized CNS imaging protocols are crucial in neurodegenerative disorder

assessment, in terms of both first diagnosis and longitudinal follow-up for evaluat-
ing disease progression. Anatomical imaging usually represents the first approach;
MRI and, to a lesser extent, computed tomography (CT) may bring to light
14 C. Russo et al.

structural abnormalities suggestive for a specific disorder; however, despite techno-

logical advances and increased MRI sensitivity, conventional anatomical imaging
can also be unrevealing in early disease stages when clinical symptoms exceed
structural alterations. In these cases, NM metabolic imaging can allow for early
identification of cellular dysfunction even before anatomic alterations onset at MRI
examination [5, 6]. A multimodal algorithmic approach in the evaluation of neuro-
degenerative disorders usually starts with structural MRI and/or CT examination,
first of all to exclude possible mimics such as secondary neurodegeneration (i.e.
vascular dementia, etc.) and surgical pathologies that would benefit of a different
therapeutic approach. Secondly, structural MRI techniques are used to confirm clin-
ical suspicion of primary neurodegeneration by identifying early signs when pres-
ent, or to raise the suspicion of mixed dementia when brain changes suggestive for
more than one dementia type coexist [7]. When anatomical imaging is silent, NM
represents one last option for early dementia characterization and prognostic assess-
ment in doubtful cases. An example of suggested algorithmic approach is shown in
Fig. 2.1.
In terms of method, conventional MRI minimum protocol requires diffusion-­
weighted imaging (DWI) for excluding acute lesions, 3D T1-weighted and/or 3D
T2-weighted imaging for volumetric measurements (with 3D fluid attenuation
inversion recovery—FLAIR—preferred over T2 for white matter lesion burden
assessment), and T2* gradient-recalled echo or susceptibility-weighted imaging
(SWI) for deoxyhaemoglobin, ferritin, haemosiderin and dystrophic calcifications
identification (with SWI up to ten times more sensitive than T2*, as well as able to
differentiate between microbleeds and calcifications); gadolinium-enhanced acqui-
sitions, MR angiography and perfusion-weighted imaging (PWI) are only used
when possible mimics are highly suspected. Among the above-mentioned sequences,
a prominent role is played by MRI volumetric acquisitions that harbour potential for
both qualitative and quantitative atrophy assessments; in particular, quantitative
assessment (carried on with several commercial and open source software) allows
for a more accurate comparison to reference population and regional brain atrophy

Clinical suspicion of cognitive impairment

Evaluation of pseudodementia
and subsequent treatment

Neurological and neuropsychological assessment

Anatomical imaging (brain MRI)

Exclusion of secondary dementia

and surgical pathology

Qualitative/Quantitative assessment of brain atrophy

Qualitative/Quantitative assessment of signal changes

“Silent” imaging MRI highly suggestive

for neurodegenerative disease

Consider metabolic imaging, CSF

Longitudinal brain Diagnostic confirmation
examination, or further investigations in case
MRI follow-up
of significant diagnostic uncertainty

Fig. 2.1 Proposed algorithmic approach for MRI interpretation in dementia

2 Neurodegenerative Diseases in Geriatric Patients 15

patterns’ analysis, also implementing sensitivity to minimal variations in volumes

and reducing inter-rater variability (Fig. 2.2).
Among NM techniques, metabolic imaging with 18F-fluorodeoxyglucose posi-
tron emission tomography/computed tomography (18FDG PET/CT) is used to
assess semi-quantitative cortical glucose uptake, whose metabolism has been found
abnormal in several neurodegenerative disorders such as Alzheimer disease (AD),
Parkinson disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington dis-
ease (HD) [8]. In addition to 18FDG PET/CT, another commonly used second-line
NM modality in case of dementia (especially if coupled to movement disorders) is
represented by dopamine imaging; notably in PD and disease with Lewy bodies
(DLB), dopamine transporter (DAT) single photon emission tomography (SPECT)
examination can be used to assess density of dopamine receptors within the nigro-­
striatal extra-pyramidal pathway, and therefore confirm or exclude the suspected
synucleinopathy [9–11]. Among less diffused NM techniques, the resort to amyloid
precursors for PET/CT imaging (the most well-known is the Pittsburgh compound
B radiotracer) is gaining an over-increasing importance in dementia diagnosis due
to possibility to cross the blood–brain barrier and uniquely bind to beta amyloid
plaques (Aβ); indeed abnormal accumulation of Aβ is a hallmark of amyloid angi-
opathy and even more importantly of AD, the latter representing the most common
form of neurodegeneration in elderly. A new emerging technique similar to amyloid
PET/CT is the tau PET/CT, which might become a further and more specific imag-
ing resource for tauopathies due to the possibility to target and bind tau filaments

a b

Temporal Lobe
Corteccia Ippocampi
Corteccia frontale Corteccia parietale
Percentile: 0.1 temporale
15.30
Temporal Lobe (% of ICV)

Volume 268 ml* 157 ml* 158 ml* 9,3 ml*

14.40 Intervallo normale 226 – 291 ml* 142 – 185 ml* 146 – 183 ml* 8,2 – 10,9 ml*
13.50
95th Percentile normativo 77,8 29,8 30,2 35,6
12.60 75th
50th Corteccia frontale Corteccia parietale
11.70 25th Firma volumetrica
200
5th Ippocampi
10.80 300
180 99 perc.
99 perc.
9.90 250 160
50 perc. 50 perc.
10 perc.140 10 perc.
9.00 1 perc.
1 perc.
200 120
45 48 50 53 56 59 62 65 68 72 74 77 80 83 86 89 92 95
Età 100 Età
150
Corteccia parietale

Corteccia frontale

Age (years) 20 25 30 35 40 45 20 25 30 35 40 45
Corteccia temporale Ippocampi
200 99 perc.
14
180 99 perc. 50 perc.
12 10 perc.
160 50 perc. 99 perc.
10 perc. 10 1 perc.
140 1 perc. 50 perc.
10 perc.
8 1 perc.
120
100 Età 6 Età
20 25 30 35 40 45 20 25 30 35 40 45 Corteccia temporale
Iperintensita in FLAIR

Volume 6,25 ml

* I Volumic cerebrali visualizzati sono normalizzati in base alle dimensioni dell testa. II fattore di correzione per questo paziente è 0,71

Fig. 2.2 An example of automated volume reports from two different commercial software, with
reference to age/sex-matched control population and with cortical atrophy patterns: (a) Icobrain
DM report for MRI (icometrix®) and (b) Quantib Neurodegenerative (Quantib® Brain)
16 C. Russo et al.

and neurofibrillary tangles [12, 13]. However, at present NM is only indicated for
those patients with significant diagnostic uncertainty after a comprehensive multi-
domain evaluation, and when a timely diagnosis may affect patient’s manage-
ment [14].

2.3 Structured Reporting in Primary Neurodegeneration:

Good Practice

As seen above dementia covers a very wide and varied spectrum of possible disor-
ders, whose early differentiation is increasingly gaining importance especially in
light of new emerging treatments and disease-modifying therapies. In this light,
neuroimaging plays a pivotal role both in terms of research and diagnostic purposes.
Therefore a close communication between referring clinicians and radiologists is
strictly required to ensure the capitalisation of all the information provided by imag-
ing techniques. For such purpose, the structured imaging interpretation then trans-
lated in a shared and standardized language is highly recommended [15]; in
particular the introduction of semi-quantitative visual rating scales (VRS) (which
have largely replaced the use of subjective terms), as well as the development of
several software tools to quantify brain atrophy, is simplifying the communication
among professional involved in the care of demented patients [16]. However, despite
the large use for research purposes, brain atrophy quantification with dedicated
tools is still far from an actual application in daily clinical routine due to its limited
territorial diffusion and its cost, process, and time consumption; conversely, the use
of semi-quantitative VRS is widely adopted both in non-academic and academic
institutes [15, 17]. Several VRS were developed to semi-quantitatively assess the
main imaging features of dementia: brain atrophy, white matter micro-vascular
lesion load and cerebral microbleeds burden. Here we summarize the most relevant
semi-quantitative VRS also suggesting a structured interpretation/reporting scheme
to adopt in daily clinical practice.

2.3.1 Brain Atrophy

Brain atrophy is probably the most important hallmark of neurodegeneration sever-

ity. Several semi-quantitative scales have been proposed, and among them the most
used include:

–– Global cortical atrophy (GCA), to assess a general or localized widening of sulci

due to gyral volume loss (Fig. 2.3)
–– Medial temporal atrophy (MTA), to assess hippocampal and mesio-temporal
atrophy (Fig. 2.4)
–– Koedam score, to assess parietal lobe atrophy (Fig. 2.5)
–– Entorhinal cortical atrophy (ERICA) score, to assess the entorhinal cortex for
volume loss (Fig. 2.6)

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2 Neurodegenerative Diseases in Geriatric Patients 17

Volume of sulci Volume of ventricles

Grade 0 Normal No enlargement
Grade 1 Opening of sulci Mild enlargement

Grade 2 Volume loss of gyri Moderate enlargement

Grade 3 Knife blade atrophy Severe enlargement

a b

Fig. 2.3 Scheme of atrophy pattern evaluation by using the global cortical atrophy-frontal (GCA)
score, to be used for each of the individual 13 brain regions assessed separately in each hemi-
sphere; the final score is the sum of all regions. Below, an example of grade 1 (a) and grade 3
(b) atrophy

It should never be forgotten the examination of the infra-tentorial compartment

(always be scrutinized to exclude PSP, MSA, and SCA), by also including qualita-
tive or quantitative measurements (i.e., magnetic resonance parkinsonism index—
MRPI, or midbrain-to-pons ratio) when applicable.

2.3.2 White Matter Lesion Burden

White matter hyperintensities (WMHs) burden on MRI can be easily assessed by

using the Fazekas’ score, a scale based on the visual assessment of number and the
extent of periventricular and deep white matter lesions on axial T2w or T2 FLAIR
images of the whole brain; to each compartment (periventricular and deep white
matter) is given a score from 0 to 3 depending on size and confluence of WMH,
which can then be summed to give a final grading where lower scores indicate lower
lesion burden (Fig. 2.7).
18 C. Russo et al.

Choroid fissure Temporal horn width Hippocampal height

Grade 0 Normal Normal Normal
Grade 1 Minimal enlargement Normal Normal

Grade 2 Mild enlargement Mild enlargement Mild reduction

Grade 3 Moderate enlargement Moderate enlargement Moderate reduction

Grade 4 Severe enlargement Severe enlargement Severe reduction

a b

Fig. 2.4 Scheme of atrophy pattern evaluation by using the medial temporal atrophy (MTA)
score, to assess hippocampal and mesio-temporal atrophy on the coronal plane. Below, an example
of grade 2 (a) and grade 4 (b) atrophy

2.3.3 Cerebral Microbleeds Burden

The quantitative assessment of cerebral microbleeds highly suggestive for CAA on

MRI was first included among the clinical-radiological Boston criteria [18] for the
diagnosis of possible/probable CAA; the number and distribution of haemorrhages
should be assessed on SWI in lobar, cortical, and/or subcortical regions, as well as
on sulci surface (superficial siderosis). More recently two new scales, the Brain
Observer MicroBleed Scale (BOMBS) and the Microbleed Anatomical Rating
Scale (MARS), have been proposed to implement interobserver agreement about
presence, number, size, and location of brain microbleeds; however, their actual
application in daily practice is still limited.

2.3.4 Structured Reporting Checklist

Structured templates for MCI and dementia assessment are used to provide a check-
list within which all relevant items are included and reported; for the sake of com-
pleteness, other key clinical features should always be included at the beginning of
the structured report to complete the general framework.
2 Neurodegenerative Diseases in Geriatric Patients 19

Parietal gyri Parietal sulci

Grade 0 Normal Closed sulcus
Grade 1 Mild cortical atrophy Mild widening

Grade 2 Moderate cortical atrophy Moderate widening

Grade 3 Knife blade atrophy Severe widening

a b

Fig. 2.5 Scheme of atrophy pattern evaluation by using the Koedam score, to assess parietal lobe
atrophy especially on the sagittal and coronal plane. Below, an example of grade 3 atrophy both on
the sagittal (a) and coronal (b) planes

Suggested Checklist:
• Describe the clinical presentation and state the diagnostic suspicion
• Mention the scan protocol used
• Mention previous imaging examination available for comparison
• Exclude possible mimics (mass lesions, hematomas, and any other surgical or
non-surgical disorder that could explain MCI/dementia)
• Exclude the presence of hydrocephalus (communicating or
non-communicating)
• Describe any diffusion abnormality
• Describe vascular pathology (quantification of WMH and microbleeds burden by
using semi-quantitative scales)
• Describe atrophy pattern (symmetric or asymmetric pattern; supratentorial and/
or infratentorial compartment involvement; quantification by using semi-­
quantitative scales)
• Summarize conclusions and final impressions (normal findings according to the
age vs. vascular/neurodegenerative/mixed pathology; pattern consistent with the
clinically suspected dementia disorder; suggest differential diagnosis for
neurodegeneration)
20 C. Russo et al.

Entorhinal cortex Enthorinal cortex

Grade 0 Normal Closed sulcus
Grade 1 Mild cortical atrophy Widening

Grade 2 Moderate cortical atrophy Tentorial cleft sign

Grade 3 Severe atrophy Wide tentorial cleft sign

a b

Fig. 2.6 Scheme of atrophy pattern evaluation by using the entorhinal cortical atrophy (ERICA)
score, to assess the entorhinal cortex for volume loss. Below, an example of grade 2 atrophy on 3D
T1w (a) and 3D FLAIR (b) images; dotted line indicates the entorhinal cortex, white arrowhead
indicates the enlargement collateral sulcus (with only minimal detachment of the entorhinal cortex
from the cerebellar tentorium, also known as “tentorial cleft sign”)

Fazekas score for WMHs

Grade 0 None or isolated punctate WMH lesion
Grade 1 Multiple WMH lesions

Grade 2 Initially confluent WMH lesions

Grade 3 Largely confluent WMH lesions

a b c d

Fig. 2.7 White matter hyperintense (WMH) lesion burden evaluated by using Fazekas’ score on
axial FLAIR MRI. (a) grade 0, (b) grade 1, (c) grade 2, (d) grade 3
2 Neurodegenerative Diseases in Geriatric Patients 21

2.4 Most Common Primary Neurodegenerative Disorders

in Elderly and Neuroradiological Clues for Diagnosis

The overall number of neurodegenerative disorders runs into the hundreds and some
of them overlap clinically or pathologically, making the differential diagnosis quite
challenging. As noted above, two main factors contribute to this phenomenon: on
the one hand a same neurodegenerative disease can affect different areas of the
brain, which leads to a large phenotypical variability specially in early disease
stages; on the other hand some disorders share some common features, thus resem-
bling one another in some clinical manifestations [19, 20]. In terms of classification,
primary neurodegenerative disorders can be classified according to brain abnor-
malities location, clinical manifestations, or pathological mechanism. Following
this last criterion here we give a short overview of typical findings and neuroradio-
logical hallmarks of the most common neurodegenerative disorders in the elderly.
The three most significant groups are represented by:

–– Tauopathies—defined by the presence of intracellular tau-positive inclusions in

the human brain, formed by neurofibrillary tangles generated by the hyperphos-
phorylation of a microtubular protein (called tau) that induce the protein to dis-
sociate from microtubules and form insoluble aggregates
–– Synucleinopathies—defined by the abnormal deposition of aggregates of alpha-­
synuclein (a protein involved in synaptic vesicle trafficking and neurotransmitter
release) within neurites, axons and glial cells, interfering with normal DNA
repair function
–– Amyloidosis—defined by the presence within grey matter of neurotoxic amyloid
plaques (or Aβ plaques), due to aberrant extracellular deposits of the amyloid
beta protein (arising from the amyloid-beta precursor protein, a synaptic cell
surface receptor regulating iron uptake and neuronal plasticity).

As final remarks, in both tauopathies and amyloidopathies, it is thought that the

abnormal formation of misfolded insoluble oligomers may induce other molecules
to assume the same misfolded structure, then causing protein aggregation and depo-
sition in a sort of “cascade-effect” similar to the one observed in prion infection;
however, the aetiopathogenesis of these disorders has not yet been fully elucidated.
Moreover it should be noted that this arbitrary classification does not take into
account the co-occurrence of some of these dementing disorders in a same patient,
a phenomenon that can be at least in part attributed to a certain overlap in patho-
genic mechanisms (i.e. AD and CAA) [21].

2.4.1 Tauopathies

2.4.1.1 Alzheimer Disease (AD)

AD is the most common type of dementia, with prevalence increasing from 1%
between 60 and 65 years to about 30–40% over 85–90 years of age. Overall AD is
22 C. Russo et al.

thought to be responsible for about 60–80% of all overt dementias, with an age-­
specific prevalence that almost doubles every 5 years in subjects aged >65 years.
This exponential increase in AD prevalence in elderly suggests that AD strictly
related to ageing, therefore considered the main risk factor; however, apart from
ageing, other risk factors have also been described (including family history of
dementia, female gender, apolipoprotein E epsilon 4 allele carrier status, smoking
and mutations in the amyloid precursor protein) [22].
As per other forms of dementia, also in AD the neuropathological changes due to
amyloid and tau deposition (leading to the formation of plaques) occur up to
25–30 years before clinical manifestations. From a clinical standpoint we can there-
fore observe a long silent (or pre-clinical) phase, followed by an overt progressive
neurodegenerative disorder (starting when a certain neurotoxicity threshold has
been exceeded). Clinical symptoms include memory loss and MCI in early stages,
then followed by decline in praxis and visuo-spatial abilities, attention deficit and
behavioural changes (with neuropsychiatric symptoms ranging from apathy, depres-
sion and anxiety up to aggressiveness, psychomotor agitation and psychosis). Apart
from AD classical variant initially characterized by anterograde episodic memory
loss, two other clinical (or atypical) variants may be identified: frontal variant AD
(fvAD) and posterior cortical atrophy (PCA). In both cases the same neuropatho-
logical changes of AD can be observed in the brain, however with different spatial
distribution and thus causing different symptoms at onset. In fvAD, the condition
mainly affects frontal lobes, with dominance of behavioural changes, executive dys-
function or a combination of both over a pure memory loss. In PCA early manifesta-
tions are related to visual cortex involvement, with symptoms including difficulty in
recognising faces, measuring distances and perceive the surrounding space; due to
this insidious onset, PCA variant may be difficult to identify and it can take a long
time before considering the proper diagnosis.
Moving to imaging in AD patients, although CT is able to detect atrophy, MRI is
the golden standard to describe the pattern of cortical atrophy and exclude possible
differential diagnoses. Atrophy typically occurs first in hippocampus, perirhinal and
entorhinal cortex, prior to pervasive progression to diffuse cortical atrophy; this
atrophy can be assessed by observing the enlargement of the parahippocampal fis-
sures, or alternatively by using MTA and/or ERICA scores. Medial temporal lobe
atrophy is found both in AD and (to a lesser extent) in other primary neurodegenera-
tive disorders, whereas it is less commonly observed in normal ageing; however,
despite a certain specificity, such volume loss does not appear early in the course of
the disease, thus representing only a late AD manifestation. Posterior cortical atro-
phy or bilateral frontal lobe atrophy are observed in later AD stages coupled to
medial temporal lobe involvement, or in atypical AD variants (PCA and fvAD) as
an early finding coupled to a relative sparing of the medial temporal lobe. In addi-
tion to the above features, WMH due to chronic small vessel disease, cerebral
microbleeds and microinfarcts can also be observed; in these cases, the simultane-
ous vascular and neurodegenerative pathologies double the risk and exacerbate the
symptoms of dementia. Apart from conventional imaging, functional MRI also har-
bour the potential to show a reduced activation in hippocampus and related
2 Neurodegenerative Diseases in Geriatric Patients 23

structures within the medial temporal lobe of AD patients, either during cognitive
paradigms or resting state; similarly, different advanced techniques such as diffu-
sion tensor imaging, quantitative susceptibility mapping and magnetization transfer
have also been used for analysing the damage in the same structures. However at
present these applications have only been exploited for research purposes and used
by limited number of research groups, therefore far from clinical widespread appli-
cations [23].
Structural MRI can be complemented by a variety of NM examinations in case
AD is suspected, both for supporting the diagnosis (even before symptoms onset)
and stratifying the prognosis (in case of overt dementia). SPECT and FDG-PET are
used to detect regional hypoperfusion and hypometabolism, respectively, generally
with a bilateral and symmetric temporo-parietal, precuneus and posterior cingulate
distribution; sensorimotor cortex is generally spared, whereas frontal lobes are usu-
ally involved in later disease stages. Diagnostic specificity can also be increased by
resorting to amyloid-PET and tau-PET; amyloid and tau biding tracers selectively
accumulate in grey matter and medial temporal lobes respectively, with amyloid
deposition occurring before tau deposition. In particular, amyloid binding tracers
are used as a negative predictor of AD, as the absence of captation makes the diag-
nosis unlikely. Conversely tau-binding tracers are not specific for AD, as they are
found positive also in other tauopathies; however, the higher is the accumulation
within hippocampus, entorhinal cortex and temporoparietal cortex, the more severe
is the AD cognitive decline. Therefore we can conclude that, while Aβ plaques
should be considered a disease biomarker, tau-positive inclusions mainly represent
a progression-related biomarker.

2.4.1.2 Corticobasal Degeneration (CBD)

CBD is a rare and probably underestimated tauopathy, with a peak incidence
between the fifth and seventh decade of life and a slight male prevalence. Despite
CBD is generally diagnosed as a sporadic disorder, rare familiar and isolated genetic
cases have also been described; in the familiar forms, CBD has been associated with
mutations in genes encoding for progranulin or microtubule-associated protein tau.
Tau-positive inclusions in CBD are mainly disseminated within motor cortex (pre-
motor, supplementary motor and somatosensory), basal ganglia and brainstem.
Clinical manifestations reflect this distribution, even if the global clinical picture
often overlaps with other neurodegenerative disorders with subsequent diagnostic
challenges. CBD generally starts as an asymmetric, akineto-rigid syndrome with
apraxia, dystonia, myoclonus and postural instability, unresponsive to levodopa;
cognitive impairment and behavioural changes can also be observed in early disease
stages, frequently associated to the alien limb phenomenon.
Asymmetric clusters of grey matter atrophy in specific regions invariably charac-
terize MRI findings in CBD, mainly involving bilateral thalami, bilateral posterior
fronto-median and cingulate cortex, bilateral premotor and supplementary motor
area, and middle frontal and precentral gyrus; regional atrophy in frontal, parietal,
temporal and occipital lobes can also be found. Left hemisphere is generally more
affected; however, right-sided features of CBD can also be occasionally observed.
24 C. Russo et al.

The most affected cerebral hemisphere is also characterized by the presence of

WMH on T2/FLAIR images within subcortical and periventricular white matter
[24]. Research studies concerning the use of volumetric cluster analysis and diffu-
sion tensor imaging for CBD characterization are still ongoing, and suitable clinical
applications have not yet been developed. NM only plays a marginal role in CBD at
present, with SPECT and PET studies showing asymmetric metabolic changes in
the same areas of atrophy on MRI; among these techniques, tau-PET probably has
the larger potential for monitoring disease status, disease progression and therapeu-
tic targeting monitoring.

2.4.1.3 Frontotemporal Lobar Degeneration (FTLD)

FTLD in an umbrella term used to describe different dementing disorders with
prominent behavioural and language deterioration. Most common as a sporadic dis-
ease, at present FTLD recognizes a genetic determinant in 20% cases; most com-
mon mutations involve the progranulin and microtubule-associated protein tau
genes (similar to the one described for CBD), but also C9ORF gene (with a certain
pathogenic overlap with motor-neuron disorders involving the same genetic locus).
Despite the partial understanding of its aetiology and despite its clinical heterogene-
ity, FTLD can be grouped in three main subtypes based on the proteinaceous inclu-
sions observed at pathological examination: FTLD-Tau in case of misfolded tau
protein; FTLD-TDP in case of transactive response DNA binding protein 43;
FTLD-FUS in case of fused sarcoma protein. Most of FTLD subtypes belong to the
first group; compared to other tauopathies, FTLD has the peculiarity to affect
younger patients (50–60 years) at onset and to have a slower clinical progression.
From a clinical perspective, FTLD can be divided in two macro-categories
according to clinical presentation: behavioural variant frontotemporal dementia
(bvFTD) and language variant frontotemporal dementia (lvFTD, also known as pri-
mary progressive aphasia—PPA). bvFTD has a predominant frontal lobe involve-
ment, while lvFTD has a predilection for the temporal lobe and is further divided
into several subtypes: non-fluent variant primary progressive aphasia (nfvPPA), also
named progressive non-fluent aphasia (PNFA); semantic variant primary progres-
sive aphasia (svPPA), also named semantic dementia (SD); and the rare logopaenic
variant primary progressive aphasia (lvPPA).
Imaging features described in these forms of dementia largely overlap one
another [25], and only limited differences in atrophy patterns can be identified at
qualitative evaluation. bvFTD is mainly characterized by changes in social behav-
iour and poor impulse control, while memory is generally spared and language dis-
ability generally present; in this variant at MRI examination atrophy is confined to
mesio-frontal, orbito-frontal and anterior temporal cortices, with a typical anterior-­
to-­posterior gradient and with the associated enlargement of anterior horns of the
lateral ventricles. PNFA is characterized by poor speech production; in this case,
atrophy is limited to bilateral insulae and inferior frontal gyri at the level of Broca’s
area. SD is characterized by poor language comprehension with preserved speech
abilities; at MRI a severe anterior temporo-polar atrophy can be observed, usually
more marked in the dominant hemisphere, associated with a variable hippocampal

AL GRAWANY
2 Neurodegenerative Diseases in Geriatric Patients 25

atrophy. Finally, lvPPA is a disturbance in thinking of the words to use while speak-
ing, narrow attention span, progressive hesitation and difficult comprehension of
complex sentences; on MRI this variant is characterized by a selective left temporo-­
parietal atrophy. Metabolic studies with FDG-PET confirmed the presence of hypo-
metabolic areas corresponding to atrophic cortex, with a pattern completely
superposed on the one observed at MRI examination.

2.4.1.4 Progressive Supranuclear Palsy (PSP)

PSP is a rare tauopathy of unknown aetiology, which manifests as an atypical par-
kinsonian syndrome. PSP shows a strong male predominance (8:1), with a mean age
at onset of approximately 65 years and an overall prevalence of about 5:100,000;
median survival after symptoms onset is about 6–8 years, with death frequently
occurring because of complications due to brainstem damage.
Clinical PSP onset can be insidious, with axial motor abnormalities, gait instabil-
ity and frequent falls as common initial manifestations; as the disease progresses,
worsening parkinsonism, dysarthria, dysphagia, sleep disturbance and personality
changes due to frontal cognitive decline can be observed. Unlike it might be thought,
eye movement abnormalities (notably supranuclear ophthalmoplegia, which is con-
sidered the hallmark of PSP) only appear later during disease progression.
Depending on the prevalence of brainstem or cortical feature, we can distinguish
several clinical PSP variants: classic progressive supranuclear palsy or Richardson
syndrome (PSP-RS), progressive supranuclear palsy-parkinsonism (PSP-P), pro-
gressive supranuclear palsy-pure akinesia with gait freezing (PSP-PAGF), progres-
sive supranuclear palsy-corticobasal syndrome (PSP-CBS), progressive supranuclear
palsy-behavioural variant of frontotemporal dementia (PSP-bvFTD) and progres-
sive supranuclear palsy-progressive non-fluent aphasia (PSP-PNFA).
MRI in PSP diagnosis is poorly sensitive in early stages, with peculiar features
only appearing in more advanced disease; conventional MRI is helpful in demon-
strating midbrain atrophy with secondary third and fourth ventricle enlargement,
fronto-temporal, pontine and cerebellar atrophy, as well as T2w signal increase
within the inferior olives and the periaqueductal grey matter. In particular, midbrain
atrophy results in the so-called hummingbird sign (flattening of the superior aspect
of the midbrain on the sagittal plane) and morning glory sign (loss of the lateral
convex margin of the tegmentum on the axial plane at mammillary body level);
when midbrain atrophy is more pronounced, the so-called mickey mouse appear-
ance of the brain stem on the axial plane (defined as a reduction in the anterior-­
posterior midline midbrain diameter at the level of the superior colliculi greater than
12 mm) can also be observed. These qualitative features are inconstant and depen-
dent from the adopted acquisition planes; therefore, quantitative measurements are
considered more sensitive. There are two main options to assess midbrain atrophy
on MRI, the MRPI and the midbrain-to-pons area ratio, both helpful in distinguish-
ing PSP from other movement disorders. MRPI is obtained by measuring the width
of the superior cerebellar pedicle on the coronal plane, the middle cerebellar pedicle
on the sagittal plane and the area of the midbrain and pons on the sagittal plane, then
by multiplying the pons area to midbrain area ratio by the middle cerebellar
26 C. Russo et al.

peduncle width to superior cerebellar peduncle width ratio; a value of more than 14
is highly suggestive for PSP. A recent version called MRPI2.0 also included ven-
tricle enlargement in the computation, with a final figure obtained by multiplying
the MRPI by the ratio of third ventricular width to frontal horn width; however,
these computations can suffer from inter-rater variability and limited reproducibil-
ity. Therefore easier techniques, such as the above-mentioned midbrain-to-pons
area ratio, should be preferred. The area of the midbrain and pons are calculated on
the midline sagittal plan at the level of ponto-mesencephalic and ponto-medullary
junctions; in PSP patients, this parameter is significantly reduced or even halved,
while in PD MSA and healthy brain is approximately 0.24. An example of MRI
findings in PSP is shown in Fig. 2.8. Functional imaging studies are not entirely
specific for PSP; it has been described that FDG-PET can show hypometabolism in
the frontal lobe and/or midbrain, while I-123 ioflupane SPECT may demonstrate
loss of the normal crescent-shaped tracer uptake in the striatum.

a b c

Fig. 2.8 Most prominent MRI features of PSP: atrophy of the midbrain with the hummingbird
sign on sagittal images due to preserved pontine volume (a, black arrow), associated to cerebellar
atrophy and periacqueductal grey matter hyperintensity (b, black arrowheads); mickey mouse
appearance of the brain stem on the axial plane (c); midbrain-pons ratio <0.12 (d)
2 Neurodegenerative Diseases in Geriatric Patients 27

2.4.2 Synucleinopathies

2.4.2.1 Disease with Lewy Bodies (DLB)

DLB is the second most common synucleinopathy after PD, and the second most
common neurodegenerative dementia after AD; it accounts for about 15–20% of all
cases of neurodegenerative dementia, with an average age at diagnosis of 65 years.
The pathologic hallmark of DLB is the abnormal accumulation of intracellular
Lewy bodies (namely eosinophilic cytoplasmic inclusions whose primary structural
component is represented by the alpha-synuclein protein). The underpinning genetic
abnormalities are still unknown.
DLB clinical presentation is characterized by progressive memory loss, attention
deficit, visual hallucinations, gait disturbances, rigidity and slowed movements,
with additional manifestations that may also include sleep disorders and behav-
ioural changes; from a clinical standpoint, to some extent DLB may resemble to AD
or PD dementia, thus raising a problem related to differential diagnosis. At present
genetic and laboratory findings do not contribute to solve this caveat, with the dis-
tinction made even harder to apply due to the lack of specific findings also at con-
ventional imaging. Indeed MRI sequences show no pathognomonic sign, with the
only remarkable findings represented by little hippocampal and posterior regions
atrophy; on SWI the absence of the swallow tail sign (the normal imaging appear-
ance of nigrosome-1 within the substantia nigra on axial susceptibility weighted
images) is also considered a sensitive marker for both DLB and PD with high posi-
tive predictive value; however, it is generally visible only in late disease stages. In
this setting, DAT scan may give a significant contribution to DLB differential diag-
nosis, showing deficient dopaminergic presynaptic transport in substantia nigra and
striatum not consistent with AD; this deficient uptake generally results in a bilateral
dot sing, instead of the normal bilateral comma-shaped appearance.

2.4.2.2 Multiple Systemic Atrophy (MSA)

MSA is a sporadic rare neurodegenerative disorder and one of the most well-­
recognized synucleinopathies; it has an overall prevalence of 3:100,000, with a
median age at onset of approximately 66 years and a median survival time of 8 years
from initial diagnosis. MSA is characterized to a variable extent by cerebellar
ataxia, autonomic dysfunction, parkinsonism and corticospinal dysfunction. We can
distinguish two main clinical forms of MSA, the one with predominantly parkinso-
nian signs (MSA-P) and the one with predominantly cerebellar signs (MSA-C),
depending on the prevalent non-autonomic symptoms observed. Such symptom
variability is related to the sites within the brain where neurons and glial cells are
more affected by abnormal alpha-synuclein intracellular deposition, respectively,
striatonigral pathway in MSA-P or olivopontocerebellar circuits in MSA-­
C. Parkinsonism, rigidity, postural instability and gait disturbance are typical of
MSA-P, whereas ataxia, loss of movement coordination, tremor and nystagmus are
typical of MSA-C. Degeneration of autonomic nuclei in the brainstem resulting in
autonomic failure (more frequently urogenital and cardiovascular disorders) is an
28 C. Russo et al.

almost constant finding in both the variants; in more advanced phases sleepiness,
dysphonia, dysphagia, dystonia and excruciating pain can also occur.
MSA can be suspected based on clinical and neuroimaging findings. For MSA-P,
the most reliable sign on conventional MRI is represented by putaminal atrophy,
with relative central hypointensity on T2* images due to iron accumulation and
peripheral hyperintensity on T2w images due to reactive astrogliosis. Conversely, in
MSA-C the most evocative signs are represented by severe isolated atrophy of cer-
ebellum and brainstem (especially olivary nuclei and middle cerebellar peduncle)
coupled to a cruciform signal hyperintensity in the central pons known as hot cross
bun sign (due to the selective degeneration of transverse pontocerebellar fibres and
median pontine raphe nuclei with relatively spared corticospinal tracts) (Fig. 2.9).
Although specific for MSA-C, hot cross bun sign only appears in case of advanced
disease progression. Among NM techniques, I-123 ioflupane SPECT is usually nor-
mal in these patients. In recent times, the identification of new PET radiotracers as
well as the resort to diffusivity analysis coupled to automated volume loss quantifi-
cation on volumetric MRI acquisitions have been proposed as a tool for distinguish
MSA from other synucleinopathies and from tauopathies; however, these studies
are still embryonic and far from clinical widespread application [26].

2.4.2.3 Parkinson Disease (PD)

Also known as idiopathic parkinsonism, PD is a neurodegenerative synucleinopathy
whose onset is characterized by movement disorder with the triad resting tremor,
rigidity and bradykinesia; it accounts for about 80% of all parkinsonian syndromes,
with a peak age at onset of 60 years. Although PD usually starts as a movement
disorder, it can progress to dementia over time, with manifestations involving

a b

Fig. 2.9 Most prominent MRI features of MSA-C: severe isolated atrophy of cerebellum
and brainstem on the axial (a) and coronal (b) planes; diffuse ex vacuo dilated cerebellar folia (a,
black arrow), associated with a mild cruciform signal hyperintensity in the central pons (a, white
arrowhead)
2 Neurodegenerative Diseases in Geriatric Patients 29

cognitive and behavioural domains. PD pathogenesis is related to the progressive

degeneration of dopaminergic neurons within the substantia nigra (pars compacta),
with symptoms appearing when 80% striatal dopamine is depleted. The aetiology of
PD is still largely unknown, with more than 30 genetic risk loci identified till now;
indeed, only a minority of all PD cases recognize a monogenic cause (rare familiar
and juvenile variants), whereas the large majority of cases is sporadic and character-
ized by genetic complexity.
PD is responsive to dopaminergic drugs (i.e. apomorphine and levodopa) and
deep brain stimulation; therefore, its early and accurate diagnosis is crucial for opti-
mal patients management and monitoring. Initial imaging findings are subtle and
inconstant, requiring an appropriate examination and an accurate interpretation to
be identified. The most relevant MRI feature is the loss of the normal swallow tail
appearance on axial SWI at the level of substantia nigra pars compacta (reported
diagnostic accuracy of about 90%), with or without a mild hyperintensity on T1w of
substantia nigra and red nuclei due to abnormal iron accumulation; non-specific dif-
fuse cerebral volume loss can also be observed (Fig. 2.10). Also in this case DAT
scan can be used to confirm the diagnostic pattern of PD, especially in patients with
uncertain clinical diagnosis. Abnormal DAT scan in PD shows a marked loss of the
normal comma-shaped or crescent-shaped tracer uptake in the striatum; a differen-
tiation between PD and atypical parkinsonism is be possible by using different trac-
ers [27].

2.4.3 Cerebral Amyloid Angiopathy (CAA)

CAA is a relatively common clinical entity in the elderly detected in approximately

10–30% of elderly brains, with a prevalence estimated to rise from about 2% at
65 years to 12% in subjects over 85 years; in addition pathological hallmarks of
CAA have been found in about 80% with AD and 40% with CAA present with AD

a b c

Fig. 2.10 Most relevant MRI features of PD: partial loss of the normal swallow tail appearance
on axial SWI at the level of substantia nigra pars compacta (a, white arrow) coupled to mild T2w
signal alteration on the coronal plane (b); no significant atrophy is observed in the supratentorial
compartment (c)
30 C. Russo et al.

symptoms during their lives. This significant overlap between CAA and AD must be
framed in the common presence of amyloid deposits in brain tissue; in CAA such
insoluble oligomers deposition is mainly found in blood vessel primarily at the level
of smooth muscle cells, but also in pericytes and endothelial cells. It was hypothe-
sized that amyloid produced by neurons is drained along the perivascular spaces
within brain parenchyma up to the abluminal portion of the tunica media, the sur-
rounding smooth muscle cells and in the adventitia, where it deposits under specific
conditions thus causing diffuse angiopathy [28].
Generally sporadic and occasionally found as a familiar disorder, CAA is a pos-
sible cause of MCI and dementia; cognitive impairment in this setting can be both
gradual (due to a vascular dementia caused by lobar cerebral microhaemorrhages
and ischemic leukoencephalopathy) or rapidly progressive (in case of recurrent
haemorrhages or inflammatory angiopathy).
At MRI the two primary features of CAA are represented by microbleeds and
WMH (more or less confluent depending on the severity of ischemic leukoencepha-
lopathy and generally sparing subcortical fibres), where the relation between micro-
bleed burden and cognitive impairment severity is known to follow an exponential
trend. Cerebral microbleeds are defined as perivascular deposits of haemosiderin
from millimetric micro-haemorrhages, usually located at grey–white matter junc-
tion or in the cerebellum but sparing basal ganglia and pons; microbleeds can be
distinguished only on T2* sequences as small foci of blooming artefact, with SWI
up to 10 times more sensitive than other T2* images. Other possible findings also
include lobar or cerebellar haemorrhages (that tend to spare the basal ganglia and
pons), convexity subarachnoid haemorrhage and/or superficial siderosis (as a
chronic manifestation of previous convexity subarachnoid haemorrhages, both
symptomatic or asymptomatic), dilated perivascular spaces at the level of centrum
semiovale and corona radiate, and microinfarcts or ischemic lacunae (due to acute,
subacute or chronic ischemic insult).

2.4.4 Others

2.4.4.1 Creutzfeldt–Jakob Disease (CJD)

Spongiform encephalopathy encompasses a group of rare neurodegenerative disor-
ders occurring in adult patients and in the elderly, characterized by rapid neuropsy-
chiatric decline, cerebellar/extrapyramidal dysfunction and fatal outcome (generally
within 1 year from symptoms onset). Among spongiform encephalopathies, CJD
represents the most frequent disorder, with a peak onset between 60 and 75 years;
in the large majority (80–90%) of cases, CJD is sporadic (sCJD) although familial,
zoonotic and iatrogenic forms have also been described. The triggering event in
CJD pathogenesis is the structural and conformational conversion of a naturally
existing prion protein (PrPC) into a misfolded and protease-resistant form named
scrapie prion protein (PrPSc), able to initiate a catalytic conversion of wild-type
PrPC into PrPSc (where the aberrant PrPSc is the mould for the pathological con-
version of more PrPC); in this pathologic process, the normal synthesis of PrPC
2 Neurodegenerative Diseases in Geriatric Patients 31

within brain tissues provides an over increasing substrate for this cascade effect. At
histological examination, the counterparty of these events is the pathological depo-
sition of amyloid plaques within normal brain tissue, coupled to the vacuolization
of neutrophil and normal myelin. Depending on molecular markers observed in
affected patients, sCJD can be further divided into subtypes based on two elements:
the amino acid at codon 129 in the prion protein gene (subtype MM if methionine,
VV if valine, or MV if both) and the size of the protease-resistant core of the abnor-
mal prion protein (subtype 1 if 21 kDa, 2 if 19 kDa or 1 + 2 if both PrPSc types).
sCJD diagnosis relies on the combination of clinical features coupled to the
results in one or more para-clinical tests among electroencephalogram (EEG), cere-
brospinal fluid (CSF) analysis and/or MRI. EEG is generally aspecific, with the
most evocative patterns of alteration only observed in late disease stages. CSF anal-
ysis is probably the most sensitive supportive examination, allowing for the detec-
tion of a specific protein called 14-3-3 (whose expression is correlated to sCJD with
a sensitivity and a specificity of >90%). However MRI abnormalities still represent
the most important hallmark for CJD, with alterations visible even before or in case
of unremarkable findings at EEG and CSF examination [29].
Most common MRI alterations are represented by symmetric or asymmetric, dif-
fuse or focal restriction of water diffusion associated to a less marked increase in
T2-FLAIR signal within cortical and deep grey matter. The aetiology of DWI
abnormalities is still poorly understood, probably related to compartmentalization
within myelin vacuoles or to abnormal deposition of prion protein somehow restrict-
ing free water diffusion. The most typical patterns involve insula, cingulate cortex,
superior frontal gyrus, striatum and thalamus (generally with anterior → posterior
gradient); peri-rolandic cortex, pulvinar and cerebellum are usually (but not invari-
ably) spared. Usually cortical and deep grey matters are both affected, with the
exception of VV1 subtype prominent cortical involvement (almost completely spar-
ing deep grey matter) and of MV2/VV2 exclusive basal ganglia involvement with
very limited/absent cortical abnormalities (Fig. 2.11). Cerebellar atrophy can also
be observed, especially in later CJD stages.
The intensity of the T2-FLAIR equivalent depends on disease severity and dura-
tion; moreover, if NM is performed, the areas of restricted water diffusion and ele-
vated T2-FLAIR signal correspond to PET/CT areas of hypometabolism. MRI
features are therefore crucial in case of sCJD clinical suspicion, supporting the diag-
nosis when typical imaging patterns are observed and possible mimics ruled out,
thus guiding the approach to EEG/CSF interpretation.

2.4.4.2 Huntington Disease

HD is an autosomal dominant trinucleotide repeat syndrome due to the expansion of
CAG (cytosine-adenine-guanine) trinucleotide in the gene encoding for a protein
called huntintin located on chromosome 4, abnormally amplified to >35 copies
(compare to the normal value <26 copies); the larger is the number of copies the
more severe is the disease course, with a progressively earlier onset and a more
rapid clinical deterioration. Moreover HD appears at an earlier age in descendants
of affected patients, a phenomenon called genetic anticipation that is due gene
32 C. Russo et al.

a b c

Fig. 2.11 Three possible patterns of signal alteration in sCJD (first row DWI sequences, second
row FLAIR sequences): usual asymmetric basal ganglia involvement with mild DWI restriction of
frontal cortex (a); more unusual bilateral and symmetric basal ganglia involvement (b); rare selec-
tive cortical involvement (c)

instability during cell division caused by the abnormal number of these repeats;
generally the trinucleotide repeats expand until the gene stops functioning.
Huntingtin protein has a prominent role in protein trafficking, vesicle transport,
synaptic (i.e. dopaminergic) signalling and neural cells apoptosis; therefore, its loss
or toxic gain of function is responsible for premature neurodegeneration due to
disruption in many intracellular pathways.
Being HD characterized by an autosomal dominant pattern of inheritance with
complete penetrance, the probability of transmitting the mutated gene is 50% and
all the individuals with the pathologic allele express the clinical phenotype. Although
most serious presentation is generally observed in young adults, HD can also be
diagnosed in elderly in case of short CAG expansion, with the highest recorded
prevalence ranging between 60 and 69 years; in these cases, atypical parkinsonism
as well as cognitive or psychiatric disturbances are the first manifestations, with
chorea and deficit in postural control appearing later on in more advanced stages
(MCI described up to 15 years before motor symptom onset) [30].
Due to the pervasive impact on dopaminergic circuits, HD is mainly character-
ized by the loss of GABAergic neurons within basal ganglia, especially in caudate
2 Neurodegenerative Diseases in Geriatric Patients 33

and putamen nuclei; this neuronal loss is responsible for the most typical HD imag-
ing feature at MRI, characterized by focal atrophy and secondary enlargement of
frontal horns of the lateral ventricles (with increased frontal horns width to intercau-
date distance ratio or intercaudate distance to inner table width ratio). Indeed it has
been demonstrated that striatal atrophy is positively correlated with disease severity
and negatively correlated with the number of CAG triplet repeats. Besides the stria-
tum, extra-striatal atrophy can also be observed in thalamus, hypothalamus, globus
pallidus, limbic system and cerebellum; occasional findings may also include iron
deposition within basal ganglia on SWI and increased T2w signal of the putamen.
In preclinical HD as well as in case of atypical clinical presentation with poor motor
symptoms, FDG-PET showing striatal hypometabolism or DATscan showing
decreased striatal dopamine transporter binding may support MRI findings is guid-
ing the genetic diagnosis.

2.4.4.3 Sporadic Adult-Onset Degenerative Ataxia

Apart from MSA-C, other hereditary or non-hereditary degenerative ataxias can be
responsible for sporadic adult-onset degenerative ataxias. Among the hereditary
forms, the following are most frequently associated to a later onset >60 years:
Friedreich’s ataxia (FRDA), an autosomal recessive disorder due to the abnormal
expansion of GAA triplet (guanine-adenine-adenine) in the FXN gene encoding for
the protein frataxin, required for normal mitochondrial function within neural tis-
sue; autosomal recessive cerebellar ataxia type 1 (ARCA1) due to mutations in
SYNE1 gene, required for the synthesis of a protein responsible for the homeostasis
in Purkinje cells of the cerebellum; fragile X-linked tremor/ataxia syndrome
(FXTAS), observed in older (>58 years) pre-mutation carriers of FMR1 gene
(55–200 CGG—cytosine-guanine-guanine repeats), leading to neuronal toxicity
and mitochondrial dysfunction (with women less affected than men because of the
second X chromosome); mitochondrial recessive ataxia syndrome (MIRAS) caused
by mutations of the POLG1 gene encoding the mitochondrial DNA polymerase
gamma enzyme. When neither genetic nor acquired causes of late-onset ataxia can
be identified, it applies the definition of non-hereditary sporadic adult onset ataxia
(or idiopathic late-onset cerebellar ataxia), which further requires epidemiological
and genetic studies to fully elucidate the unknown underlying pathogenic mecha-
nism. However, both the hereditary and non-hereditary forms share the most rele-
vant MRI features, including a constant and marked cerebellar atrophy coupled to a
variable T2/FLAIR signal alteration within cerebellar lobes, cerebellar pedicles and
dentate nuclei; the simultaneous involvement of cerebral white matter, thalamus and
corpus callosum is inconstant, whereas brain atrophy is observed with varying
degrees in most cases [31, 32].

2.4.4.4 Late-Onset Neurodegeneration with Brain Iron

Accumulation (NBIA)
NBIA encompasses heterogeneous group of rare neurodegenerative disorders due
to abnormal brain iron deposition, with variable neurological deficits including
extrapyramidal symptoms and neuropsychiatric disturbances. At present an over
34 C. Russo et al.

increasing number of putative genes has been identified, with variable phenotypical
and MRI presentation depending on the specific causative mutation. Generally
affecting children or young adults, NBIA can also be occasionally observed in
elderly population; in these unusual cases, the most common manifestation is repre-
sented by a late-onset atypical parkinsonism. When clinical suspicion is raised,
MRI and DATscan are required to identify typical findings as well as to rule out
PD. The most common NBIA in the elderly is represented by pantothenate kinase-­
associated neurodegeneration (PKAN) [33], whose most remarkable MRI feature is
represented by T2w hypointensity within globus pallidi and substantia nigra (cor-
responding on SWI/T2* to susceptibility artefacts due to abundant iron deposition)
with a central hyperintense spot due to myelin vacuolisation (also known as “eye of
the tiger” sign); on spectroscopy, decreased N-acetylaspartate and increased myo-
inositol levels can be observed due to neuronal depletion. Other possible NBIAs,
such as aceruloplasminaemia or neuroferritinopathy, are only exceptionally
observed.

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Neurovascular Emergencies in Geriatric
Patients 3
Giuseppe Maria Di Lella, Luca Ausili Cefaro,
and Cesare Colosimo

3.1 Introduction

“Neurovascular emergencies” represent an ample concept that comprehend not only

the classical concept of “cerebrovascular disease,” in which resides the ischemic
and hemorrhagic arterial stroke, the effect of the cerebral venous thrombosis, and
the causes of subarachnoid hemorrhage (SAH), but also the bleedings related to
head trauma, such as the epidural and subdural hematomas. It is of common knowl-
edge that cerebrovascular disease alone represents the third more common cause of
death in the developed world and the first cause of disability in the adult population.
In fact almost half of the patients do not regain the normal physical abilities and
need long-term assistance from both their family and the healthcare systems. These
concepts are much more important in the elderly, due to the higher incidence of
specific risk factors, like high blood pressure, atherosclerosis, and, regarding the
specific problems related to traumatic hemorrhages, the anatomical predisposition
of the old people to experience various type of falls. The rate of stroke event doubles
each 10 years after the age of 55 years, making clear how the vast majority of
lesions occur in this group. Considering the progressive increase of elderly in the
population of the developed countries, this kind of pathologies has an increasing
social impact and need to be addressed in the best possible way. More disturbing is
the fact that cerebrovascular disease, and in particular stroke, is increasing globally.
The future does not look very bright considering that by 2050 the population aged
over 65 years is expected almost to triple; in effect the percentage of the population
over the age of 65 years is steadily increasing and is expected to continue in the
foreseeable future, with people over the age of 80 years now among the fastest

G. M. Di Lella · L. Ausili Cefaro · C. Colosimo (*)

Department of Radiological Sciences, Fondazione Policlinico Universitario A. Gemelli
IRCCS, University of the Sacred Heart, Rome, Italy
e-mail: [email protected]; [email protected];
[email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 37

G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_3
38 G. M. Di Lella et al.

growing subset of the population. Effective management of patients who have cere-
brovascular disease depends on accurate diagnosis. The neuroradiological studies
and treatments play a major role in the diagnosis and treatment of patients often
affected also by other age-­related symptoms and pathologies (i.e., dementia, diabe-
tes, etc.). The wide diffusion, in the last two decades, of high-quality CT and MRI
systems has allowed better and faster anatomic and functional evaluation, or exclu-
sion, of ischemic and hemorrhagic lesions of arterial or venous origin, especially
with the availability of fast and reliable CT and MR perfusion techniques. The
“need of speed” in these often uncooperating patients is in fact of paramount impor-
tance in order to achieve a proper diagnosis. Neuroradiology plays an established
role also in the therapeutic phase, due to the continuous advance of the materials
and techniques available (i.e., flow diverter stent in the treatment of aneurysms).
Technological advancements have led to advanced interventions such as angio-
plasty, stenting, and carotid endarterectomy for selected stroke patients and
expanded access to acute stroke services through tele stroke programs. In the past
decade, we have also enhanced our understanding of the mechanisms of brain
injury, repair, plasticity, and recovery that hopefully will improve our future post
stroke treatments. In the United States from 1997 to 2007, the stroke death rate fell
44.8%, and the actual number of stroke deaths declined 14.7%, making stroke the
fourth instead of the third leading cause of death.

3.2 Ischemic Stroke

Stroke is the fifth leading cause of death among elderly persons in the United States
[1]. While stroke can occur at any age, ischemic stroke is predominantly a disease
of the elderly, as age is the most substantial nonmodifiable risk factor. Stroke risk
increases with age, and in 2009, 66% of persons hospitalized for stroke were
65 years or older. The growing longevity of human populations and the associated
multimorbidity explain how the number of accidental strokes is projected to double
between 2010 and 2050, with most strokes occurring in adults over the age of
75 years [2]. Additionally, this age group (>75 years) experiences more hospitaliza-
tion stays and higher mortality post-stroke. Over 80% of strokes result from isch-
emic damage to the brain due to an acute reduction in the blood supply. Around
25–35% of strokes present with large vessel occlusion, and the onset of patients in
this category is often characterized by severe neurological deficits [3, 4].
Stroke is a complex disease that can be caused by multiple potential etiologies;
it is really a heterogeneous disorder with more than 100 pathologies implicated in
the pathogenesis. However the end result is mostly represented by the occlusion of
an artery, which almost immediately leads to hypo perfusion of the tissue segment
supplied by that vessel; the affected parenchyma usually consists of a severely hypo
perfused (cerebral blood flow [CBF] ≤10 mL/100 g/min) central infarct core where
the damage is irreversible. It is bordered by the critically hypo perfused (CBF
10–20 mL/100 g/min) ischemic penumbra (tissue-at-risk), where the injury may be
reversed if timely reperfusion occurs. Collaterals aim at preserving as much
3 Neurovascular Emergencies in Geriatric Patients 39

penumbral tissue as possible. With time (minutes to hours) the infarct core expands
at the expense of the penumbra. This is also helped by the mass effect of the edema-
tous tissue on the neighboring arteries. The penumbra is surrounded by other
involved tissue, which is not at risk of infarction, the so-called benign oligemia
(CBF >20 mL/100 g/min) [5] (Figs. 3.1 and 3.2).
Stroke imaging (CT and/or MR) is crucial in the handling of such patients and
has to be performed in a fast and efficient manner; early diagnosis and assessment
are important in the treatment of acute ischemic stroke (AIS). The main roles of
imaging are: exclude an intracranial hemorrhage, define the ischemic region, distin-
guish between infarct core and penumbra, and finally depict the vessel status. In
particular:

–– Nonenhanced computed tomographic (CT) imaging represent the first imaging

step and is regularly used to exclude hemorrhage (classically detected as a lesion
with high CT density, 60–90 HU) and other diseases, and indicate early changes
in AIS, such as obscuration of the lentiform nucleus/insular ribbon, due to the
loss of the normal slight hyperdensity over the surrounding white matter struc-
tures following the onset of cytotoxic edema, hyperdensity of the feeding artery,

a b c

f
d e

Fig. 3.1 Right occipital ischemic stroke. A 75-year-old woman with visual disturbance (hemi-
anopsia). FLAIR (a), T2 (axial and coronal; b, e), and DWI (d) show the classic appearance and
MR imaging of an acute infarct in the PCA territory, with hyperintensity in the cortex and subcorti-
cal white matter of the right deep occipital lobe. Angio-TOF sequences (c) and T1 C+ MR (f)
confirm the presence of a right P2 segment occlusion
40 G. M. Di Lella et al.

a b c

d e f

Fig. 3.2 Left temporal-parietal ischemic stroke. A 71-year-old man with aphasia and sudden right
hemiparesis; classic appearance of an early subacute cerebral infarct. Axial CT scan (a) in the ER
show a low-density area with loss of SB/SG differentiation and swollen appearance of the involved
temporo-parietal cerebral convolutions; axial MIP view of the CTA (b) shows normal cerebral
intracranial district (“circle of Willis”). MR FLAIR axial and DWI (c, f) and T2 coronal TSE (d)
obtained 48 h after the initial onset of speech difficulties demonstrate an area of hyperintensity in
the same region, associated with hyperintensity in DWI images, due to typical diffusion restriction
in the acute phase (within 7 days). Angio-MRI (TOF 3D, e) confirms the normal parity of arterial
circulation of the base of the skull

loss of the gray–white matter interface, and swelling of the cerebral tissue. The
Alberta Stroke Program Early Computed (ASPECTS) is a CT score system that
can be used to quantify the extent of ischemia: 10 brain regions are assessed
dichotomously for the presence (or not) of early signs of ischemic stroke, result-
ing in a range 0–10, with 1 point subtracted for any evidence of early ischemic
change in each region defined on the CT scan; baseline CT showing a large area
of hypo attenuation is considered as an indicator of poor outcome (ASPECTS <7).
–– Hypo perfusion abnormalities can be accurately measured using perfusion CT
(PCT) and MR perfusion-weighted imaging (PWI); these are able to define the
area of irreversible severe ischemia, with complete loss of oxygen and glucose
supply and resultant depletion of energy stores, cellular necrosis, and cavitation
(“ischemic core”) and also the area surrounding the ischemic core, characterized
3 Neurovascular Emergencies in Geriatric Patients 41

by moderate ischemia and cellular dysfunction but not cell death, which is poten-
tially reversible with prompt reperfusion (“ischemic penumbra”). Perfusion CT
(PCT) is one of the best imaging techniques readily available in an emergency
room to evaluate acute stroke patients for the presence, quantity, and distribution
of the ischemic penumbra, through a dynamic technique involving sequential CT
data acquisition [6] in suspect brain areas during an intravenous bolus injection
of iodinated contrast medium. The most relevant and used parameters are: cere-
bral blood flow (CBF), cerebral blood volume (CBV), average transit time
(MTT), time-to-peak (TTP). In the ischemic penumbra, cerebral perfusion is
impaired, but self-regulation is preserved; vasodilation and collateral recruitment
lead to an increase in CBV. Quantification of ischemic “core” (CBF <30%) and
estimation of “penumbra” or tissue at risk (T-max >6 s) can provide immediate
information for treatment decision-making. Clinical trials have shown that perfu-
sion mismatch ratios of core/penumbra greater than 1.8 may indicate the eligibil-
ity for endovascular treatment (EVT) [7, 8].
Some institutions have MRI available anytime and prefer it over CT, when the
patient’s condition permits, because of the additional information it provides.
Diffusion-weighted magnetic resonance imaging (MRI) is the most useful
method for detecting hyper acute ischemia and the “ischemic core” while PWI,
in selected cases, could be used to evaluate hypo perfusion abnormalities. MRI
can detect abnormal cytotoxic edema (this restricted diffusion areas are seen as
bright on b1000 DWI images and with low signal on the corresponding automati-
cally calculated apparent diffusion coefficient [ADC] maps) in the early stage
and show clear discrimination between ischemic lesions and normal brain tissue.
After the acute phase of decreasing ADC to the lower value, at 1–4 days, the
ADC subsequently rises and “pseudo normalizes” to transient equivalence with
normal brain tissue (although the tissue is infarcted), typically at 1–2 weeks, and
keeps rising until the ADC values would result elevated in the chronic stage [9].
Since the signal intensity on DWI depends on ADC as well as the T2 information
inherent in the b = 0 echo-planar image, net hyper intensity on the DWI images
may be due to low ADC or T2 effects: the “T2 shine-through.” The DWI-FLAIR
mismatch depends on the lack of marked parenchymal hyper intensity on fluid
attenuated inversion recovery (FLAIR) on early MRI study and has been used as
an MRI parameter to widen the treatment window, with intravenous bolus of
r-TPA, in patients with AIS with onset of symptoms beyond 4.5 h and/or in case
of unknown onset time, as in the “wake-up” stroke. Neuroimaging methods, par-
ticularly MRI, based on PWI parameter and DWI lesion volumes, may allow us
to identify the ischemic penumbra and predict brain tissue viability in patients
with AIS, although criteria to define clinically relevant mismatch are not yet
standardized [10] (Fig. 3.3).
–– Obviously the evaluation of intracranial arterial vessels and collateral circula-
tion, made possible through this kind of imaging modalities, is of paramount
importance and is achieved by CT or MR angiography. The study should cover
the entire arterial tree, from the aortic arch to the vertex. MRI provides the advan-
tage of noncontrast imaging of the intracranial arteries using the flow-sensitive
42 G. M. Di Lella et al.

a b c d

e f g h

Fig. 3.3 CT, CTA, CTP, and MRI evaluation in the left MCA territory stroke. Normal appearing
non-contrast CT scan in the ER of a 76-year-old female with sudden onset of aphasia (a). Axial
MIP view of the CTA (b) shows a distal left MCA occlusion, while CT perfusion (c, d) shows an
infarct, with core–penumbra mismatch in the left MCA territory. Non-contrast CT obtained 48 h
after initial onset of speech difficulties (e) shows the classic appearance of an early subacute cere-
bral infarct. Note the wedge-shaped, low-density area involving both the gray and white matter in
the left MCA distribution and in the left thalamus. Follow-up MRI with axial DWI (/ADC) image
(f, g) and FLAIR (h) in the same patient show hyperintensity in the same region within the left
MCA territory. The DWI hyperintensity is due to true diffusion restriction, typical in the acute
phase (within 7 days)

time-of-flight (TOF) technique. Multiphase or dynamic CTA represents the fast

scanning protocols and is timed to optimize the acquisition in the arterial phase,
an independent predictor of radiological and clinical outcomes in patients with
AIS [11]. CTA provides information of arterial, capillary, and venous phases of
cerebral arteries. Thus the radiological report should comment upon: (a) site of
occlusion; this is of utmost importance since large vessel occlusions produce
severe neurological symptoms and eventually result in poor outcomes; and (b)
details of collateral circulation, which are of paramount importance, since the
extent of collateralization is a predictor of final infarct volume and thus the clini-
cal outcome. The collateral circulation plays a crucial role in the pathophysiol-
ogy of ischemic stroke and is closely related to the treatment response and the
patient’s prognosis [12]. The presence of good collateral circulation helps to sus-
tain the penumbral area and increase the rate of successful reperfusions [13]. It
was shown that the rate of neuronal loss varies greatly depending on the state of
the collaterals, which can maintain a stable penumbra for several hours after the
onset of occlusion (Fig. 3.4).

AL GRAWANY
3 Neurovascular Emergencies in Geriatric Patients 43

a b c

d e f

Fig. 3.4 Artery occlusion in a right temporal ischemic stroke. A 71-year-old man with confu-
sional state and sudden onset of left hemiparesis. CT axial documents tenuous right temporo-polar
hypodensity with initial loss of SB/SG differentiation (a). CTA demonstrates the occlusion of the
M1 segment of the right middle cerebral artery (b); note the hyperdensity of the horizontal section
of the rACM on the basal images (a). The CT follow-up after 6 h shows a better defined area of
low-density, with loss of SB/SG differentiation and swollen appearance of the temporo-insulare
cerebral convolutions involved (d). MR axial DWI and T2 coronal TSE confirm the lesion, repre-
sented by an area of T2 hyperintensity in the same region, associated with hyperintensity in DWI
images, due to typical diffusion restriction in the acute phase (within 7 days, c, f). Angio-TOF
sequences document re-habilitation of the right M1 segment of the ACM (e)

Treatments involve implementing strategies to obtain the reperfusion of the “at

risk” brain tissue and are based on intravenous and intra-arterial administration of
thrombolytic drugs and the application of various thrombectomy devices during
angiographic procedure and fluoroscopic guidance (the approved devices have dif-
fering mechanisms of action: clot retrievers, aspiration device, and stent retrievers).
Intravenous thrombolysis with intravenous recombinant tissue Plasminogen
Activator (r-tPA; Alteplase) represents the “standard of care” drug in the case of an
acute ischemic stroke. This treatment improves functional outcomes and is more
effective if the administration begins in a very early phase of the stroke. Intravenous
44 G. M. Di Lella et al.

recombinant tissue plasminogen activator (r-tPA) remains the standard of care for
patients with moderate to severe neurological deficits who present within 4.5 h from
symptom onset (Acute Ischemic Stroke [Study ECASS-3] and the American Heart
Association/American Stroke Association [AHA/ASA]).
Treatment with intravenous thrombolysis has been tested using imaging bio-
markers to select patients with unknown stroke time onset. These biomarkers com-
prise either penumbral imaging (i.e., perfusion-diffusion MRI or perfusion CT) or
MRI-based tissue-clocking—i.e., the mismatch between a visible ischemic lesion
on diffusion weighted imaging (DWI) and lack of marked parenchymal hyper inten-
sity on fluid attenuated inversion recovery (FLAIR) on MRI (termed DWI-FLAIR
mismatch). The results of recent trials (EXTEND, ECASS4-EXTEND and
EPITHET) have shown, in fact, that patients with ischemic stroke 4,·5–9 h after
stroke onset or with wake-up stroke with evidence of salvageable brain tissue using
CT perfusion or perfusion-diffusion MRI, who were given intravenous Alteplase,
have improved functional outcomes compared with those given placebo. The “ben-
efit to risk” ratio seems to be larger in patients who meet automated perfusion mis-
match criteria [14].
Outcomes for some patients with acute ischemic stroke and moderate to severe
neurological deficits due to proximal artery occlusion are improved with endovas-
cular reperfusion therapy. Efforts to hasten reperfusion therapy, regardless of the
mode, should be undertaken within organized stroke systems of care [15]. It is also
suggested that the EVT should not just be held back based on age, and even patients
over the age of 80 years can benefit from EVT. In conclusion, studies recently dem-
onstrated statistically that endovascular treatment (EVT) combined with intrave-
nous thrombolysis (IVT) has good efficacy and high safety in the treatment of acute
intracranial arterial occlusion, and the combination can significantly improve the
patients’ quality of life, therefore having a high clinical application value [16].

3.3 Nontraumatic Intracranial Hemorrhage

Hemorrhagic conditions should be separated into intracerebral hemorrhage (ICH)

and subarachnoid hemorrhage (SAH). These two subtypes of hemorrhage have dif-
ferent causes, different clinical findings, and different treatment strategies.

3.3.1 Intracerebral Hemorrhage (ICH)

Nontraumatic intracerebral hemorrhage (ICH) results from bleeding into the brain
parenchyma arising from the rupture of an arterial vessel, most often (>80%) a
small arteriole affected by cerebral small vessel diseases (SVD).
Stroke is the second leading cause of death worldwide, and one of the leading
causes of disability. ICH is the second most common subtype of stroke after isch-
emic stroke and accounts for approximately 10–20% of all strokes [17, 18]. A large
meta-analysis recently concluded that most likely the incidence of intracerebral
3 Neurovascular Emergencies in Geriatric Patients 45

hemorrhage has not changed between 1980 and 2006, but consistent across the vari-
ous studies was the finding that the incidence of intracerebral hemorrhage increased
strongly with age, with persons aged 85 years and over having an almost tenfold
increase in yearly risk of intracerebral hemorrhage. Overall case fatality at 1 month
for ICH is reported as 40%. ICH outcomes have been well described in the general
population, but there is a paucity of data regarding complications and outcomes in
the “very elderly” (age >80 years). Available data suggest that patients >85 years
have an almost tenfold increase in yearly risk of ICH compared to patients aged
45–54 years. As the population ages, the incidence of ICH in the very elderly will
likely increase, and the number of Americans aged >65 years is projected to more
than double by 2060 [19, 20].
More than 50% of primary ICH events are directly correlated with hypertension
as a risk factor, whereas ≈30% are known to be associated with cerebral amyloid
angiopathy (CAA). Deep perforator arteriopathy is linked with hypertension
(though not exclusively) and is a frequent cause of nonlobar or deep ICH in the
basal ganglia or brainstem but also contributes to lobar hemorrhage (Fig. 3.5).
CAA is caused by amyloid beta deposition in cortical and leptomeningeal blood
vessels and is a major contributory cause of lobar ICH. Other ICH risk factors are
genetic factors, diabetes, alcohol intake, smoking, oral anticoagulant treatment,
drug abuse, and older age. Intracerebral hemorrhage can occur as a complication of
a preexisting lesion, such as vascular malformation or tumor, which is then referred
to as secondary intracerebral hemorrhage (15–20%) [21–23].
The clinical presentations of ICH and ischemic stroke are similar, typically con-
sisting of abrupt onset of a focal neurologic deficit. Decreased level of conscious-
ness, vomiting, headache, seizures, and very high blood pressure (BP) might suggest
the presence of ICH. However, none of these symptoms/signs is specific enough to
distinguish hemorrhagic from ischemic stroke [24].
Intracerebral hemorrhage is therefore a life-threatening medical emergency that
requires timely diagnosis; brain imaging is essential to reliably distinguish ICH
from ischemic stroke, usually with a rapid noncontrast CT (NCCT) which is highly
sensitive for all forms of acute intracranial hemorrhage, is a fast technique, with
excellent sensitivity, also in noncooperative patients, to identify acute ICH, and
given its wide availability is considered the gold standard for the diagnosis of ICH
in the ER departments. Beyond the diagnosis of ICH, NCCT can provide useful ele-
ments such as ICH location, intraventricular extension, hydrocephalus, presence
and degree of edema, and midline shift or brainstem compression secondary to the
mass effect from the hematoma. Moreover, NCCT allows to quantify the volume of
a hematoma and determine its approximate age, by evaluating the density of the
lesions, measured in Hounsfield units (HU), according to the value of X-ray attenu-
ation corrected for the attenuation coefficient of water; HU for water is equal to 0,
blood is between 30 and 45, gray substance is between 37 and 45, white substance
is between 20 and 30, whereas bone is between 700 and 3000. On CT, an acute ICH
typically presents as a hyper dense mass within the brain parenchyma showing
Hounsfield Units (HU) of 50–70. Within 1–6 weeks, the ICH becomes isodense
(=“subacute” ICH) typically showing a decrease of attenuation of 1.5 HU a day.
46 G. M. Di Lella et al.

a b

c d

Fig. 3.5 “Typical” primary hemorrhage in the right lentiform nucleus. A 72-year-old man with
hypertension and ASA therapy, the axial non-contrast CT study in ER shows the classic appear-
ance of an acute hemorrhage in the R basal ganglia involving the putamen and external capsule
(striatocapsular), with minimal surrounding edema, without significant mass effect (a). CTA, in the
coronal plane, shows mild displacement of the lenticulostriate arteries. There is no spot sign that
would indicate active bleeding. No underlying vascular lesion was found (b). Follow-up MRI with
axial T1 TSE (c) and coronal T2 TSE (d) shows the physiological evolution in the early subacute
phase of the striatocapsular hemorrhage, due to transformation in intracellular methemoglobin

“Chronic” ICHs present as a hypodense mass compared to the surrounding brain

parenchyma [25, 26]. CT angiography (CTA) or MR angiography are appropriate
initial investigations to detect macrovascular bleeding sources. Initial diagnostic
accuracy studies (comparing acute noninvasive angiography with the gold standard,
3 Neurovascular Emergencies in Geriatric Patients 47

digital subtraction angiography) suggested high specify and sensitivity. Contrast-­

enhanced CTA performed <96 h from symptom onset has a high accuracy for pre-
dicting underlying vascular anomalies, with sensitivities ≥95% and specificities
approaching 100%. Positive and negative predictive values have also been reported
to be in excess of 97% [27–29]. A comprehensive diagnostic workup of ICH etiol-
ogy is needed in ICH survivors to inform patients and relatives about the risk of
recurrence as well as strategies for secondary prevention. MRI is superior in detect-
ing markers of SVD including white matter lesions, lacunas, perivascular spaces,
cerebral micro bleeds, cortical superficial siderosis, and atrophy. A comprehensive
workup of ICH etiology should, therefore, include an MRI in the days/weeks fol-
lowing the acute ICH event including T2/FLAIR, DWI, SWI/T2* and contrast-­
enhanced sequences, as well as MR angiography [30, 31] (Fig. 3.6).
ICH patients should ideally be treated in a comprehensive hospital environment,
involving a multidisciplinary organization team comprising neurology, neurosur-
gery, neuroradiology, intensive care, emergency medicine, and internal medicine,
possibly being admitted to a stroke unit, in order to constantly monitor the patient’s

a b c d

e f g h

Fig. 3.6 “Typical” intra-axial hemorrhage in the left thalamus. A 72-year-old woman with sudden
right loss of strength and dysarthria. Axial CT study in ER show a small hyperacute hemorrhage in
the left thalamus with minimal surrounding edema (“typical” intra-axial hemorrhage, a). Axial CT
at 24 h demonstrates huge increase of the blood collection and the mass effect, with extension of
the bleeding in the ventricular system, also in the fourth ventricle (not shown) (b). The subsequent
CT angiography did not show arterial or venous malformations, but demonstrated further enlarge-
ment of the hematoma (d). Follow-up MRI with angio-TOF sequences at 1 month (and CT, c)
evidentiate size reduction of the collection, due to the disappearance of surrounding edema and
physiological evolution of the blood components: hemosiderin in the periphery (black ring) and
mostly deoxyhemoglobin in the core (e–g). No vascular malformation was found on the TOF
angiographic sequence (h)
48 G. M. Di Lella et al.

vital parameters and reduce/eliminate the factors that determine ICH (modifiable
factors), with stabilization of blood pressure, suspension/reduction of anticoagulant
drugs, and possibly administration of prothrombotic drugs. The role of surgical
therapy remains controversial and surgical evacuation of supratentorial hematomas
should be considered only as a lifesaving measure in deteriorating patients. The
only condition in which there is consensus in favor of surgical intervention is in
cerebellar hematomas with clinical or imaging signs of hydrocephalus and/or brain-
stem compression. In these cases, surgical decompression and hematoma evacua-
tion should be performed as soon as possible in the vast majority of cases [32, 33].

3.3.2 Subarachnoid Hemorrhage (SAH)

Subarachnoid hemorrhage (SAH) is defined as blood in the cerebrospinal fluid con-

tained in the basal cisterns and the sub-arachnoid space of the cerebral hemispheres,
between the arachnoid mater and the pia mater [34].
Subarachnoid hemorrhage (SAH) is a potentially fatal disease that mainly affects
middle-aged patients, with a mean age of 60 years [35, 36]. Yet, due to better gen-
eral health and improved life expectancy, the number of hospital admissions of
elderly SAH patients is constantly increasing; recently, the annual incidence of
SAH in persons aged 70 years was estimated to exceed 25/100,000. The incidence
of aneurysmal subarachnoid hemorrhage (aSAH) is known to rise with age, espe-
cially in women. Both the number of elderly patients with aSAH and the total inci-
dence have therefore been estimated to be increasing. In addition to the characteristics
of elderly aSAH, such as a high rate of poor clinical grade on admission, severe
aSAH on initial computed tomography (CT) scan, and general complications, the
most serious problem is a high rate of poor outcome. In particular, several studies
indicate that poor outcome significantly increases in the patients over age 75 years.
The death rate in patients increases with age [37, 38] (Figs. 3.7 and 3.8).
Subarachnoid bleeding usually occurs rapidly over several seconds. In some
patients, it is preceded by a “warning headache,” or minor bleeding, several days or
weeks ahead of the major rupture. The major SAH episode presents as the sudden
onset of severe, usually diffuse, headache, which patients describe as the “worst
headache of their life”; vomiting, cessation of activity, and decreased level of con-
sciousness are frequently present. Ruptured aneurysms are the cause in 85% of
patients, whereas 10% fit into the pattern of so-called nonaneurysmal perimesence-
phalic hemorrhage, a relatively innocuous condition. The remaining 5% are caused
by various rare causes (arteriovenous malformations that abut on pial surfaces can
bleed. Amyloid angiopathy, severe hypertension, bleeding disorders, drugs, and
occult trauma are among the less frequent causes) [34, 39, 40].
Diagnosis centers on defining the presence of an aneurysm or other bleeding
lesion. CT and MRI of the brain are highly sensitive tests for detecting acute
SAH. CT scanning is the first investigation if subarachnoid hemorrhage is sus-
pected. The ability to detect subarachnoid hemorrhage is dependent on the amount
of subarachnoid blood, the interval after symptom onset, the resolution of the
3 Neurovascular Emergencies in Geriatric Patients 49

a b c d

e f

Fig. 3.7 Ruptured ACA saccular aneurysm in a 74-year-old male. (a) Non-contrast CT scan in ER
at 11 am: widespread, bilateral, and symmetrical subarachnoid hemorrhage secondary to the rup-
ture of an ACA saccular aneurysm. The lesion location was suspected on the non-contrast CT due
to the higher blood density in the lamina terminalis cistern and confirmed with the CT angiography
(b–d). (e, f) DSA, before and after embolization with GDC coils, done on the same day. Note the
complete lesion occlusion and consequent exclusion from the intracranial arterial circulation.
Everything went well, apparently, with progressive albeit partial diappearance of the onset symp-
tomatology, …

scanner, and the skills of the radiologist. If performed within the first 2 days of
SAH, CT scans have 95–100% sensitivity for intracranial hemorrhage. This sensi-
tivity diminishes to 85% within 5 days, 50% after 1 week, 30% after 2 weeks, and
0% after 3 weeks [41–43].
Other than the positive diagnosis of SAH, the initial CT examination can detect
the early complications of hydrocephalus, intraparenchymal hematoma with space
occupying effect and ventricular hemorrhage. Hydrocephalus, which begins with
dilatation of the temporal horns, and a compressive intra-parenchymal hematoma
need to be diagnosed and reported, as they represent life-threatening conditions and
require immediate neurosurgical treatment with the positioning of an external ven-
tricular shunt and/or the evacuation of the hematoma before the treatment of the
cause of the SAH (Fig. 3.9).
Relying on CT of the brain to make a diagnosis of SAH after 1 week is instead
an uncertain and much more challenging affair. Because of the greater availability
and feasibility of CT imaging in patients with suspected subarachnoid hemorrhage,
few studies of MRI in the acute phase after subarachnoid hemorrhage have been
reported. These suggest that in the first few hours and days, MR with proton density
and, nowadays almost exclusively, FLAIR images is as sensitive as CT imaging.
After the initial days, when hyperdensity on CT scans decreases, MR is better for
detecting blood, with fluid attenuation inversion recovery (FLAIR) and T2* images
being the most sensitive techniques [42, 43]. Vascular imaging, usually including
cerebral dye contrast angiography, is needed. CT angiography (CTA) of the circle
50 G. M. Di Lella et al.

a b c

d e f

g h i

Fig. 3.8 (a–i) …but 11 days after the treatment the patient’s history became the “worst case sce-
nario” in a clinical case like this, with the onset of an almost untreatable vasospasm, followed by
multiple ischemic lesions, intraparenchymal bleeding partially along the ventricular catheters, and,
finally, an infectious cerebritis with massive vasogenic edema and ventricular hypertension, that
led this unfortunate patient, a MD Radiologist by the way, to the exitus. This case would be a
reminder that nowadays subarachnoid hemorrhage also represents, also in a “not so old” individ-
ual, a life threatening occurrence, not only at the onset, but also after a routinary successful treat-
ment of the primary lesion

of Willis has a sensitivity of 98% to detect intracranial aneurysms, particularly

because of its excellent spatial resolution, which is less than 1 mm. CTA in general
is useful not only to identify one or more aneurysms as potential causes in a patient
with subarachnoid hemorrhage but also to study the anatomical configuration of the
aneurysm in relation to adjoining arteries, which allows optimum selection of treat-
ment (coiling/stenting or clipping) and, therefore, the choice between the surgical or
intravascular approach. CT angiography is a continuously improving technique.
The sensitivity for detecting ruptured aneurysms, with conventional angiography as
the gold standard, is currently about 95% [44, 45] (Fig. 3.10).
3 Neurovascular Emergencies in Geriatric Patients 51

a b

c d

Fig. 3.9 Severe hydrocephalus in ruptured PCoA aneurysm (a, b). Non-contrast CT study in ER
of a 81-year-old woman with severe headache and consciousness alteration shows diffuse sub-
arachnoid hemorrhage (SAH) throughout the basal cisterns and massive intraventricular hemor-
rhage. Note the enlargement of both temporal horns of the lateral ventricles, consistent with early
hydrocephalus. SAH was caused by a ruptured saccular aneurysm located in the PCoA segment of
the right internal carotid artery (not shown). (c, d) Non-contrast CT after the endovascular embo-
lization of the aneurysm and placement of an atrial-ventricular catheter for the treatment of intra-
cranial hypertension
52 G. M. Di Lella et al.

a b c

d e f

Fig. 3.10 Endovascular treatment in an SAH from a saccular L Pcom ruptured aneurysm. A
74-year-old woman with sudden, severe headache. Axial CT study in ER shows extensive sub-
arachnoid hemorrhage (SAH) throughout the basal cisterns and intraventricular hemorrhage
(left>right). Note the enlargement of both temporal horns of the lateral ventricles, consistent with
early hydrocephalus (a, b). Cerebral angiography demonstrates the presence of a saccular Pcom
aneurysm of the left internal carotid artery, which most likely represents the cause of the bleeding
(c). Unsubtracted images during coiling of the aneurysm with balloon assistance for the neck cov-
erage (f). Axial CT after the endovascular embolization of the aneurysm shows an ample parenchy-
mal ischemic area (in the left frontal and parietal regions) due to SAH-related vasospasms, with
mild mass effect and compression of lateral ventricles (d, e)

The appropriate treatment of this disease in elderly patients, predominantly

regarding the occlusion of the ruptured intracranial aneurysms, is still controversial.
About 5% of all strokes are due to SAH, and about 10% are due to ICH, depending
on age, sex, educational and social status, and racial composition of the evaluated
patients. Treatment of patients harboring aneurysms is aimed at eliminating the aneu-
rysm’s rebleeding potential either by direct surgical clipping or coating or by endo-
vascular techniques that contain and thrombose the aneurysmal sac. In the latest
years in particular has been developed a new “stenting” method to allow the exclu-
sion of an aneurysmal sac from the cerebral circulation. After some unsatisfactory
attempts with coated stent, in order to cover the aneurysm’s origin from the parent
vessel, the results of several new hemodynamic studies, allowed by the availability of
new ultrafast volumetric CT scanner, with up to 320 slices contemporary acquisition,
drew attention to the fact that the aneurysmal growth was largely dependent on the
peculiarity of the flowing blood, both in the parent vessel and, as a consequence, in
the aneurysmal sac [46, 47]. A new kind of stents with “flow diverting” features was

AL GRAWANY
3 Neurovascular Emergencies in Geriatric Patients 53

therefore developed, which, distorting the local hemodynamic, eliminates the exces-
sive pressure inside the lesion, which suddenly shrinks and could finally disappear.
As a result of these continuous evolution, the percentage of aneurysm malforma-
tions that require a conventional surgical approach has been greatly diminished and
is currently limited to the cases in which the endovascular treatment is not feasible,
due to the patient’s vascular anatomy that could not allow the catheter navigation, or
the complexity of the aneurysm origin, with close relationship with adjacent vessel
that needs to be savaged.
In elderly especially, the endovascular approach has the great advantage of being
much less invasive and therefore more sustainable from often more fragile individu-
als. On the other hand, the vessels are often tortuous, with calcifications and some-
time accompanying stenosis, which in some cases do not allow the catheter to reach
a proper position in order to release the devices (stent and/or coils), required from
the treatment [48–50].

3.4 Traumatic Intra-axial Brain Injures (TBI)

Traumatic brain injury (TBI) is among the leading causes of death and disability
worldwide, with enormous negative social and economic impacts. Traumatic cerebro-
vascular injury (TCVI) is a common pathologic mechanism of traumatic brain injury
with often possible multiple intracranial lesions (Fig. 3.11). Among the elderly, in
recent years, instances of neurotrauma have been increasing [51]. As aged population
grow, so the instances of traumatic brain injury (TBI) in the elderly are increasing. It
has been known that the frequency curve of TBI by age groups has two peaks, in
patients at 15–29 and 65–79 years of age [52]. In recent years, this curve has changed
and currently shows a single peak, only in the elderly age range, resulting from both
decreased frequency in the young and increased frequency in the elderly. In addition,
the peak of frequency in the elderly is continuously shifting toward older ones. Such
changes may be the result of the increased representation of aged individuals in the
population, as well as the reduction in traffic injures, by far more common in the
young people. Age has been proposed as one of the most reliable prognostic factors
following TBI. Both survival and functional outcomes are significantly poorer in the
elderly compared to the younger patients with TBI. It has been also reported that the
duration of hospital stay is significantly longer in the elderly than younger patients
with TBI [53]. The elderly patient frequently presents numerous comorbidities (dia-
betes mellitus, neurodegenerative diseases, arterial hypertension, chronic vascular
encephalopathy) at the time of trauma, which can mask the clinical picture, postpone
treatment, and influence prognosis: as an example, age-related atrophy may provide
space for an intracranial hemorrhage to expand substantially before leading to clini-
cally apparent signs or symptoms that would be detected by the GCS [54].
Morphologically, the distribution of traumatic intracranial lesion varies in the age
groups. Diffuse axonal injury (DAI) is less common in the elderly than the young. In
contrast, focal injury is more common in the elderly. It is well known that the subdu-
ral, contusional, and intracerebral hematomas are more common lesions in the elderly
than the young, although epidural hematomas are less common in the elderly. Those
54 G. M. Di Lella et al.

a b e

c d

Fig. 3.11 SAH, epidural hematoma, and multiple brain contusions in polytrauma. Axial CT scans
in a 69-year-old patient with severe closed head trauma show the classic biconvex configuration of
an acute epidural hematoma in the left parietal region (a) and right frontal and left parietal hemor-
rhagic contusions (the right frontal lesions due to contrecoup mechanism) (b–d) with mild sur-
rounding edema. Traumatic subarachnoid hemorrhage and tiny subdural right hematoma are also
present. Bone CT reconstruction shows a nondisplaced skull fracture of the left parieto-temporal
bone underlying the epidural hematoma (e). Note the subgaleal acute, hyperdense hematoma in the
left temporal area (a)

characteristics of intracranial lesion have been explained by morphological changes

related to aging. The elderly patients show a markedly different survival trend in com-
parison with other age groups. Death within 48 hours of admission is not different
among all age groups. After that, only the elderly group shows a progressive decrease
in survival until the rate leveled off at approximately 35%, whereas the other age
groups tend to level off at approximately 60–80% survival. The “talk and deteriorate
(T&D)” concept is defined as a patient who present a relatively good neurological
condition in the early phase after TBI and then deteriorate to a severe neurological
status within 48 hours. It is much more common in the elderly and is often induced by
the delay of posttraumatic changes such as hyperemia/hyperperfusion, traumatic
intracerebral hematoma, expansion of subdural hematoma, or aggravation of trau-
matic contusional edema. The T&D is much more common in old patients after TBI
with resulting cerebral contusion. Cerebral contusional edema has been classified as
early massive edema and delayed-pericontusional edema. The early massive edema is
defined as a hypo intensity core on diffusion-weighted magnetic resonance image
(MRI), which appears within 24 h after TBI, suggesting that intra- and extracellular
components undergo disintegration and homogenization in the central area of the con-
tusion. In contrast, delayed-pericontusional edema is defined as predominant cellular
swelling in the peripheral area. There is a crescent-shaped border zone of very high
3 Neurovascular Emergencies in Geriatric Patients 55

ADC value on MRI between central and peripheral area. In spite of CBF reduction,
fluid amount is excessive in the area of the cerebral contusion. In addition, hyperemia/
hyperperfusion subsequent to ischemia enhances the increase of post contusional
edema, resulting in delayed deterioration. Delayed traumatic intracerebral hematoma
and expansion of either traumatic acute subdural hematoma or intracerebral hema-
toma may be other important clinical entities for delayed deterioration. A peculiar
entity of delayed deterioration after TBI, the delayed posttraumatic acute subdural
hematoma (DASH), has been reported in elderly patients. DASH has been defined as
an acute subdural hematoma that is not apparent on the initial computed tomography
(CT), and suddenly arise on a follow-up CT after 9–72 h after TBI. Thus, DASH
should be suspected in elderly, anticoagulated, mild TBI patients, including those who
present in the ER with GCS scores of 15 and normal initial CT [55–57]. Current
guidelines recommend “In case of head trauma, the head CT scan is the first line
examination and is recommended for any patient without loss of consciousness or
post-traumatic amnesia, if any of the following is present: neurological deficit, vomit-
ing, severe headache, age over 65 years, suspected skull-base fracture, Glasgow score
<15, coagulopathy, trauma with dangerous mechanism” [58, 59]. A fundamental role
in the approach of the traumatic patient is represented by neuroimaging and in particu-
lar by CT, which through a prompt diagnosis in acute, indicates the management and
helps predict patient outcomes of all ages spectrum. A fundamental role in the
approach to the traumatic patient is represented by neuroimaging and in particular by
CT, which through a timely diagnosis in acute indicates management and helps pre-
dict the outcomes of patients of all age groups. In particular, CT must promptly recog-
nize pathological conditions that require urgent surgery (extensive expansive lesions)
and/or intracranial hypertension. In this context and especially when fractures of the
skull base are present, the integration of a dynamic CT angio study may be useful, for
the evaluation of the main vascular structures in order to exclude arterial dissections,
aneurysms/pseudoaneurysms, and thrombosis of the venous sinuses and of the cere-
bral veins. The unstable clinical conditions of the traumatic patient, the reduced avail-
ability on the territory and the duration of the examination, relegate the MR in urgency
to a secondary role. The damage incurred by TBI can be differentiated into primary
and secondary mechanisms. Post traumatic head lesions included both primary inju-
ries, that are typically defined as the direct mechanical damage caused by trauma
hemorrhagic parenchymal contusions, brain stem injury, traumatic axonal injury
(TAI), parenchymal hematomas, subdural, subarachnoid or extra-dural hematoma,
cranial vault fractures, and secondary injury mechanisms, that are varied and related
to disruption of the blood brain barrier, production of reactive oxygen species and
resultant oxidative stress, metabolic dysfunction, inflammation, and excitotoxicity.
They may become apparent as diffuse cerebral hyperemia, cytotoxic and/or vasogenic
edema, and tissue ischemia [60, 61].

3.4.1 Posttraumatic Subarachnoid Hemorrhage (t-ESA)

Posttraumatic subarachnoid hemorrhage is due to a tearing of the bridging veins or

pial vessels in contact with the sub-arachnoid space; if the choroid plexuses and/or
parenchymal foci contusive juxtaventricular foci are involved, the hemoventricle
56 G. M. Di Lella et al.

can also be found. t-ESA is more focal and circumscribed than nontraumatic ESA
and is frequently localized in the peri-sylvian regions and in the cerebral sulci adja-
cent to the and/or to epi/sub-dural blood collections [62] (Fig. 3.11).
The clinical presentation appears mostly in the form of headache, classically
defined as maximal at onset and “the worst of life.” The most common cause is
traumatic, also representing the most common form of intracranial hemorrhage in
trauma; approximately 80% of nontraumatic SAH are due to aneurysmal rupture,
with the remainder from idiopathic peri-mesencephalic hemorrhage or other less
common causes.
Noncontrast head CT is the primary means of diagnosis, with the advanced gen-
eration scanners approaching a 100% sensitivity, if completed within 6 h from
symptom onset. The bleeding in the subarachnoid space will result in hyper density
in the first hours on CT-scanner. Within the first 24 h, it is positive in 90/95% of
cases; it should be noted that spontaneous hyper density gradually disappears and
that after a week it is only found in 50% cases. In general, hyper density will depend
on hemoglobin level, amount of blood, and delays between performing the scan and
bleeding [63]. One pitfall might be that the blood and adjacent bone, which both
appear white, can be difficult to distinguish from each other, especially in small
bleeding and in the anemia (sensitivity decreases when the hematocrit is <30%); in
addition, motion artifacts in scans of restless patients can making such scans techni-
cally suboptimal and obscure the diagnosis [64]. In these cases, the Dual Source
scanners may show some edge in the demonstration of such collections.
On MRI the fluid attenuated inversion recovery (FLAIR)/gradient reversal echo
(GRE)/susceptibility weighted imaging (SWI) sequences have a good sensitivity for
the detection of acute SAH in the first 48 h and are complimentary to the CT scans
[65]; however, they are not suitable for a rapid assessment of head injuries. SAH can
be diagnosed by GRE/SWI sequences by its dark signal intensity (“blooming”),
surrounded by the CSF signal intensity. More specifically, the FLAIR sequences,
which are the most sensitive in the first days compared to T1, T2, T2*, show a
hypersignal in the basal cisterns and the sulci of the convexity [64, 66]. The radiolo-
gist evaluation must be careful, because there are other etiologies at the origin of a
hypersignal in FLAIR in the subarachnoid spaces, such as meningitis, hyperoxy-
genation, and metallic artefacts. After a few days from the onset T2* sequences
show hemosiderin deposits, i.e., in the cisterns of the base, or in the cortical furrows.
This modality does not require radiation, though several limitations exist, including
limited availability in the ED, the time required for scanning, the potential for
inducing claustrophobia, and the need for specialist interpretation. MRI/MRA is
optimal for patients who present in a subacute or chronic timeframe [67].

3.4.2 Cerebral Contusion (PTBCs)

Posttraumatic brain contusions (PTBCs) represent one of the most frequent lesions
in patients with moderate or severe traumatic brain injury (TBI). PTBCs are tradi-
tionally considered primary injuries, but they have an inherent capacity to increase
3 Neurovascular Emergencies in Geriatric Patients 57

in size, generate perilesional edema, and cause mass effect [68]. These lesions are
cortical and due to the impact with the bone surfaces (e.g., the petrous bone, sphe-
noid, cribriform plate, orbit roof) and the dura mater (more resistant and irregular).
There are therefore more common localizations, such as the fronto-basal regions
and the temporal and frontal poles; they typically occur at (“coup”) or in front
(“countercoup”) with respect to the site of the blunt trauma. Bruises frequently are
multifocal and bilateral, usually involving the superficial gray matter that often
bleed, particularly those found in “countercoup” areas. The use in the acute phase is
represented almost exclusively by NCCT; however, it can underestimate the number
and size of blunt foci; there are moreover less common localizations, as is in the
case of Duret hemorrhages, generally associated with other lesions (Fig. 3.12).
Therefore, MRI in a sub-acute/chronic structural phase improves prognostic
modeling after TBI by identifying evidence of neurotrauma that may not be detected
by head CT. They are recognized as hypo dense cortical-subcortical areas and in
some cases a contextual hyper dense component of hemorrhagic significance may
be highlighted.

a b c d

e f g h

Fig. 3.12 Duret brainstem hemorrhage in posttraumatic left subdural hematoma. A 75-year-old
woman with head trauma due to sudden loss of consciousness. A CT study in ER showed an acute
left hemispherical subdural hematoma compressing the hemisphere and lateral ventricle, with
uncal hernia and incarceration of the temporal horn of the lateral ventricle; note left-to-right mid-
line shift (a, b). There is also the evidence of midbrain Duret hemorrhage (usually due to stretch-
ing/tearing of pontine perforators, c). Follow-up non-contrast CT scan after the removal of the
hematoma shows re-expansion of the left ventricular hemisystem (e, f); MRI with FLAIR (d) and
T1 TSE (g) sequences confirm the reduction of the subdural hemorrhage and of the associated
mass effect. CT follow-up after 60 days demonstrates an “ex vacuo” dilation of the horn and trine
of the left lateral ventricle (h)
58 G. M. Di Lella et al.

In patients with severe cerebral contusions, early massive edema occurs within
the period of 24–72 h post-trauma. This type of edema results in progressive eleva-
tion of intracranial pressure (ICP) and clinical deterioration giving rise to a clinical
course termed “talk-and-deteriorate” [69]. DWI measures the freedom of molecular
motion of water in tissue and is useful in identifying pathologic lesions including
foci of axonal injury and infarction. DWI is best used in conjunction with its associ-
ated ADC map, which can distinguish between cytotoxic and vasogenic edema in
the acute and subacute phases and is highly sensitive in the detection of secondary
acute ischemic infarction associated with TBI.
Despite intensive medical therapy, the elevated ICP in patients with early mas-
sive edema is often uncontrollable and fatal.

3.4.3 Post-traumatic Intracerebral Hematomas (t-ICH)

t-ICH results from injury to intraparenchymal arteries or veins secondary to rota-

tional strain or penetrating trauma and are usually located in the frontal-temporal
white matter or basal ganglia; ICHs collect between relatively intact parenchyma,
in contrast to hemorrhagic contusions where the hemorrhage is within a larger
area of injured edematous brain. Prognosis of isolated ICH is generally good, but
worsens when the lesion coexists with marked mass effect, traumatic axonal
injury (TAI), or multiple basal ganglia hemorrhages. When CTA is also per-
formed, the “spot sign,” or active extravasation of contrast into the hematoma,
predicts future expansion of the hematoma and worsens clinical outcome [61, 70]
(Fig. 3.13).

3.4.4 Traumatic Axonal Injury (TAI)

Traumatic axonal injury is a condition defined as multiple, scattered, small hemor-

rhagic, and/or nonhemorrhagic lesions, alongside brain swelling, in a more confined
white matter distribution on imaging studies, together with impaired axoplasmic
transport, axonal swelling, and disconnection after traumatic brain injury [71]. TAI
is thought to be caused by a variety of traumatic mechanisms involving fast accel-
eration and/or deceleration, including motor vehicle accidents, falls from height,
and blunt assault [72]; the distribution of traumatic lesions has a predisposition for
white matter tracts in the midline of the brain, including the corpus callosum, inter-
nal capsule, cerebral peduncles, brainstem, and the gray–white junction of the cere-
bral cortex (Figs. 3.14 and 3.15). CT is capable of identifying large TAI-related
hemorrhage, but nonhemorrhagic lesions and small TAI hemorrhage are virtually
impossible to identify using CT and therefore can be easily lost [73]. Conventional
MRI (cMRI) has a higher sensitivity in demonstrating lesions in the brainstem and
the deep white matter, making it more sensitive for identifying axonal injury
3 Neurovascular Emergencies in Geriatric Patients 59

a b c d

e f g h

Fig. 3.13 Hemorrhagic brain contusions in head trauma. A 73-year-old patient with head trauma
in ASA therapy. Non-contrast CT study in ER demonstrated an ample atypical intra-axial left
frontal hemorrhage with initial surrounding edema and mass effect (a). The next day a CT angio-
graphic exam showed stability of the collection, with no signs of underlying vascular malforma-
tions (b). The subsequent MR study confirmed the diagnosis. T1-w (d) evidentiates the initial
peripheral methemoglobin ring surrounding the oxy-deoxyhemoglobin content of the fresh lesion,
while the SWI (c) sequence shows a little subarachnoid spread and absence of previous hemor-
rhages. After another light head trauma 3 month later, axial CT showed another intra-axial hema-
toma in the right posterior parietal lobe with surrounding edema (e). The subsequent MR study
with TOF sequence confirmed the diagnosis, excluding also in this case signs of vascular malfor-
mations and showing the remnants of the previous frontal hemorrhage (f–h)

compared to CT [74]. The MRI gradient echo sequence (GRE) is able to detect
heme and heme breakdown products, making it a suitable method for discovering
small hemorrhagic lesions. Susceptibility-weighted imaging (SWI) as a variant
sequence of GRE imaging should be considered the “gold standard” for identifying
TAI lesions. It has a higher sensitivity for hemorrhage than GRE, which makes it
more useful for early diagnosis of TAI. Diffusion-weighted imaging (DWI) can
accurately examine nonhemorrhagic lesions. High signal DWI can be used in
patients with early stage TAI. Lesions found represent cellular swelling and cyto-
toxic edema. DWI may aid in predicting clinical outcome after TAI. DWI is more
capable of determining the severity of the injury and estimating the long-term prog-
nosis than MRI techniques [71, 75, 76].
Diffusion tensor imaging (DTI) is an improved form of DWI. It can be used to
evaluate nerve alignment, white matter microstructure, and the morphology around
nerve fibers. Within the first 24 h after trauma, DTI can detect white matter regions
with reduced anisotropy, making it an adequate technique for detecting TAI. CT
scanning is more widely used in the acute phase, due to its much shorter scanning
60 G. M. Di Lella et al.

a b

c d

Fig. 3.14 Bilateral frontal cerebral contusions and TAI of a 65-year-old male (a–d). Non-contrast
CT in ER after close head trauma due to a car accident. The images show bilateral cortical-­
subcortical inhomogeneous hypodense parenchymal areas, partially due to vasogenic edema,
directly related with the impact. Also note the multiple small hyperdense foci, more evident in (b),
which represent associated manifestations of traumatic axonal injures (TAI), secondary to the axo-
nal traumatic strain, related to the tissue deformation caused by the differential kinetic energy with
the skull

time. MRI scanning should be performed as soon as the condition of the patient
allows it, so the full extent of trauma can be mapped and white matter volume pro-
spectively followed-up [73, 77].
Acute treatment in the elderly with moderate to severe head injury involves an
acute neurosurgical approach including intracranial pressure monitoring (ICP), cra-
niotomy, and decompression craniotomy; tSAH may impair the absorption of CSF
and may produce hydrocephalus. Posttraumatic vasospasm (PTV) is a significant
3 Neurovascular Emergencies in Geriatric Patients 61

a b c

d e f

Fig. 3.15 Traumatic axonal injury (TAI). Non-contrast CT study in a 67-year-old man involved in
a high-energy head trauma shows tiny hemorrhagic foci in the subcortical white matter (c) and in
the left internal capsule (a). Blood is also present in the right lateral ventricle (b). These micro-
bleeds are typical imaging markers of diffuse axonal injury (DAI). FLAIR images well depict the
edema surrounding the tiny hemorrhagic foci in the left internal capsule (d), while the SWI (e, f)
sequence shows other hemorrhagic foci in the subcortical white matter and in the right lateral
ventricle. Note how the MRI study more accurately demonstrates the presence and the extension
of diffuse axonal damage manifestations

secondary insult to the injured brain. It typically develops between 12 h and 5 days
after the injury and lasts between 12 h and 30 days.
However, preexisting clinical conditions dramatically influence the prognosis in
elderly patients; therefore, invasive surgical treatment in this population remains
controversial.

3.5 Extra-axial Hemorrhages

3.5.1 Epidural Hematoma

Epidural hematoma (EDH) represents an extremely rare event in the elderly pop-
ulation: an overwhelming majority of cases arise in fact after a high energy
62 G. M. Di Lella et al.

traumatic brain injury (TBI), with associated skull fracture that involves an
artery, often represented by the middle meningeal artery (MMA). Such events
are typical of the young male population. Other causes, more frequent in the
elderly due to underlying comorbidity, are coagulopathy, secondary effect of
thrombolysis, vascular malformation, neoplasm, epidural anesthesia, or Paget
disease of skull. On the other hand, spontaneous EDHs are rare, and generally
arise from a skull primary or secondary tumor. EDHs, generally unilateral and
supratentorial, derive from an arterial bleeding in 90% of cases and therefore
show a rapid expansion, reaching the maximum size after 36 h. EDHs have the
typical shape of a biconvex lens, often also if of venous origin, are extra-axial
and determine rapid compression and displacement of the underlying brain
parenchyma with huge mass effect: thus a quick diagnosis followed by immedi-
ate surgical approach have paramount importance, in order to avoid a poor out-
come, or the death of the patients due to the brain damage. EDH of suspected
venous origin, with thickness not superior to 1 cm, could be observed with sub-
sequent TC scan in the following 36 h. Although typical in shape, imaging fea-
tures and clinical history, EDHs may pose DD with SDHs, that in some cases
may have biconvex shape: in this case it is useful to remember that EDHs, differ-
ently from SDHs, do not cross the cranial sutures. Other, less frequent DDs are
with extra-axial tumors, like meningiomas or soft component of skull or dural
primary (lymphomas, primary sarcomas) or secondary lesions. Also some infec-
tious/inflammatory event may pose a DD with EDH, epidural empyema from
skull osteomyelitis or granulomatous tubercular osseous localizations. The
NCCT exam is usually diagnostic: a second level study is not necessary and not
recommended, in order to avoid a delay of the surgical treatment, which could in
order cause a significant worsening of the outcome. EDHs appear as a thick
biconvex homogeneously hyper dense collection located under the area of the
skull trauma where, in the case of arterial origin, a fracture responsible for the
torn of an arterial vessel is almost inevitably visible (Fig. 3.16). The density may
also be low or inhomogeneous, due to the contemporary presence of uncoagu-
lated blood: in this case the collection is in the hyperacute phase. The eventual
presence of air (20%) is related to the fracture of a paranasal sinus or mastoid
proximal to the collection. A small, iso or hypodense collection is almost always
of venous origin. MRI is useful in case of nontraumatic collections. In the acute
phase, the content is hypointense in T1 and variable, hypo to hyperintense on
T2wi: in the subacute/chronic phase the T1 signal becomes hyperintense, while
in T2 it appears hypointense in the subacute period and hyperintense in the
chronic phase. The post contrast T1wi may be useful in case of venous collection
in order to demonstrate displacement and patency of dural sinuses.

3.5.2 Subdural Hematoma (SDH)

Subdural hematomas (SDH) surely represent a sizeable cause of cerebrovascular

emergencies in the elderly. The incidence of falls, considered to be the leading cause

AL GRAWANY
3 Neurovascular Emergencies in Geriatric Patients 63

a b c

d e f

Fig. 3.16 Epidural hematoma. Non-contrast CT study in a 71-year-old woman with head trauma
shows the classic biconvex appearance of an acute left epidural hematoma, associated with mass
effect, compression of the left hemisphere and lateral ventricle, left-to-right subfalcine herniation
and resulting ample midline shift (a–c). Note the hematoma of adjacent soft tissues (a). Axial CT
study after surgical evacuation shows the disappearance of the epidural blood collection and con-
sequently of the mass effect, with the presence of bilateral frontal pneumocephalus (d). MRI
FLAIR axial image, several days after surgery, showing the presence of tiny bilateral subdural
hematomas and a left subgaleal collection over the craniotomy (e). Bone CT 3D-reconstruction
shows a non-displaced skull fracture of the temporal and parietal bone underlying the hematoma (f)

of SDH [78–80], has increased worldwide along with the augmented percentage of
elderly in the population. Sixty percent of patients are hospitalized due to injuries
sustained in a fall, according to the National Trauma Data Bank in the United States,
55,729 (61%) had sustained injuries from falling [81]. In older patients, reduced
brain parenchyma has been associated with an increased risk of SDH, which may
even occur following minor trauma [82]. SDH usually results from tears in bridging
veins, which cross between the cerebral cortex and the dural sinus [83], or, less
frequently, a rupture of the superior cortical arteries [84]. Blood accumulates in the
space surrounding the brain parenchyma, between the arachnoid mater and the dura
[85]. Increased intracranial pressure caused by a hematoma causes further compres-
sion and damage to the brain tissue (Fig. 3.17). Moreover as the patients grow older,
there is a higher prevalence of comorbidities and increased use of medications,
including anticoagulants and polypharmacy. This can heighten the risk of bleeding
and developing further complications. Fortunately overtime there has been a
decrease in the mortality rate: in the 1990s, the mortality rate for acute SDH was
reported to be as high as 60% [79]. The mortality rate of SDH decreased to a level
of 20% around the year 2000 and has fallen as low as 14% within the last decade
64 G. M. Di Lella et al.

a b

c d

Fig. 3.17 Subdural hematoma. NCCT study in ER of a 81-year-old man with consciousness
reduction and confusion showing right hemispherical subacute subdural hematoma, with signs of
recent rebleeding, that compresses the right hemisphere and lateral ventricle, with right-to-left
subfalcine herniation, resulting in midline shift (a, b). Immediate postsurgical NCCT shows the
thickness reduction of the subdural hematoma (with presence of an air-fluid level) and the associ-
ated reduced compression on the right hemisphere and lateral ventricle (c, d)

[79]. However, acute SDH has been reported to be a poor prognostic factor for those
patients with a traumatic brain injury [86], particularly in elder patients. There was
in fact higher mortality for the elderly following falls compared to young adult
patients, after adjusting for preexisting comorbidities and severity of injury [78].
3 Neurovascular Emergencies in Geriatric Patients 65

Being an almost typical acute neurological event, the patient is generally evaluated
with a noncontrast TC study (NCTC). The recent multislice CT systems generally
available in the radiological departments being nowadays capable to acquire 64 or
more (128, 256, 320 up to 512 sub-mm slices) simultaneously, make generally pos-
sible a good quality study even in an uncooperative patient. An SDH, regardless its
phase, appears as a crescentic extra-axial collection of variable breadth and longitu-
dinal extension along the surface of the affected hemisphere. Less frequently
(15–20%), the SDH can involve both the hemispheres (Fig. 3.18), or be located in
the posterior fossa. In the hyperacute phase (less than 6 h), the subdural collection
appear hypodense or at least heterogeneous, due to the presence of mostly uncoagu-
lated blood. In the acute phase, it appears homogeneously hyperdense in 60% of
cases, while in 40% is mixed hyper-, hypodense with active bleeding (“swirl” sign),
torn arachnoid with CSF accumulation, clot retraction. Rarely the collection is
isodense, due to coagulopathy, anemia (Hgb <8–10 g/dL) ·If no new hemorrhage,
density gradually decreases to become isodense to brain parenchyma in the

a b c

d e f

Fig. 3.18 Bilateral subdural hematomas. NCCT study in ER of a 81-year-old woman with severe
headache, showing bilateral hemispherical subacute subdural hematoma (right>left): in the right,
more sample collection, there are signs of recent rebleeding, represented by the irregular areas of
hyperdensity (a). Note the bilateral compression of the cerebral hemispheres and lateral ventricles,
with right-to-left subfalcine herniation, resulting in midline shift (a–c). Follow-up CT days after
surgery showed the reduction of both the subdural hematomas and of the compression on the
hemispheres and the lateral ventricles. (f) The coronal plane shows the reduction of the right-to-left
subfalcine herniation (d–f)
66 G. M. Di Lella et al.

subacute phase. Post contrast CT is generally unnecessary in this phase, while in the
subacute period it could come in handy, because in certain case a thin SDH could be
indistinguishable from the adjacent brain cortex.
On MRI a SDH generally often follow the fashion of intraparenchymal hemor-
rhage. On TlWI in the hyper acute phase (less than 12 h) appear iso to mildly hyper
intense. In the acute (12 h to 2 days) is mildly hypo intense. On T2WI hyper acute
is mildly hyper intense. In the acute appear hypo intense. On the FLAIR sequence,
it is typically hyper intense to CSF. Signal intensity varies depending on relative Tl
and T2 effects. Acute hematomas can be isointense to CSF due to T2 shortening
effects of intracellular methemoglobin. FLAIR is often the most reliable sequence.
On T2* GRE the collection is hypo intense unless hyper acute. Finally on DWl it
shows heterogeneous signal (nonspecific), but this sequence may be useful in order
to differentiate extra axial empyema (marked central hyper intensity) from hemor-
rhage. Among the differential diagnoses it is possible to consider other subdural
collection, like hygroma, that shows clear CSF without encapsulating membranes,
subdural effusion, made by xanthochromic fluid secondary to extravasation of
plasma from membrane, that appears 1–3 days post-trauma; near CSF density/
intensity, and empyema, that generally has peripheral enhancement and shows
hyper intensity on FLAIR and restricted diffusion on DWl. The epidural hematoma
is a biconvex extra-axial collection, associated with fracture. It may cross dural
attachments, limited by sutures Pachymeningopathies (thickened dura) derives from
chronic meningitis (may be indistinguishable), neurosarcoid, with nodular, “lumpy-­
bumpy” appearance, or postsurgical (e.g., shunt), caused by intracranial hypoten-
sion with “slumping” midbrain and tonsillar herniation. Tumors, like meningiomas,
lymphomas, leukemia, metastases are generally dural-based, enhancing masses,
which in some cases may involve the adjacent skull and extracranial soft tissue. In
the peripheral brain infarction, the cortex is involved, not displaced, and is typically
hyper intense on DWl.
Subacute and chronic SDH (sSDH and cSDH) are infrequently the cause of a
neurovascular emergence, due to the subtle onset and slow progression of the
symptoms, also if in some cases is possible to withstand a patient with sudden loss
of consciousness. Nevertheless the sSDH may represent a diagnostic challenge,
especially with a NCCT study; as stated above a thin crescentic collection, with-
out signs of recent rebleeding or older, chronic component, could be difficult to
diagnose from a nonexperienced radiologist. In this case the diagnosis is made
easier by administration of iodinated contrast media, eventually for other mor-
bidities, while a conventional MRI study with a FLAIR sequence never misses the
collection, albeit making sometimes necessary the differential diagnosis (DD)
with other pathologies.
The diagnosis is much more easy in case of chronic SDH, which appears clearly
hypodense on NCCT. In these case, without signs of rebleeding or presence of
membranes inside the collection, it is necessary in some cases to distinguish a cSDH
3 Neurovascular Emergencies in Geriatric Patients 67

from a hygroma: the DD could be made measuring the density of the collection
compared with that of the CSF in the ventricles. The density of a cSDH is gener-
ally higher.

3.6 Cerebral Venous Thrombosis

Cerebral venous thrombosis (CVT) is an overall not frequent cerebrovascular

pathology (incidence of CVT is estimated nowadays to be 1.32/100,000/year in
Western Europe), accounting for 1% of strokes [87], and represents a really rare
disease in the adult and elderly population: the vast majority of cases being observed
in the young female population after a pregnancy or during oral contraceptives ther-
apy. Nevertheless other causes like trauma, infection, inflammation or metabolic
(dehydration, cirrhosis, thyrotoxicosis), and hematological (coagulopathy) are more
common in the latest decades of life. Albeit rare CVT is potentially deadly (10–20%
of untreated cases), and while the symptoms are often nonspecific, it is necessary to
keep this pathology in the range of the possible diagnosis, also given the possibility
of accurate diagnosis offered by the venous intracranial system analysis of a CTA or
an MRI PC and post-contrast 3D sequence [88]. Unfortunately a patient with VCT
may describe subtle symptoms, often represented only by headache, nausea, vomit-
ing, without neurological deficit. The NCCT may be negative or nonspecific: in the
latter case, it is possible to find smooth areas of white and gray matter edema, some-
times multiple and often without a definite vascular “arterial” pattern, as in the case
of superior sagittal sinus involvement, with eventual signs of concurrent hemor-
rhage, representing the effect of venous congestion. In the more typical cases, the
NCCT may show slight hyperdensity of involved sinuses (triangle sign on SSS)
while the post-contrast scan reveals the hypodensity of the blood clot [89]. The
parenchymal involvement is related generally to the occluded vessel: the temporal
lobe is frequently affected in transverse and sigmoid sinus or Labbe’ CVT, while
thalami and basal ganglia are related, often bilaterally, in case of CVT located in the
deep system (Internal cerebral vein, Vein of Galen, Straight sinus). In some cases
instead the thrombosis could be limited to a small vein of the deep system and the
subsequent surrounding edema may mimic an expansive lesion, while in others
multiple venous vessels in different cerebral areas may be involved. In 30–40% of
cases CVT presents or evolves with hemorrhage, generally intraparenchimal, focal,
or petechial (Fig. 3.19). Sometimes a concurrent SAH may be seen. The hemor-
rhage worsens the prognosis and the outcome in patients with VCT. In fact it makes
much more challenging the primary treatment, which relies on the administration of
anticoagulative (not antithrombotic) drugs, whose effect could worsen the size and
therefore the effect of hemorrhage. This occurrence makes of paramount impor-
tance the need for an early diagnosis of VCT, before the onset of the subsequent
bleeding.
68 G. M. Di Lella et al.

a b c

d e f

Fig. 3.19 Dural sinus thrombosis. A 74-year-old man hospitalized in a COVID+ intensive care
unit for sudden and prolonged loss of consciousness. CT axial and ACT study showed an inhomo-
geneous hemorrhage with initial surrounding vasogenic edema in the left temporal lobe; the angio-
­CT demonstrated thrombosis of left transverse and sigmoid sinuses, with involvement of the
homolateral Labbè vein and intracranial tract of the jugular vein (a–c). Follow-up MRI with 3D
TOF angio-sequences confirmed the involvement of the venous structures, with extension to the
extracranial proximal left jugular vein. Also note the enlargement of the vasogenic edema sur-
rounding the hemorrhage (d–f)

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AL GRAWANY
Head and Neck in Geriatric Patients
4
T. Popolizio, L. Cassano, A. Pennelli, R. Izzo, G. Fascia,
M. Masciavè, and Giuseppe Guglielmi

Learning Objectives
After reading this chapter, readers should be able to:

• Detect the more frequent diseases in geriatric patients

• Be aware the radiologic characteristics
• Know the clinical manifestations of the main geriatric diseases of the head of
the neck

4.1 Ear

4.1.1 Chronic Suppurative Otitis Media

Chronic suppurative otitis media is a very common disease that should be carefully
treated, as severe complications can develop. Despite the significantly decreased
incidence of chronic suppurative otitis media related complications since the

T. Popolizio · A. Pennelli · R. Izzo

Radiology Unit, Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
L. Cassano
Otolaryngology Unit, Hospital “Casa Sollievo Della Sofferenza”,
San Giovanni Rotondo, Italy
e-mail: [email protected]
G. Fascia · M. Masciavè
Department of Clinical and Experimental Medicine, Foggia University School of Medicine,
Foggia, Italy
e-mail: [email protected]
G. Guglielmi (*)
Clinical and Experimental Medicine, University of Foggia, Foggia, Foggia, Italy
e-mail: [email protected], http://www.unifg.it

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 73

G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_4
74 T. Popolizio et al.

introduction of antibiotics, this clinical problem has not been eliminated. Chronic
suppurative otitis media remains a serious concern, particularly in developing coun-
tries and socioeconomically poor regions [1–4].
Complications of CSOM can be classed as extracranial (EC) or intracranial (IC).
Extracranial complications include mastoid abscess, petrositis, labyrinthitis, facial
nerve paralysis (FNP), and Bezold’s abscess. Intracranial complications comprise
intracranial abscess (including extradural, epidural, subdural, perisigmoid sinus,
and brain abscesses), lateral sinus thrombophlebitis (LST), meningitis, and otitic
hydrocephalus. The pathophysiology of complications of CSOM remains some-
what of a mystery. The pathways of EC and IC complications include thrombophle-
bitis of the venules of the adjoining cranial bones, bone erosion by pressure or
enzymatic actions, preformed pathways, and hematogenous spread [5–8].

4.1.1.1 Extracranial Complication

Coalescent Mastoiditis
The treatment for acute mastoiditis can fail and sometimes there is an enzymatic
destruction of the mastoid septa and the development of an intramastoid empyema.
TC can visualize these erosive changes very early [9, 10].

Subperiosteal Abscess
It typically occurs via direct extension of the inflammatory debris through a defect
in the external context of the mastoid sinus. This passage can occur in any direction:
post-auricular, common as the bone is particularly thin (Macewan’s triangle) or
infero-medial, medial to the attachment of sternocleidomastoid (resulting in a
Bezold’s abscess) [11].
Bezold’s abscess is comparable to the subperiosteal abscess but takes place
through a bony defect at the mastoid tip, medial to the insertion of the posterior
belly of digastric.
CT can demonstrate coalescent mastoiditis with erosion of the medial mastoid
tip [12].
This defect could let infection expand into the neck.
CT also shows thickening of the omolateral sternocleidomastoid muscles with
surrounding inflammatory changes, heterogeneous post contrast enhancement with
rim enhancing cystic lesion [13, 14].

Petrositis
It is an infection with involvement of bone at petrous apex of the temporal bone.
CT is the modality of choice to evaluate bony changes in the temporal bone,
revealing debris within the petrous apex, air cells, and erosive lysis of bony septa
[15–18].
Disruption of the anterior or posterior bony cortex may occur resulting in fulmi-
nant intracranial complication (meningitis, empyema, dural sinus thrombosis, cra-
nial neuropathy).
4 Head and Neck in Geriatric Patients 75

At the onset diagnosis of petrus, apex inflammatory disease is best made with
high-resolution CT. Later MR imaging becomes important to assess intracranial
complications [19, 20].

Labyrinthitis
The acute stage results when bacteria and other pathogenic noxae filled the perilym-
phatic spaces, inducing acute inflammatory response.
The CT is normal at this stage, and the endolymphatic space is spared.
The majority of patients will not have enhancement or any imaging findings.
Sometimes there is enhancement of the normally not enhanced fluid-filled spaces of
the labyrinth on T1-weighted images [21, 22].
The enhancement may persist long after symptoms, there is an accumulation of
gadolinium within inflamed labyrinthine membrane because of the breakdown of
the labyrinthine vasculature [10].
The combination of pathological labyrinthine enhancement and thickening/
enhancement of the seventh nerve should induce suspicion of EAC [23, 24].
If acute labyrinthitis does not resolve, the progression to chronic disease results
first in fibrous change and then in ossification.
The fibrous stage is characterized by fibroblastic proliferation within the peri-
lymphatic spaces (begins after 2 weeks after the onset of infection). CT is normal
while T2-weighed MR images show replacement of the normal high signal of the
fluid-filled spaces of the labyrinth, detected at the cochlear apex [25, 26].
The ossify stage consists of pathological ossification of the membranous laby-
rinth [27, 28].
The CT appearance is characterized by high-density bone deposition within the
membranous labyrinth, from hazy increase in density within fluid spaces of the
membranous labyrinth (mild disease) or focal areas of bony invasion on fluid spaces
(moderate disease) or with total obliteration by bony replacing fluid spaces (severe
disease) [29, 30].
MRI will show loss of normal signal fluid in membranous labyrinth in
T2-weighted images as hypointense foci in labyrinth.

Facial Nerve Involvement

It may occur facilitated by the development of dehiscence that allows the passage of
inflammatory products. CT and MRI are helpful for identifying bony facial canal
and soft tissue abnormalities, respectively. When using CT to evaluate the facial
nerve, pathology often can only be deducted by visualization of erosion or destruc-
tion of the adjacent bony facial nerve canal [31]. MRI, instead, visualizes soft tis-
sues well and so is more appropriate for evaluating soft tissue facial nerve
abnormalities. In high-resolution T2-weighted images or CISS images, the normal
facial nerve appears as a hypointense linear structure extending from the brainstem
to the IAC, anterior to the vestibulocochlear nerve, surrounded by T2 hyperintense
cerebrospinal fluid. The labyrinthine, tympanic, and mastoid segments of the facial
nerve are not typically well visualized in non-contrast images. Mastoiditis and acute
otitis media occur simultaneously determining engorgement of the normal aeration
76 T. Popolizio et al.

of the mastoid cells and reducing the vascular perfusion of the mucosa and decreases
the tissue penetration of antibiotics [32]. The inflammatory process on the facial
nerve canal, through canal dehiscence or invasion of infectious microorganisms,
results in inflammation and edema of the nerve inside its canal. The venous return
decreases and the pressure increases on the nerve, which leads to nerve dysfunction.
As the limits of the facial nerve canal are narrow, the accumulation of purulent
secretion inside the canal leads to mechanical compression and ischemic neuritis.
Persistent inflammation of the middle ear can also cause dehiscence of the facial
nerve canal, which leads to consequent facial paralysis [33].

Gradenigo’s Syndrome
It consists of the triad: suppurative otitis media, abducent nerve palsy, retroorbital
pain due to the extension of inflammation into Meckel cave. In patients with sup-
purative otis media infection may spread to the petrous apex of the temporal bone
and may be via pneumatized air cell tracts, through vascular channels or as a result
of direct extension through fascial planes. Abducent nerve is close to the petrous
apex separated from it only by dura mater, lies medial and adjacent to the trigeminal
ganglion, passing through Dorello canal. Extradural inflammation secondary to api-
cal petrositis may affect the above structures and generate the symptoms of
Gradenigo’s syndrome [34–40].

4.1.1.2 Intracranial Complications

Intracranial complications secondary to chronic otitis media (COM) include extra-
dural abscess, subdural abscess, meningitis (with or without encephalitis), otogenic
brain abscess, and lateral or sigmoid sinus thrombosis. Age (first decade or elderly),
immunosuppression, and presence of cholesteatoma are among the common influ-
encing factors for the development of intracranial complications [41].

Otogenic Brain Abscess

Otogenic brain abscesses are one of the most significant life-threatening complica-
tions of otologic infections. Given their low prevalence, otogenic brain abscesses
require a high index of suspicion for diagnosis [42, 43].
CT shows a soft tissue mass in the middle ear and mastoid with erosion of the
middle ear ossicles, expansion of the aditus of antrum, and erosion of the tegmen [44].
A well-demarcated oval mass with hypo-intense content and faint hyperintense
rim, with considerable mass effect on the brainstem. On FLAIR it has mixed con-
tent, thin hypointense rim, surrounding edema and mass-effect, hyperintense signal
in petrous bone. Following administration of contrast, there is rim enhancement of
the lesion and continuity with adjacent dural enhancement. The content demon-
strates intense diffusion restriction in DWI [45].

Sinus Thrombophlebitis
Sinus thrombophlebitis is caused by spread of infection to the inner wall of the
venous sinus, leading to the formation of a thrombus through the action of fibrin and
platelets, a process called endophlebitis [46].
4 Head and Neck in Geriatric Patients 77

CT scan is useful in demonstrating the classic “delta sign” of perisinus dural

enhancement and filling defect of the lateral sinus and also can avoid by excluding
other intracranial complications.
MRI is more sensitive than CT in detecting the thrombus. It shows blood flow,
sinus obstruction, and subsequent reversal of flow.
MRI can show increased signal intensity of the thrombus and detect LST not
identified on a routine CT. On T1-weighted MRI after contrast, thrombus appears as
soft tissue signal associated with vascular bright appearance of the dural wall: the
“delta” sign. MR venography, additionally, can demonstrate the loss of signal and
the absence of flow in the sinus. MRI is the investigation of choice and should be
performed in conjunction with CT, thereby fully evaluating associated otologic and
cerebral pathology. Magnetic resonance imaging is also useful for excluding an
adjacent subdural empyema, cerebritis, or cerebral abscess. Complete occlusion of
the sinus may occur, and presence of organisms may promote the formation of an
intrasinus abscess, whereby a septic emboli will have systemic manifestations in the
form of septicemia. Distal and proximal extensions may occur (Fig. 4.1) [47, 48].

a b

Fig. 4.1 Necrotizing external otitis. Meningo-encephalitis complication. Post-contrast T1-w cor-
onal (a) and axial (b): high contrast enhancement of right middle ear and mastoid with focal
thickening of the meningeal sheets in the middle crania fossa close to the petrous bone. In the late
sequences (b) a small area of vivid contrast enhancement with blurred borders can be appreciated
in the adjoining brain parenchyma. Findings are suggestive for meningo-encephalitis. NCCT coro-
nal MPR reconstruction (c): the right residual middle ear is filled with homogeneously hypodense
tissue. No erosions of the epitympanic recess are evident. The stapes shows some bone changes.
The tegmen tympani is eroded. The superior semicircular canal is not well depicted. On the left, a
small amount of homogeneous hypodense tissue is attached to the cochlear promontory
78 T. Popolizio et al.

4.1.2 Malignant Otitis Externa

Malignant (necrotizing) otitis externa (MOE) is an aggressive form of skin inflam-

mation of the external ear with a tendency to spread the infection to the temporal
cortical bone, leading to potential skull base osteomyelitis. The condition was first
reported by Toulmouche in 1838 [5] and is mentioned as the first case report of this
disease. The most common causative pathogen is Pseudomonas aeruginosa, espe-
cially in immunocompromised patients with diabetes, HIV, leukemia, granulocyto-
penia, anemia, on immunosuppressive therapy. In addition, some species of fungi
have been described as a causative agent, such as Aspergillus and Candida species.
Several cases of methicillin-resistant Staphylococcus aureus (MRSA) have been
described, and there is an ongoing increase in the MOE causative agents, such as
Klebsiella and Proteus mirabilis [26, 49].
The mechanism of tissue damage involves coagulation tissue necrosis because of
microangiopathy of small blood vessels. The most common clinical findings are
severe otalgia, otorrhea, impaired hearing, and granulation polyps. The facial nerve
is the most commonly involved cranial nerve, but glossopharyngeal, vagus, acces-
sory, or hypoglossal nerves could also be affected [50, 51].
Diagnosis was based on anamnesis, clinical examination, audiological assess-
ment, microbiological analysis of ear swab, and CT (computed tomography) scan of
the temporal bone, skull base, and endocranium. Notably, the diagnostic criteria
have changed over time [52, 53].
The primary treatment of MOE is long-term antimicrobial therapy. Other treat-
ment strategies include close follow-up of blood glucose levels and inflammation
markers and repeated local debridement of necrotic tissue. Lately, increased use of
the hyperbaric oxygen chamber has been noted as one of the therapeutic modalities.
CT and MRI are complementary in the evaluation of NEO [54, 55].
CT can better study cortical bone erosion in the region of external auditory canal,
especially at initial diagnosis, as small cortical erosions are better seen. On contrast-­
enhanced CT, there can be thickening and enhancing soft tissue and, in cases of
abscess, it can be observed cartilaginous bone ring enhancing collection with a cen-
ter of necrotic low attenuation [56].
MRI demonstrates soft tissue extension, cranial nerve involvement, parenchymal
and meningeal disease.
Subtemporal soft tissue abnormalities had low signal intensity on T1- and
T2-weighted images. Soft tissue changes improve but did not disappear completely
with treatment.
Either modality can be used to follow up soft tissue evolution. Nuclear imaging
studies are useful for continued surveillance of disease activity (Fig. 4.2).

4.1.3 Hearing Loss and Cognitive Decline

Alterations in sensory functions, vision, balance, and hearing are some of the most
common disturbances seen in the aging population and lead to dramatic social and
4 Head and Neck in Geriatric Patients 79

a b

Fig. 4.2 Necrotizing external otitis. Carotid stenosis complication. Axial (a) CT and coronal (b)
CT images show on the right side erosion of the glenoid joint, the jaw condyle, the apex of the
petrous part of the temporal bone, the carotid canal, and clivus. Hypodense tissue fills the middle
ear and mastoid cavities. There are no signs of bone or ossicular chain erosion. Post-contrast T1-w
MRI (c and d) shows avid enhancement of temporo-mandibular joint that extends to the petrous
part of the temporal bone, clivus pterygoid space, skull base, and cavernous sinus. Encasement of
the intrapetrous segments of the internal carotid artery can also be appreciated, which appear ste-
notic as depicted in the 3D MRI TOF (e). Also, the lesion expands through the masticatory space,
engaging the lateral pterygoid muscles, and the prevertebral space involving the posterior wall of
rhinopharynx, which is swelled. It focally overpasses the midline affecting the left lateral ptery-
goid muscle. Autologous 99mTc-HMPAO-labeled leukocyte scintigraphy (f) shows accumulation
in the right mastoid bone, skull base, rhinopharynx, and clivus
80 T. Popolizio et al.

Fig. 4.2 (continued)

functional disability. Among the senses affected by increasing age, hearing loss is
the most common. Presbycusis, or age-related hearing loss (ARHL), is a term that
refers to hearing loss as a result of physiologic and pathologic changes associated
with increasing age. As the aging population continues to grow, greater focus is
placed on understanding and attempting to reverse this sensory loss for the benefit
of geriatric patients. Today, there is an established although still evolving concept of
the workings of the outer ear, middle ear, and inner ear.
Presbycusis may present insidiously and be confounded by various medical, psy-
chological, and pharmacologic factors. Only after thorough history, examination,
and audiological testing can a diagnosis of presbycusis be made after excluding
concurrent medical and pharmacologic effects. In general, the first signs of ARHL
can be seen in late middle age with high-frequency hearing losses in the realm of
conversation frequencies, ultimately progressing subtly to lower frequency tones.
The range of human auditory frequencies spans 20–20,000 Hz, with speech fre-
quencies ranging from 400 to 5000 Hz, with the greatest loss in hearing seen in
frequencies greater than or equal to 2000 Hz. The loss of this linguistic information
results in many of the complaints in presbycusis. The loss of meaning is seen in
deterioration of speech intelligibility, the loss of clear separation between words
results in speech sounding mumbled, and the loss of syllables causes difficulty dis-
cerning similarly sounding words. Patients with presbycusis rely on conversational,
emotional, and postural context clues to compensate for their hearing impairment,
requiring a greater amount of higher order cognitive functioning to understand daily
conversations.

4.1.3.1 Osseointegrated Auditory Implants

Osseointegrated auditory implants like the bone-anchored hearing aid (BAHA) sys-
tems are approved in the United States for patients with single-sided deafness (SSD)
or those with a conductive/mixed hearing loss (CMHL) who cannot use traditional
amplification. The use of BAHA systems began in patients with dental implants.
4 Head and Neck in Geriatric Patients 81

These individuals noted the perception of sound through an osseointegrated dental

implant. BAHA systems use an external processor to amplify sound waves as vibra-
tions that are delivered to the inner ear. Older patients fitted with a BAHA experi-
ence substantially improved hearing and word and speech recognition and obtain
greater sound localization, and substantial numbers report improvement in quality
of life.

4.1.3.2 Cochlear Implantation

Although most older patients are appropriate candidates for amplification, up to
10% of older patients with hearing loss suffer from hearing loss severe enough that
amplification cannot provide significant benefit. Cochlear implants, devices placed
into the inner ear to restore the perception of sound, are an effective intervention for
older patients who do not benefit from amplification. Unfortunately, the rate of
cochlear implant use in older adults who meet candidacy criteria is less than 5%.
Outcomes of cochlear implantation are closely related to the duration of deafness,
and counseling patients and their families on reasonable expectations is essential.
Cognitive evaluations can help guide assessment and counseling. Cochlear implan-
tation is a surgery commonly performed under general anesthesia, lasting less than
2 h. Despite the short nature of the surgery, careful attention must be paid to medical
comorbidities [57–59].
Older cochlear implant users show greater confidence and participation in social
settings than they did preoperatively. Moreover, older cochlear implant users and
their families also reported high levels of satisfaction and hearing benefits from
their devices.
Radiologists play an essential role in the pre- and postoperative evaluation and
selection of CI candidates. Preoperative imaging is important to diagnose any type
of inner ear malformations and to identify other abnormalities in the temporal bone
that may be encountered. It allows the best insight into all relevant anatomical
details and potential situations which preclude surgery or require modifying stan-
dard surgical approaches. Postoperative imaging is important to confirm and docu-
ment the intended electrode position and to demonstrate any scalar dislocation,
cochlear dislocation, electrode fold, or malposition, which can be a possible source
of CI malfunction [60–62].
Preoperative imaging in CI candidates is based on high-resolution computed
tomography (HRCT) and magnetic resonance imaging.
The strength of HRCT is the detailed visualization of the bony structures of
the middle and inner ear, helping to determine the probability of success of the
procedure, influencing the choice of implants, and allowing the surgeon to choose
the best side of implantation. CT is ideal for ossific disease in chronic labyrinthi-
tis because such condition, if very extensive, can preclude the implantation
[63, 64].
An absent cochlear nerve, congenital or acquired, is the only complete contrain-
dication to successful cochlear implantation [65].
Bilateral acoustic and disruptive fractures of the cochlea are relative contraindi-
cation to implantation.
82 T. Popolizio et al.

a c

Fig. 4.3 External auditory canal exostoses—hearing loss. NCCT Ax (a) and Cor (b): broad-based
and focal circumferential bony overgrowth of the osseous external auditory canal causing stenosis
of the left auditory canal. Stenosis external acoustic. X-ray (c) of implant shows how well it is the
curve of the skull

MRI can visualize the fluid content of the membranous labyrinth. Visualization
of the vestibulocochlear nerve in the fluid-filled internal auditory canal and cerebel-
lopontine angle is only possible by the MRI [66, 67].
Postoperative imaging is required when a malfunction of the device is suspected
[63]. However, the authors perform—and recommend to do so—a postoperative
examination in every patient to confirm the correct position of the implant electrode.
Information regarding basal electrode location helps improving programming accu-
racy, associated frequency allocation, and audibility with appropriate deactivation
of extracochlear electrodes [68, 69].
Postoperative CT has turned out to be useful in visualizing position of the elec-
trode array by using HRCT or cone-beam computed tomography (CBCT).
Successful cochlear implantation requires that the electrode be confined to the scala
tympani. In general, CBCT is associated with lower dose and less metal artifacts
when compared to HRCT (Fig. 4.3) [70].

4.2 Nose

4.2.1 Rhinosinusitis

Based on the Medical Expenditure Panel Survey for 2007, which concerned
225.1 million Americans, Bhattacharyya estimated the prevalence of chronic rhino-
sinusitis (CRS) (with nasal polyps or without nasal polyps) at 0.2% or 490/10,000

AL GRAWANY
4 Head and Neck in Geriatric Patients 83

population. When analyzing the information obtained on 57,128 people aged

15–75 years who lived in 19 centers in 12 European countries, the Global Allergy
and Asthma Network of Excellence study concluded that the overall prevalence of
CRS, based on European position paper on rhinosinusitis and nasal polyps (EP3OS)
criteria, was 10.9% (range, 6.9–27.1%) [71, 72].
The size of the geriatric population is on the increase in developed countries: the
U.S. Census Bureau estimated that 20% of the U.S. population will be at least
65 years old by 2030. Recently, the prevalence of CRS among people 60 years was
calculated at 4.7%, and rhinosinusitis was judged to be the sixth most common
chronic condition in the elderly [73, 74].
There are several factors that predispose the elderly to chronic paranasal sinus
inflammatory disease. Age-related changes in the nasal and paranasal mucosa
include:

• An increase in the volume and a decrease in the elasticity of the nasal mucosa
[75, 76]
• A reduced or absent nasal cycle, partly due to a declining ciliary efficacy
• Atrophy of the supporting fibro fatty tissues of the nose, with a potential loss of
support for the nasal structures (narrowing of the nasal valve), which gives rise
to more nasal obstruction
• A higher incidence of rhinorrhea with more mucus due to increased glandular
activity and more viscous secretions and excess mucus crusting [77]

Aging in patients with CRS is also characterized by an increasing likelihood of

comorbid conditions and the use of several types of medication, such as bisphos-
phonates, non-steroidal anti-inflammatory drugs, antihypertensive agents, antide-
pressants, and vitamins.
There are several forms of chronic sinonasal inflammation including chronic
bacterial sinusitis, allergic sinusitis, fungal, and vasomotor sinusitis.
The two primary diagnostic imaging technique for evaluating the paranasal sinus
are CT and MRI [78].
The main role of CT is to aid the diagnosis and management of recurrent and
chronic disease, to define anatomy and to help the preoperative planning of
FESS. CT can differentiate pathologic variation and better shows, because of its 3D
high resolution, anatomic structures inaccessible by physical examination or endos-
copy [79].
CT is more readily available than MRI.
The use of a bone algorithm provides resolution of osteomeatal complex and
other anatomic factors. The characteristic findings include: air-fluid level, mucosal
thickening, and opacification of the normal aerated lume [80, 81].
CT is superior to MRI for the delimitation of the fine bone structures of the
infundibular complex, orbital lamina, orbital floor, and cribriform lamina [82].
MRI might be used to assess therapeutic success in patients with inflammatory
disease with the advantage of avoiding radiation exposure. It can be used in screen-
ing for foci of septic disease before implantation of organs and prostheses, in the
diagnosis of complication of sinus infection or FESS (Fig. 4.4).
84 T. Popolizio et al.

a b

c d

Fig. 4.4 Acute rhinosinusitis. NCCT bone algorithm, axial (a) and coronal MPR (b). The maxil-
lary sinus is filled with hypodense tissue that also involves the upper and middle ethmoid cells and
the sphenoid sinus. Focal interruptions of lamina papyracea, cribriform plate, orbital floor, and the
maxillary bone are evident. Reticulation of the medial intraorbitary fat tissue is present suggesting
involvement. On post-contrast T1-w MRI, axial (c) and coronal (d) images, the pathologic tissue
has low signal on T1-w and intermediate on T2-w (not shown), fuzzy margins and determines
structural bone changes and focal interruptions. Internal fluid components are present, which show
proton diffusion restriction on DWI (not shown), compatible with abscess. Also, there is involve-
ment of pterygopalatine fossa, infratemporal fossa, lateral pterygoid muscle, the choana, and the
let nasal cavities

4.2.2 Inverted Papilloma

Sinonasal inverted papilloma (IP) is one of the most common benign epithelial
tumors of the nose and paranasal sinuses. It accounts for 0.5–4% of all nasal tumors,
with a male/female ratio of 2–4:1.1 It originates from the Schneiderian membrane
that lines both nasal and paranasal areas. The invagination of such epithelial
4 Head and Neck in Geriatric Patients 85

membrane within the submucosal stroma is the typical histological aspect of this
tumor. The age at onset varies, but it is mostly encountered between the fifth and
sixth decades of life. Although the precise etiology is not clear, several external fac-
tors and a relationship with some subtypes of the human papilloma virus are reported
in almost 40% of patients. It has been suggested that sinonasal IP can progress to
squamous cell carcinoma; some recent articles stated that alteration of cell cycle–
related proteins may contribute to the malignant transformation from IP to squa-
mous cell carcinoma. As initially reported, the origins of tumor were observed in the
lateral nasal wall (82%), maxillary sinus (53.9%), ethmoid sinus (31.6%), frontal
sinus (6.5%), and sphenoid sinus (3.9%) [83–85].
The proposed treatment for IP has always been a radical surgical removal based
on the recurrence rates and the possibility of malignant transformation/association
with malignant lesions. As stated in the literature, we confirmed that the tumor pre-
sented a pedicle and a single site of attachment. The research of the pedicle’s attach-
ment is facilitated by radiological examination because, according to several recent
articles, the site of tumor attachment can be frequently predicted by both computed
tomography (CT) and magnetic resonance imaging (MRI) scans. Moreover, in most
cases, the tumor’s pedicle and the site of attachment can be accurately unveiled dur-
ing surgery, and the tumor’s extension can be precisely studied [86, 87].
Even though combined CT and MRI are useful for preoperative assessment of
sinonasal IP, differentiation of IP from other malignant sinonasal tumors is often
difficult because the overlap of imaging features. CT demonstrates soft tissue den-
sity mass with enhancement. The location of the mass leads toward the correct diag-
nosis. As the mass enlarges, it results in bony remodeling and resorption [85, 88, 89].
In 40% of cases, intralesional calcifications can be observed, representing resid-
ual bone fragments. The presence of focal hyperostosis has been correlated to the
point of origin of the lesions [90].
MRI often demonstrates a distinctive gross mucosal morphology of IP, called
convoluted cerebriform pattern (CCP), a “striated” imaging, seen on both T2 and
contrast-enhanced T1-weighted images, with characteristic alternating hypointense
and hyperintense bands.
In T1-weighted images, it appears isointense to muscle, in T2 generally hyperin-
tense to muscle with alternating lines. In roughly 50% of cases IP enhance, the
lesions are heterogeneous with alternating hypointense and hyperintense bands
[91, 92].
The presence of central necrosis requires consideration of an associated malig-
nancy [93–96].
IP can show an aggressive pattern of bone destruction because it may cross the
cribriform plate into the cranial anterior fossa.
They can erode the skull base comparable to aggressive cancer and because of
this signal intensity characteristics place on those of malignancies [97, 98].
Recurrences may be distinguished from postoperative thickening by dynamic
enhanced MRI because they have earlier and greater enhancement than granulation
tissue (Fig. 4.5) [99].
86 T. Popolizio et al.

4.2.3 Dacryocystitis

Dacryostenosis is an acquired or congenital condition that can cause epiphora but

can progress to dacryocystitis in children and in adults. This activity reviews the
pathogenesis, evaluation, and management of dacryostenosis infection and

a b

c d

Fig. 4.5 Inverted papilloma. NCCT axial (a) and coronal MPR reconstruction (b): expansive
dense mass in the left maxillary sinus erodes the lamina papyracea and invades the nasal fossa.
There are signs of bone remodeling (thinning and bowing) and resorption. The cribriform plate is
intact. On MRI, the lesion has low signal on T1-w (c), axial (d), and coronal (e) T2-w images
showing a “striated pattern” sign. On post-contrast T1-w MRI image (f), the lesion shows periph-
eral enhancement. DWI coronal image (g) shows restricted diffusion
4 Head and Neck in Geriatric Patients 87

e f

Fig. 4.5 (continued)

highlights the role of the interprofessional team in the care of patients with this
condition [100, 101].
The etiology of acquired dacryostenosis is multifactorial and is not fully under-
stood. Some cases may be related to trauma, neoplasm, systemic disease, radio-
therapy, or chemotherapy. However, in most cases, the cause is “involutional” and
classified as “idiopathic.” Some authors have reported that the cause is secondary to
anatomic changes in the diameter of the bony lacrimal canal, which occurs with
aging. Women, in particular, have a smaller diameter of the lacrimal duct that tends
to narrow with time. A congenital narrowness within the lacrimal drainage system
is generally regarded as a disposition for lacrimal stenosis [102].
88 T. Popolizio et al.

Some authors suggest that the cause may be from ascending inflammation from
the region of the nose and sinus cavities. A descending infection from the conjunc-
tiva has also been suggested as a cause of acquired dacryostenosis. Clinical studies
indicate that nasal disease is sporadic in patients undergoing DCR [103].
Familial predisposition and osteoporotic changes have also been suggested as
being predisposing factors.
The obstruction is more frequently situated at the level of the nasolacrimal duct
or puncta and less frequently at the level of the canaliculi. The incidence is higher
among older people and in women [104].
Diagnosis is usually made clinically; however, imaging may help to exclude
complications. It is important distinguishing between acute and chronic dacryocys-
titis [100].
Acute dacryocystitis is commonly associated with preseptal cellulitis.
Complications include orbital cellulitis (limited to preseptal tissues), corneal
involvement, lacrimal sac mucocele and, rarely orbital abscess. The most common
organisms implicated are Staphylococcus aureus in acquired cases and S. pneumo-
nia in congenital cases although cultures and smears expressed punctual secretions
as desirable [105].
Chronic dacryocystitis is a result of chronic obstruction due to systemic disease,
repeated infection, dacryoliths, and chronic inflammatory debris of the nasolacrimal
system. Some common systemic diseases include Wegener’s granulomatosis, sar-
coidosis, and systemic lupus erythematosus.
Acquired states are typically due to repeated trauma, surgeries, medications, and
neoplasms. Among traumatic causes of nasolacrimal obstruction, nasoethmoid frac-
tures seem to be most common.
Imaging features pointing to acute dacryocystitis include thick rim enhancement
and extensive adjacent soft tissue preseptal cellulitis.
MRI is the imaging modality of choice in the evaluation of orbital cellulitis
because of its superior soft tissue and contrast resolution. It is essential to evaluate
the extent of the orbital infection, underlying paranasal sinus involvement, as well
as detect complications of orbital cellulitis, especially intracranial spread. Orbital
cellulitis causes diffuse, edematous infiltration of the orbital connective tissue that
is best demonstrated by the high signal intensity in T2-weighted fat-saturated
sequences. Other findings are swelling and ill-defined margins of the extraocular
muscles and exophthalmos. Orbital cellulitis may be complicated by an abscess,
which may form in the extraconal or intraconal orbit separate from the bone.
Periorbital cellulitis is a preseptal process, which is limited to the soft tissues
anterior to the orbital septum. It usually occurs due to the contiguous spread of
infection from adjacent structures such as the teeth and face. Computed tomography
and MRI demonstrate diffuse soft tissue thickening anterior to the orbital septum.
Infection in orbit, whether as a result of periorbital cellulitis extending across the
orbital septum or due to sinusitis, constitutes an emergency.
MRI is better than CT, in fact it provides excellent contrast resolution in the orbit
with the demonstration of pathologies in the intraconal and extraconal compart-
ments. The ability to depict cross-sectional anatomy and pathology with better tis-
sue characterization and even without administering intravenous gadolinium-based
4 Head and Neck in Geriatric Patients 89

a b

Fig. 4.6 Dacryocystitis. NCCT Ax (a), e Cor MPR reconstruction (b). Well-circumscribed round
lesions with fluid core around the inner canthus, with adjacent soft tissue thickening and fat strand-
ing, scalp melanoma is noticed

contrast agent is a distinct advantage of MRI over CT scanning, especially intracra-

nial spread.
Although T1-weighted contrast-enhanced imaging with fat suppression is widely
held as the gold standard in the detection and characterization of orbital pathology,
T2-weighted fat-suppressed sequences have similar sensitivity for detecting orbital
lesions and readily identify postseptal disease. Contrast enhancement, however, is
essential for distinguishing abscess from edema and phlegmon.
Abscesses show a well-described phenomenon of diffusion restriction, likely
related to the viscosity and dense cellular packing purulent material, strongly hyper-
intense on trace DW images and with reduced apparent diffusion coefficient (ADC)
images within the central, non-enhancing portion of the abscess cavity (Fig. 4.6).

4.3 Skin Tumors

Cutaneous squamous cell carcinoma (cSCC) accounts for approximately 20% of all
non-melanoma skin cancers, which is the most common malignancy worldwide.
Although less than 5% of head and neck cSCC (HNcSCC) metastasize, lymph
node metastases in the parotid and/or neck are potentially lethal and require morbid
multimodal regional therapy with surgery and adjuvant radiotherapy (RT). Although
the fundamental treatment approach has remained largely unchanged, there have
been several advances that may impact survival.
There have been very few studies examining trends in survival of HNcSCC, par-
ticularly metastatic HNcSCC. Gnanasekaran et al. recently examined the trends in
prognosis of patients with metastatic HNcSCC over the last 30 years within a single
Australian institution. The authors reported improved cancer-specific survival over
90 T. Popolizio et al.

time despite treating increasing numbers of elderly patients and more aggressive
cancers.
The radiologist’s roles include evaluating the full local extent of the primary,
detecting perineural tumor, and assessing regional nodal and distant spread of disease.
CT scanning or MRI can be helpful in defining the extent of disease. CT scan-
ning is useful for determining the presence of bone or soft tissue invasion and for
evaluating cervical lymph nodes at risk for metastasis.
cSCCs predominantly exhibited a flattened configuration, superficial ulcer for-
mation, protrusion into the subcutaneous tissue, ill-demarcated deep tumor margin,
and peritumoral fat stranding.
Conventional MRI sequences are also superior to CT for a variety of findings that
influence the therapeutic choice such as laryngeal cartilage invasion, invasion of the
skull base, perineural spread, detection of retropharyngeal lymph nodes in nasopha-
ryngeal carcinoma, extranodal spread in metastatic neck nodes and vascular and
lymphatic invasion.
On T2-weighted MRI the show ill-demarcated, flattened, cutaneous lesion, with
superficial ulcer formation and protrusion and infiltration into subcutaneous fat tis-
sue. Fat-suppressed T2-weighted image is useful for the evaluation of peritumoral
fat stranding. MRI criteria based on the analysis of signal intensity and enhance-
ment patterns after injection of gadolinium have had a major impact on the assess-
ment of deep tumor spread. In most HNSCCs, the actual invasion of bony and
cartilaginous structures is often preceded by tumor-induced inflammation. In laryn-
geal and hypopharyngeal HNSCCs, careful analysis of signal intensities on T1 and
T2 sequences has improved differentiation between tumor and inflammation: mod-
erate enhancement on T1 and moderately high signal on T2 indicate tumor involve-
ment, whereas high signal on T2 and vivid enhancement correspond histologically
to peritumoral inflammation (Fig. 4.7).

Fig. 4.7 Contrast

enhancement CT (CECT)
scan: subcutaneous
expansive lesion with avid
contrast enhancement and
central necrosis that
infiltrates fat and the
aponeurosis
4 Head and Neck in Geriatric Patients 91

4.4 Tumors of the Oral Cavity

The population in developed countries is aging rapidly, which is associated with a

significant increase in the total cancer burden over the last decades and, specifically,
also with an increase in the incidence of the head and neck squamous cell carcinoma
(HNSCC) after 50 years of age. Although the age of most of the HNSCC patients
ranges between 50 and70 years, the occurrence of this tumor type in older patients
is not rare.
The medical literature provides no clear definition of an elderly person. According
to the National Institute on Aging and the National Institutes of Health, elderly per-
sons can be classified into three categories: young old, aged 65–75 years; old, aged
76–85 years; and oldest old, older than 85 years.
Because aging is a highly individualized process and the elderly population is
very heterogeneous, chronological age alone is an inappropriate parameter for treat-
ment selection. More important is functional age, which should be defined individu-
ally for each patient based on the functional status, comorbidities, and presence of
geriatric syndromes. Several authors concluded that traditional oncology measures
of functional status alone (e.g., Karnofsky performances status score) do not appear
to reflect the comorbidity burden and its prognostic potential in elderly patients. A
long-lasting history of tobacco and alcohol abuse that is characteristic for a substan-
tial proportion of HNSCC patients, an advanced age per se, and the history of other
factors or events increase the probability for severe comorbidity. According to lit-
erature, the prevalence of comorbidity in the general population of HNSCC patients
is approximately 60%, whereas the rate of moderate and severe comorbid burden is
in the range of 20%. As may be expected, these figures rise with age, impacting the
prognosis of the patients significantly and independently from other factors. In older
patients with cancer, a full onco-geriatric evaluation is warranted prior to any treat-
ment decision-making to avoid overlooking any relevant information about the abil-
ity of an older patient to cope with the proposed treatment. This assessment is
probably the most critical step, as its results have a profound effects on all down-­
stream decisions (i.e., the aim of treatment—palliation vs. curative, the extent of
diagnostics and mode(s) of therapy employed) and, thus, also on the prognosis.
Unlike other evaluation instruments, which are mostly focused on some specific
issues, the CGA uses standardized instruments to employ a multidimensional and
interdisciplinary approach. The CGA encompasses a spectrum of important clinical
domains, namely an evaluation of different aspects of patient functioning, comor-
bidity, polypharmacy, nutritional status, cognitive function, socio-economic issues,
and geriatric syndromes, thus allowing for the identification of patient groups with
different frailty levels and selection of the appropriate therapeutic strategy.
There are features distinctive for HNSCC patients of older age groups. First of
all, in the elderly, there is a significantly higher proportion of female patients com-
pared to the younger population. The reason for this is most probably longer life
expectancy among females. In addition, a history of alcohol abuse and smoking is
less frequently reported in the advanced age groups than in the general population
of HNSCC patients [106].
92 T. Popolizio et al.

The most prevalent primary tumor sites in the head and neck region in
elderly patients seem to be—depending on the series—the oral cavity or the
larynx, each comprising up to one half of all primaries, with the tendency to
overcome their incidence among younger-aged patients. A trend of fewer hypo-
pharyngeal cancer cases in the elderly patient group was also observed.
Considering the tumor stage at presentation, it appears that the occurrence of
an advanced disease (T3, T4) at the primary site is comparable to or even
reduced when matched with that observed in younger age groups, but the
regional lymphatics are primarily less frequently infiltrated by cancer cells in
older patients. Apparently, an increase in the disease severity that would be
expected from the usual delay in diagnosis in older people, probably reflecting
age-related inequalities in access to health care due to a variety of social and
behavioral factors is successfully compensated by a less aggressive biology of
the disease in the elderly [107–109].

4.5 Salivary Gland Tumors

Incidence of benign and malignant salivary gland tumors in major portion of the
world ranges from 1 to 2 cases per 100,000 people per year There is no specific
predilection of occurrence of these tumors in any particular gender, although
Warthin’s tumor is more common in males and acinic cell tumor in females. Site-­
wise incidence varies for both benign and malignant tumors. Seventy-five to eighty
percent of benign tumors occur in the parotid glands, 5–10% in submandibular
glands, and only 1–2% in sublingual glands. Malignant tumors are more common in
sublingual glands (80%) and least in parotid glands (17–20%). Benign tumors affect
a mean age group of 40 years, and malignant tumors affect an age group of 55 years
[110–114].

4.5.1 Pleomorphic Adenoma

Most frequently found in the superficial lobe of the parotid gland, it presents as a
firm, slow-growing asymptomatic mass which is smooth, rounded, lobular, and
mobile with a rubbery consistency causing ear lobule to be raised [115, 116].
On light microscopy, morphologically complex and diverse cellular elements are
seen. Both epithelial and myoepithelial elements are present myxoid to extreme cel-
lular [117].
Surgical excision is the treatment of choice. Historically, enucleation was prac-
ticed which resulted in inadequate surgery and recurrences. Superficial parotidec-
tomy is the most widely accepted technique in the treatment of pleomorphic
adenomas in the superficial lobe of the parotid gland, and total gland excision with
facial nerve preservation is carried out [118, 119].

AL GRAWANY
4 Head and Neck in Geriatric Patients 93

4.5.2 Warthin’s Tumor

Warthin’s tumor, also known as papillary cystadenoma lymphomatosum and adeno-

lymphoma, is the second most common benign tumor of the salivary glands, around
5% of neoplasms [120].
The majority of the tumors arise in the parotid gland, more often bilaterally, in
the elderly and occurs in the fifth and sixth decades of life. A predilection for male
sex is seen, more in Caucasians. Both the tumors do not occur simultaneously but
are metachronous in their manifestation.
Surgical removal is the established treatment for Warthin’s tumor. Treatment phi-
losophies given are:
• Tumor enucleation with resection of minimal amount of surrounding nor-
mal tissue
• Superficial parotidectomy, which is more aggressive than enucleation
• Local excision of parotid gland [121, 122]

4.5.3 Mucoepidermoid Carcinoma

Mucoepidermoid carcinoma is the most common malignant salivary gland neo-

plasm. They are classified as grade I (low grade) which are well differentiated,
grade II (intermediate grade) which are moderately differentiated, and grade III
(high grade) which are poorly differentiated tumors [107, 123–126].
Mucoepidermoid carcinomas occur more commonly in the minor salivary glands
with a female predilection.
It occurs as a painless, circumscribed, mobile solitary enlargement of the body or
tail of the parotid or the submandibular region with over a year duration generally.
Complete, adequate, and radical surgical excision is the treatment of choice for
all grades of mucoepidermoid carcinomas.

4.5.4 Adenoid Cystic Carcinoma

Adenoid cystic carcinoma (ACC) is a highly aggressive, destructive, and clinically

unpredictable tumor of the head and neck region.
Adenoid cystic carcinoma occurs in adults between 50 and 70 years of age with
equal prevalence in males and females.
Clinically adenoid cystic carcinoma manifests in the major and intraoral acces-
sory salivary glands as a slow growing swelling or mass.
Histopathologically, ACC are classified into cribriform pattern, tubular pattern,
and solid pattern. A major microscopic feature in most adenoid cystic carcinomas is
the propensity for the tumor to involve peripheral nerves, reported to occur in
20–80% of the patients.
94 T. Popolizio et al.

Complete excision like all other tumors is the treatment of choice. Elective
regional lymph node dissection is not indicated, because distant metastasis is more
common than cervical (regional) node involvement [127–131].

4.5.5 Squamous Cell Carcinoma

The diagnosis of primary squamous cell carcinoma is limited to the major glands.
It occurs between 7 and 95 years of age, the mean age being 60.5 years with a
male predilection of 2:1. Parotid gland is the most commonly involved followed by
submandibular and sublingual glands [132].
Surgical management is the mainstay of treatment. Parotidectomy with or with-
out facial nerve preservation depending on the case is needed for parotid tumors.
Submandibular sialoadenectomy is needed for submandibular gland tumors. A neck
dissection is done in clinically positive necks at the slightest suspicion [116].

4.5.6 Pleomorphic Adenoma

Pleomorphic adenoma is the most common salivary gland tumor and is character-
ized by cytomorphological and architectural diversity. On CT and MR images, PAs
are shown as well-circumscribed rounded masses, most commonly located within
the parotid gland, sometimes joined by characteristic lobulated contour enhance-
ment. On T2-weighted images, typical PAs show marked hyperintensity, which
reflects the abundant myxochondroid stroma, with a hypointense rim indicating the
fibrous capsule. The intensity signal within the tumors varies due to the cellular
density, proportion of epithelial and stromal components, and type of stromal com-
ponents. In addition, a variety of secondary histological changes, including fibrosis,
lipometaplasia, ossification, cystic degeneration, and infarction, occur rarely in PAs.
T1-weighted images after contrast administration usually demonstrate homoge-
neous enhancement [133, 134].

4.5.7 Whartin’s Tumor

It is the second most common benign tumor arising in the parotid gland after benign
mixed tumor. On CT, Warthin’s tumors usually appear as small (2–4 cm, rare
>10 cm), ovoid, smoothly marginated masses. They are homogenous soft tissue
density lesions without calcifications. Cyst formation with homogenous material is
common (30%). The cyst wall is usually thin and fairly smooth. The presence of a
mural nodule helps to distinguish Warthin’s tumors with large cystic components,
septa or multiple adjacent cystic lesions from first branchial cleft cysts or lympho-
epithelial cysts [135–137].
4 Head and Neck in Geriatric Patients 95

On MRI solid and cystic components show low T1-weighted signal, but
cystic areas may show high signal secondary to proteinaceous debris and/or
hemorrhage. In T1-weighted images after contrast administration solid compo-
nents show minimal contrast enhancement. In T2-weighted images, solid com-
ponents appear intermediate to high signal, with high signal in cystic foci,
intermediate signal in Proton Density-weighted images, while in STIR images
the lesions become more conspicuous, especially the cystic components.
Warthin’s tumors show significant restriction of diffusion. The differential
diagnosis of Warthin’s tumor includes benign mixed tumor, benign adenopathy,
lymphoma, benign lymphoepithelial lesions—HIV, adenoid cystic or mucoepi-
dermoid carcinoma, as well as squamous cell carcinoma and melanoma nodal
metastasis [138–140].

4.5.8 Mucoepidermoid Carcinoma

MEC has been classified histologically as low, intermediate, or high grade accord-
ing to intracystic components, mitotic figures, neural invasion, necrosis, and cellular
anaplasia.
MRI findings are variable reflecting their histological nature, which seems to
have certain tendencies depending on the tumor grade.
Tumors show inhomogeneous low to intermediate signal intensity on
T2-weighted images, reflecting high cellularity, with an ill-defined margin, reflect-
ing peritumoral inflammatory changes rather than invasive tumor growth. In the
intermediate-grade MECs, tumors showed intermediate signal intensity on
T2-weighted images. Among the low-grade MECs, most tumors had a hyperin-
tense area on T2-weighted images because of the existence of abundant mucin-
secreting cells. High-grade tumors, on the other hand, have lower signal on T2 and
poorly defined margins and infrequent cystic areas. On T1 images following
administration of contrast, there is heterogeneous enhancement of solid compo-
nents [141–144].
Lymph node metastasis was seen often in high-grade MECs.
On CT images, low-grade tumors appear as well-circumscribed lesions, usually
with cystic components. The solid components enhance and calcification is some-
times seen. They have appearances similar to benign mixed tumors. High-grade
tumors have poorly defined margins, infiltrate locally, and appear solid.

4.5.9 Adenoid Cystic Carcinoma

Adenoid cystic carcinoma has a propensity for perineural spread. A high-grade vari-
ant is evidenced by a copious of pleomorphic cells, loss of the classic biphasic
epithelial-­myoepithelial growth pattern, and comedonecrosis. CT and MRI are
96 T. Popolizio et al.

considered reliable and convenient methods for diagnostic and prognostic predic-
tion, they can both be helpful for demonstrating the extent of invasion in oral cavity-­
associated adenoid cystic carcinoma, which can reach the inferior alveolar nerve for
perineural spread by direct invasion through the mandible. It is usually best depicted
on MRI. Low-grade tumors tend to be well-defined, in contradistinction to high-­
grade tumors, which appear infiltrative. However, on T1-weighted images both the
subtypes are usually hypo to isointense, on T2 slightly hyperintense, with higher
grades being markedly hypointense and homogeneously enhancing after contrast
administration. In particular, involvement of cranial nerves and tumoral infiltration
around the nerves and osseous structures is optimally assessed via non-contrast
T1-weighted and contrast-enhanced, fat-suppressed T1-weighted MR sequences.
Perineural spread typically appears as enlargement and abnormal enhancement of
the affected nerve and widening or obliteration of the nerve canal. Considering ade-
noid cystic carcinoma of the oral cavity can attain, overrun, and infiltrate the inferior
alveolar nerve by first eroding through the mandibular cortex, and infiltrating
through the bone marrow, CT can be complementary to MRI.

4.5.10 Squamous Cell Carcinoma

MRI features showed large tumor size, irregular shape, ill-defined margin, extrapa-
rotid infiltration, low-intermediate signal intensity in the solid portions on
T2-weighted images and the presence of central necrosis. On contrast-enhanced
T1-weighted image with the fat-suppression technique, the mass has a central unen-
hanced area and can infiltrate the subcutaneous fat, mandibular ramus, and parapha-
ryngeal space.
The ill-defined margins and extraparotid infiltration, which reflect the invasive
growth of the tumor cells. The appearances of SCC originating in the parotid gland
on MRI can be similar to other more common parotid malignancies (e.g., adenoid
cystic carcinoma and muco-epidermoid carcinoma) (Figs. 4.8 and 4.9) [125, 145].

Fig. 4.8 Parotid gland adenocarcinoma. CECT (a) shows an expansive lesion with avid enhance-
ment located in the superficial lobe and in the deep portion of the gland. Peripheral stranding and
central fluid areas are evident. MRI confirms the presence of an infiltrating lesion with fuzzy bor-
ders that shows isointense signal on T1 (b) and low signal on T2-w (c) and high contrast enhance-
ment on post-contrast T1-w (d). Irregular stranding can be appreciated in the adipose tissue around
and posteriorly to the deep portion on the gland (sagittal post-contrast T1-w (e and f)). Bulky and
coalescent nodal metastases are also present
4 Head and Neck in Geriatric Patients 97

a b

c d

e f
98 T. Popolizio et al.

a b

c d

Fig. 4.9 Parotid gland cystadenoma. The MRI shows expansive lesion located in the deep part of
the parotid gland that deforms its contour and comes close to the external carotid and the internal
jugular vein, without imaging findings of infiltration. The lesion has high signal intensity on T2-w
(a) with an isointense small central component with corresponding high signal intensity on fat
saturated T1-w without contrast (b), suggesting proteinaceous components. On post-contrast T1-w
(c), contrast enhancement is avid in the deeper part of the lesion, while it is more nuanced and
inhomogeneous in the superficial portions. A fluid component with peripheral enhancement is also
noticed. On DWI (d) the lesion shows restriction in the diffusion of proton density. There are also
two lymph nodes in the superficial layers of the gland

4.6 Osteonecrosis

The bisphosphonates play a major role in the treatment and prevention of these
skeletal related events, together with radiation therapy, surgery, analgesics, and
standard anticancer therapy. The primary goal of these therapeutic strategies is to
4 Head and Neck in Geriatric Patients 99

improve the quality of life, as the disease is usually incurable at this stage. The
occurrence of osteonecrosis of the jaw (ONJ) associated with the use of bisphospho-
nates is a potentially new side effect that can have a severe impact on the daily
functioning of the affected individuals, causing great concern among patients, den-
tists, and the medical community [146–148].
Osteonecrosis of the jaw has historically been linked with exposure to white
phosphorous (“phossy jaw”) and in more recent times with radiotherapy and
chemotherapy.
Changes in the socioeconomic fabric of society, resulting in safer working envi-
ronments and the banning of white phosphorus, have caused phossy jaw to be noth-
ing more than a historical curiosity. Osteoradionecrosis, on the other hand, is a
well-defined entity that can be adequately managed with combined hyperbaric oxy-
gen therapy and surgery, although it can develop many years after initial treatment
[6]. Chemotherapy as a cause of ONJ has been infrequently reported in the literature
and is poorly understood, but the presence of infection and dentures seems to be
important in the development of this disorder.
Diagnostic criteria put forward by an expert panel have been published and con-
firm ONJ as a clinical diagnosis. The disorder is defined as the persistence of
exposed bone in the oral cavity after adequate treatment for 6 weeks, in the absence
of local metastatic disease and without previous radiation therapy to the affected
area. This definition is, however, deceptively simple, as the differentiation between
osteonecrosis complicated by infection and osteomyelitis with secondary osteone-
crosis can be difficult, if not impossible. Although these criteria will help uniform
reporting, there is some ambiguity regarding the role of other diagnostic proce-
dures, such as pathology, imaging, and microbiology. Moreover, it is unclear what
an “adequate treatment” should entail [119, 149].
Clinical examination reveals an exposed alveolar ridge with sequestra of necrotic
bone, often with a foul smelling discharge. The surrounding gingival and mucosal
tissues are usually inflamed and painful to touch. The lesions can become multiple,
as one study identified 2.3 areas of ONJ per patient. The mandible is affected in the
majority of cases (60–80%), with the lingual posterior area being particularly sus-
ceptible, which may relate to the thinness of the mucosa in this region and can be
easily traumatized during normal mastication. Fistulization to the maxillary sinus
and the skin can occur and pathological fractures of the mandible have also been
reported [150].
The aspect of ONJ at radiography, CT, and MR imaging is variable and is non-
specific at both anatomic imaging and functional imaging. Imaging takes part in
determining the extent of the disease, diagnosing early stages of osteonecrosis,
identifying a potential association between metastasis to the jaw and ONJ lesions,
excluding other diseases of the jaws, diagnosing complications such as fractures,
and evaluating the jaw before performance of orofacial procedures [151].
The appearance of ONJ at radiography and CT is variable and includes ill-­
defined areas of lucency or low attenuation, permeative appearance, cortical destruc-
tion, bony sequestrum, periosteal reaction, or sclerotic changes [152].
100 T. Popolizio et al.

The bone changes may be mixed, predominantly lytic or prevalently sclerotic.

The lytic areas may represent foci of bacterial infection. Persistent alveolar sockets
have been described as a typical radiographic feature of ONJ [153].
On MRI ONJ shows in T1-weighted images decreased marrow signal intensity,
in T2-weighted images has increased marrow signal intensity, and in contrast-­
enhanced fat-saturated T1-weighted images shows enhancement of marrow and soft
tissue and associated increased signal intensity and soft tissue prominence
(Fig. 4.10) [148].

b c

Fig. 4.10 Osteonecrosis. Patient with history of retromolar trigone carcinoma that underwent
surgery and radiation therapy. Orthopantomography (a) documents fixation device in the left man-
dibular bone and the presence of osteolysis discontinuity of bone fragments. Tumefaction of
adjoining small parts is also evident. NCCT with bone algorithm (b) better demonstrates bone
rarefaction and microfractures. On PET 18F-FDG (c) there is high metabolic activity (SUV max
7.09) suggesting inflammation
4 Head and Neck in Geriatric Patients 101

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Heart Diseases in Geriatric Patients
5
Anna Palmisano, Raffaele Ascione, Francesco De Cobelli,
and Antonio Esposito

5.1 Introduction

In the United States (US), adults aged ≥75 years represent 6% of the entire popula-
tion and the number of US citizens older than 80 years is expected to rise approxi-
mately by 25 million in the next 30 years.
Cardiovascular disease is the most frequent single cause of death in persons over
65 years of age, and more than 60% of myocardial infarctions occur in patients over
75 years of age [1]. The increase in life expectancy will likely cause an increase in
myocardial infarction cases [2]. Cardiovascular diseases such as coronary artery
disease, arrhythmias, heart failure and valve disease increase in incidence with
increasing age [3]. Age itself affects cardiac physiology and remodelling, making
challenge to distinguishing age-related changes to pathology. Main cardiovascular-­
related changes included increased diffuse fibrosis causing cardiovascular stiffness
with reduced vascular compliance, ventricular diastolic and systolic dysfunction,
and alteration in conduction system; increased lipid endothelial deposition with pro-
gressive atherosclerosis and fibrocalcific valve degeneration.
Cardiac Computed Tomography (CCT) and Magnetic Resonance Imaging (MRI)
are able to provide a deep characterization of myocardial anatomy, function and
remodelling, crucial for screening, diagnosis, risk stratification and therapy guid-
ance. Furthermore, imaging has a pivotal role in planning of interventional proce-
dures, rapidly developed in the last years aimed to safely treat more fragile patients

A. Palmisano · F. De Cobelli (*) · A. Esposito

Clinical and Experimental Radiology Unit, Experimental Imaging Center, San Raffaele
Scientific Institute, Milan, Italy
School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
e-mail: [email protected]; [email protected]; [email protected];
[email protected]
R. Ascione
Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 109
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_5
110 A. Palmisano et al.

[4]. The understanding of cardiac disease typically occurring in elderly and the
potential value of each cardiac imaging modality may help to decide on the most
suitable imaging modality and its timing [5]. This chapter provides an overview of
cardiac imaging modalities for the most frequent cardiovascular diseases in the
elderly population.

5.2 Coronary Artery Disease

5.2.1 Introduction

Coronary artery disease (CAD) constitutes one of the main causes of mortality in
the Western world. Many important studies such as the NHANES (National Health
and Nutrition Examination Survey), the FHS (Framingham Heart Study), MESA
(Multi-Ethnic Study of Atherosclerosis) and the CHS (Cardiovascular Health
Study) stated that the prevalence of CAD drastically increases in the elderly popu-
lation with men affected more than women [6–8]. The development of an athero-
sclerotic plaque in the intima of the coronary arteries is the primary cause of the
disease. The majority of coronary atherosclerotic plaques will not determine any
symptoms; however, some can clinically manifest in various forms that are gener-
ally classified as chronic coronary syndrome (CCS) and acute coronary syn-
drome (ACS).
CCS include the so-called Stable Angina in which thoracic pain is exacerbated
by the presence of an atherosclerotic plaque in the intima layer of the coronary
arteries which induces significant stenosis of the coronary lumen and reduction of
blood flow supply. This results in faster exhaustion of the coronary flow reserve and
the subsequent insufficiency of oxygen supply to the myocardium, which typically
occurs after physical exercise or in any situation with increased oxygen demand.
ACS is commonly triggered by the rupture or the erosion of the fibrous cap of an
atherosclerotic plaque, which leads to rapid platelet aggregation and thrombus for-
mation. This can determine a sudden variable degree of obstruction to the coronary
blood flow with downstream myocardial damage, resulting in three different clini-
cal manifestations: unstable angina, non-ST-elevation myocardial infarction
(NSTEMI), or ST-elevation myocardial infarction (STEMI). In some cases, sudden
arrhythmic death may be the first clinical manifestation of CAD.

5.2.2 CAD Pathophysiology

Atherosclerosis is a slow pathophysiological process that probably begins in the

first stages of life and involves the deposition of lipids, fibrous tissue, smooth mus-
cle cells, and calcium in the intimal layer of coronary arteries [9]. Atheroma gener-
ally forms in proximal coronary segments and vessel bifurcations [9, 10].
Acute coronary syndromes typically occur following the rupture or the erosion
of a vulnerable plaque with subsequent thrombosis and occlusion of the vessel
5 Heart Diseases in Geriatric Patients 111

lumen. Often, these plaques are not associated with relevant luminal stenosis and
exhibit a thin, fibrous cap with a large necrotic core. Other typical features of vul-
nerability are plaque vascularization, high plaque volume, matrix metalloproteinase
expression and collagenase activity, and macrophage infiltration of the fibrous
cap [11].
Complete vessel occlusion can result in myocardial necrosis and subsequent
STEMI or NSTEMI, whereas partial vessel occlusion can lead to ischemia without
myocardial necrosis that clinically manifest as unstable angina [12].
However, the majority of atherosclerotic plaques remain clinically silent. These
slow-growing plaques induce progressive vessel stenosis with flow-limiting condi-
tion, whose symptoms eliciting stable coronary artery disease became manifest dur-
ing physical exercise and all condition requiring an increased oxygen demand for a
mismatch between the myocardial oxygen demand and myocardial oxygen con-
sumption. The reduction of coronary flow reserve is proportional to the degree of
luminal narrowing; however, it is further worsened by the endothelial dysfunction,
which typically occur in atherosclerosis causing impaired vasodilation indepen-
dently by the degree of stenosis.

5.2.3 Multimodality Imaging with a Particular Focus

on CT and MRI

Cardiac imaging can be used to unravel the coronary artery disease by either trig-
gering the ischemic process or via the direct visualization of coronary artery steno-
ses [13].
The majority of coronary stenosis do not cause ischemia and consequently do not
require revascularization. Ischemia was found in approximately 50% of patients
with obstructive CAD (stenosis ≥ 50%); therefore, the functional significance of
stenosis should be considered uncertain, and an imaging-based stress examination
is frequently required to identify myocardial ischemia in the setting of CCS [14].
Ischemia can be triggered by physical exercise or pharmacologic stress [15]. Single-­
photon emission computed tomography (SPECT), positron emission tomography
(PET) myocardial perfusion, stress echocardiography, stress computed tomography
and stress magnetic resonance (MR) imaging are the most commonly used tests
[16]. Recent studies stated that the Stress MRI and PET have similar accuracy and
are suitable to rule out hemodynamically significant coronary artery diseases in a
wide range of pre-test probability, while stress SPECT and echocardiography are
less reliable [17]. Stress MRI has also the advantage, over PET, of combining a
multiparametric characterization of the myocardium.
The direct visualization of coronary anatomy can be obtained invasively with
coronary angiography (ICA) or non-invasively with coronary computed tomog-
raphy angiography (CCTA). ICA offers the best spatial resolution and can be
combined with the measurement of the fractional flow reserve (FFR) to quantify
the stenosis significance and guide revascularization if its value is lower than
0.8 [16].
112 A. Palmisano et al.

In the recent years, CCTA emerged has a valid alternative to ICA in patients with
low-intermediate likelihood for CAD thanks to its negative predictive value close to
100% [13]. Despite CCTA is a pure anatomic method, the continuous technical and
methodological development opened the possibility of a CT-based assessment of func-
tional significance of stenosis using CT stress perfusion or non-invasive virtual FFR.
Each of the outlined strategies presents certain limitations. Ischemia testing has
limited sensitivity and specificity, cannot identify where coronary plaques are
located, and cannot perform stenosis grading and plaque characterization. Invasive
coronary angiography is associated with potential complications for its invasiveness
and high radiation exposure, as well as higher costs compared to non-invasive tech-
niques. CCTA can suffer from poor image quality in patients with arrhythmias or
tachycardia or can be misinterpreted determining false-positive results in case of a
very high calcium burden [13].
For these reasons, choosing the best imaging strategy must take into account
patient characteristics, pre-test probability, medical expertise and available tech-
nologies, preferring a non-invasive anatomical imaging strategy (CCTA) in case of
no previous history of CAD, low to intermediate clinical likelihood and when infor-
mation about the presence and the burden of coronary atherosclerosis is desired to
tailor the patient management.
While the use of imaging is well established for diagnosing CAD in symptomatic
patients, its role in primary prevention is still unclear. In asymptomatic individuals,
traditional risk factors such as hypertension, diabetes mellitus, sex and family his-
tory are used to estimate the risk of future major cardiac events and the need for
risk-lowering treatments. Non-enhanced cardiac CT has a crucial role in risk strati-
fication via the evaluation of coronary calcium score and will be discussed in the
following sections.
Non-invasive cardiac imaging has limited role in the setting of acute coronary
obstruction [18, 19], but has gained a growing role in patients with low-risk acute
chest pain or with a clinical-angiographic diagnosis of Myocardial Infarction with
Non-Obstructed Coronary Arteries (MINOCA).
CCTA has rapidly gained a central role to rule out CAD in patients with acute chest
pain and a relatively low pretest probability of ACS. However, it cannot exclude other
important causes of acute chest pain with unobstructed coronaries, such as acute myo-
carditis, myocardial infarction with normal coronary arteries, and cardiomyopathies.
A few recent studies showed the possibility to obtain information about myocardial
scar and extracellular volume also in CT; however, these techniques still need experi-
enced readers [20–22] and require large studies to define its generalizability.
Cardiac MRI is widely adopted in patients with non-obstructed coronary arteries
at ICA, being able to provide differential diagnosis of ACS impacting on patients’
treatment and management. Moreover, it plays a role in patients risk stratification
and in the diagnosis of complications [18].

5.2.3.1 CCTA
Minimum technological requirement and patients’ preparation are crucial to obtain
a diagnostic image quality. 64-detector row CT is considered the minimum standard
for CCTA.
5 Heart Diseases in Geriatric Patients 113

Image quality improves substantially when the heart rate is regular and lower
than 65 beats/min. In the absence of contraindication, the administration of beta-­
blockers and nitrates to lower the heart rhythm and to vasodilate coronary arteries is
recommended to improve image quality and coronary evaluation. Different acquisi-
tion strategies are available to obtain the best image quality based on patient’s heart
rate, BMI and ability to breath-hold. In general, retrospective ECG-gated helical
acquisition enables the reconstruction of image data sets at arbitrary time points
during the cardiac cycle. This technique provides excellent flexibility for identify-
ing the optimal cardiac phase without motion artefacts at the cost of higher radiation
exposure. Prospective ECG-triggered acquisition substantially reduces radiation
exposure but requires a lower and regular heart rate.
In the elderly population, considering the lower impact of radiation exposure,
retrospective ECG-gated helical acquisition often represents a good choice, but the
application of the tube-current modulation during the cardiac cycle to the retrospec-
tive ECG-gated helical acquisition is anyway recommended, in order to maintain
radiation exposure at reasonable level.
Chronic kidney disease can represent an important limitation to the exam in this
category of patients. However, dual energy acquisition offers the possibility to per-
form CCTA with very low dose of contrast agent.

Calcium Scoring
Calcium hydroxyapatite deposition in coronary arteries always occurs in the intima
associated with coronary atherosclerotic plaque formation; here, inflammation trig-
gers processes similar to osteogenesis. The majority of elderly patients presents
with coronary calcium without any symptoms. Non-contrast cardiac CT is used to
establish the coronary artery calcium score (CACS), also known as the Agatston
score, considering each calcified plaque using dedicated software. Finally, scores
for all detected lesions are summarized to obtain the total score. Non-contrast CT
should be ECG-gated and acquired at 120 kVp; however, recent studies documented
strong correlation with CACS measured from non ECG-gated non contrast CT scan
and also from ECG-gated low dose (80 kVp) scan [23].
In asymptomatic individuals the presence and the extent of coronary calcium
correlate to total atherosclerotic plaque burden and to the risk of future cardiovascu-
lar events [24]. Any coronary calcium, including a single focus of calcium, indicates
increased atherosclerotic cardiovascular disease risk over the next 10–15 years,
while its absence indicates less than 1% risk for atherosclerotic cardiovascular
events in the next 10 years [25, 26].

Plaques and Stenosis Assessment

CCTA can unravel both calcified and non-calcified plaques [27].
Moreover, CCTA can identify plaque at high risk of rupture [28]. CCTA features
of plaque vulnerability include positive remodelling, large plaque volume, low
attenuation, spotty calcification, and napkin ring sign. In the case of rupture, subse-
quent thrombus appears as a low-density material within the coronary lumen that
may completely occlude such lumen and is often associated with pronounced posi-
tive remodelling [29, 30].
114 A. Palmisano et al.

The use of Coronary Artery Disease Reporting and Data System (CAD-RADS)
[31] to report the results of a CCTA examination should be promoted to improve
standardization and communications among physicians.

Bypass Graft and Stent Assessment

CCTA has a pivotal role in the follow-up after stent implantation and coronary
artery bypass graft (CABG).
In-stent restenosis (ISR) is defined as a reduction >50% of the diameter of the
coronary artery lumen inside or at the edges of the implanted stent (Fig. 5.1).

a b c

Fig. 5.1 (a–d) CCTA of a 77-year-old man with previous PCI on left anterior descending artery
(a), circumflex (b) and right coronary artery (c). CCTA showed good patency of the coronary
artery stent on left anterior descending artery (a) and circumflex artery (b), without signs of neo-
intimal hyperplasia, differently from stents on the right coronary artery with evidence of intrastent
stenosis >50% in the proximal and medium stent and total occlusion of the distal stent
5 Heart Diseases in Geriatric Patients 115

a b c d

Fig. 5.2 (a–d) CCTA of a 78-year-old man with previous CABG: left internal mammary artery on
left anterior descending artery (arrow in a), and a venous graft for the posterior descending artery
(arrow in c). CCTA documented good patency of both grafts as showed in 3D volume rendering (a
and c) and multiplanar reconstruction (b and d)

Identifying in-stent stenosis by coronary CTA is problematic and prone to inaccu-

rate results, especially for stents with diameters <3.0 mm [32, 33].
CTA has excellent accuracy for the evaluation of coronary artery bypass grafts
[34–36] patency in the early (<1 month) as well as late (>1 month) postoperative
period (Fig. 5.2).

CT Tissue Characterization: Perfusion and Scar

CCTA alone is unable to accurately estimate the functional hemodynamic effect of a
coronary stenosis. Stress perfusion CT can offer non-invasive functional information,
which aids in selecting patients eligible for revascularization [37]. CT stress perfusion
evaluates the attenuation differences induced in the myocardium by the first pass of
the iodinated contrast material during pharmacological stress [38]. Stress can be
obtained using adenosine or dipyridamole or regadenoson, which induces maximum
vasodilation and steal effect [39]. Different protocols of CT stress perfusion are avail-
able. It can be performed in static or dynamic mode. Some centres prefer to acquire a
stress scan followed by rest, while others acquire the rest scan first. Perfusion defects
appear as a subendocardial or transmural hypoattenuating area in a coronary territory.
The dynamic acquisition can be used to perform quantitative analysis to evaluate the
myocardial blood flow (MBF) and the coronary flow reserve (CFR) that are used for
the evaluation of epicardial disease and microvascular dysfunction [39].
Many studies confirmed that CTA pooled with CT stress perfusion has a high
accuracy for predicting obstructive CAD (>50%) and has a high specificity and
positive predictive value (PPV) [37, 40, 41]. However, CTP is generally not the first
stress imaging test of choice, mainly because of the still very limited availability
since CTP requires additional resources, top-class scanner and advanced expertise
in using this technique and protocol.
Several studies showed the possibility to detect myocardial scar and quantify
myocardial ECV with a delayed scan acquired at 10 min after the administration of
116 A. Palmisano et al.

contrast media, with good accuracy compared to MRI [20–22]. Different scanning
protocol were tested based on low kV single energy scan or dual energy acquisition
[20–22].

5.2.3.2 MR Imaging

Cardiac Magnetic Resonance allows a complete morpho-functional and structural
characterization of the myocardium; however, it requires long acquisition time, lim-
iting its applicability in the emergency setting as well as in elderly patients with
limited capability of collaboration. Geriatric patients generally have limited compli-
ance because of the long exam time and difficulties to breath-hold. Therefore, faster
cardiac protocols are highly desirable, especially for patients in unstable conditions
or requiring acute care [42].
In the setting of ACS, cardiac MRI has a primary role when an advanced assess-
ment of potential complications is required [43, 44]. If performed early (i.e., during
the first 2 weeks after PCI), CMR with a standard protocol can accurately assess
ventricular function, myocardial oedema and myocardial injury, detect early myo-
cardial infarction complications [42] such as a free wall or interventricular septum
rupture and detect thrombus or differentiating between aneurysm and pseudoaneu-
rysm [45, 46]. Furthermore, it allows the depiction of other parameters such as
microvascular obstruction (MVO), intramyocardial haemorrhage, the area at risk
and the myocardial salvage index (MSI) [47] (Fig. 5.3). These biomarkers are
increasingly used in the clinical trials designed to assess the effectiveness of new
treatments in the setting of acute myocardial infarction.
T2 STIR imaging in at least two orthogonal planes is necessary to outline myo-
cardial oedema, which represents a nonspecific response of the myocardium that is
seen in patients with acute myocardial damage. It typically results in a hyperinten-
sity of the injured myocardial area, and it is also very useful to differentiate acute
from chronic myocardial infarction [48].
Cardiac LGE MRI has a primary role in the identification and quantification of
myocardial necrosis [49]. The ischemic LGE pattern refers to subendocardial
enhancement, with a variable transmural extent that follows a coronary artery terri-
tory distribution and allows the differential diagnosis with other pathologies that
present with a non-ischemic LGE pattern [50, 51]. LGE imaging can also easily
depict microvascular obstructions or intramyocardial haemorrhage, which are two
critical prognostic markers. Furthermore, new advanced software allows an accu-
rate automatic or semiautomatic quantification of scar burden, which is an essential
predictor of LV remodelling and consequently of prognosis [43, 44, 52, 53].
Recently introduced, T1 and T2 mappings consist in parametric quantitative
sequences that provide tissue-specific T1 and T2 values and allow an objective
assessment of myocardial abnormalities. In acute ischemia settings, T1 mapping
shows high native T1 and extracellular volumes of acutely infarcted and oedema-
tous myocardium, while T2 mapping can quantitatively evaluate oedema and iden-
tify intramyocardial haemorrhage or MVO [54, 55].
In elderly patients, cardiac MRI can be useful late after PCI (i.e., within 1 month),
especially in patients with anterior infarction, previous infarction or heart failure
5 Heart Diseases in Geriatric Patients 117

a b

c d

Fig. 5.3 (a–d) CMR images of a 45-year-old man with STEMI. CMR images were performed
6 days after STEMI due to culprit lesion on left circumflex artery, promptly treated with PCI. CMR
showed oedema on the lateral mid-basal wall (a and c) involving 34% of myocardial mass associ-
ated with transmural post-ischemic LGE (b and d) involving 23% of myocardial mass. Endocardial
hypointensity was recognizable in the endocardium of the injured myocardium both on STIR
images (asterisks in a and c) and LGE images (asterisks in b and d) referrable to myocardial haem-
orrhage and microvascular obstruction respectively

[43, 56]. In this setting, imaging is indicated for the assessment of the LV ejection
fraction before hospital discharge [47, 56] especially when echocardiography is
suboptimal or inconclusive [47, 57].
Moreover, CMR represents a game-changer in all the cases of cTnT elevation of
unknown origin, outlining the diagnosis of all the conditions that can mimic AMI,
such as Takotsubo cardiomyopathy, myocarditis, and MINOCA. CMR is an impor-
tant management tool in this setting since it has a crucial role in guiding therapy
[42, 58].
In patients with chornic coronary syndrome with intermediate stenosis [59, 60],
stress cardiac MRI is an effective imaging to identify myocardial ischemia and via-
bility, resulting fundamental for guiding patients’ revascularization. Inducible isch-
emia is detected as an area of myocardial hypointensity in a coronary territory,
extending from the endocardium to the epicardium, recognizable during the first
pass perfusion at the peak of myocardial enhancement, not visible at rest perfusion
and in the absence of scar at LGE.
118 A. Palmisano et al.

5.3 Heart Failure

5.3.1 Introduction

Heart failure (HF) is a clinical syndrome characterized by typical symptoms (e.g.,

dyspnoea, fatigue) and signs (e.g., peripheral oedema, jugular engorgement) due to a
structural or functional cardiac anomalies which lead to a reduction of the stroke
volume or an increase of the filling pressure. In this condition, the heart cannot guar-
antee an adequate volume of blood and oxygen to tissues [61]. Nowadays, around
23 million people are affected by HF worldwide, and these numbers are increasing.
The majority of these patients are more than 70 years old, with men affected more
than women, with an overall HF prevalence of ≥10%. Furthermore, HF is frequently
underdiagnosed in this group of patients because of the lack of specific symptoms
and the concomitant presence of many comorbidities that can lead to misdagnosis [1].

5.3.2 Aetiology and Pathophysiology of Heart Failure

Heart failure represents the latest stage of every cardiovascular disease. It is defined
as ischemic heart failure if it is a consequence of CAD or as non-ischemic heart
failure if it is due to other diseases (e.g., hypertension, idiopathic cardiomyopathies,
valvular diseases, inflammation, auto-immune diseases, nutritional deficiency,
infections, and drugs). These conditions can trigger two primary pathophysiological
alterations: volume (i.e., valvular regurgitation) or pressure overload (i.e., hyperten-
sion, aortic stenosis) and systolic dysfunction (i.e., CAD, idiopathic cardiomyopa-
thies) [62].
Clinically, it can manifest as left HF, whose symptoms are mainly due to low
cardiac output with fatigue and syncope or pulmonary congestion with dyspnoea
and pulmonary oedema. Instead, jugular vein engorgement, hepatic congestion, and
peripheric oedema are the typical signs of right HF [63].
EF is an essential parameter in patients affected by HF, and European guidelines
use EF to classify HF in three different categories: HF with preserved ejection frac-
tion (HFpEF, >50%), HF with mid-range reduction of EF (HFmrEF, 40–49%), and
HF with reduced ejection fraction (HFrEF, <40%). This classification is of para-
mount importance because it reflects aetiologies and comorbidities of HF, with an
important impact on prognosis and therapy [61].
This classification also reflects the pathophysiological mechanism of HF, which
can be distinguished in systolic and diastolic HF. In systolic dysfunction, there is a
contractile insufficiency of the left ventricle that loses its capability to guarantee an
expected cardiac output, leading to HFrEF (i.e., CAD, DCM) [61]. Dilated
Cardiomyopathy (DCM) is a form of HFrEF and is defined as a left ventricular dila-
tion and systolic dysfunction in the absence of coronary artery disease or abnormal
loading conditions proportionate to the degree of LV impairment. It can be due to
many causes, such as alcohol consumption, genetic aetiology (e.g., lamin A/C muta-
tion or myotonic dystrophy), anthracycline therapy history, HIV infection,
5 Heart Diseases in Geriatric Patients 119

persistent tachyarrhythmia (>100 beats/min), and inflammatory disease (e.g., sar-

coidosis, giant cell myocarditis, or Lyme disease) [64].
In diastolic dysfunction, the left ventricle generally appears thickened, with a
normal cavity but reduced left ventricular compliance, leading to abnormally
increased filling pressures, which leads to a HFpEF. Even if counterintuitive, this
form of HF appears to be very common in the elderly population [65]. Besides
assessing EF, cardiac imaging can outline the pathological process of diastolic dys-
function generally caused by hypertensive cardiopathy, pericardial constriction,
aortic stenosis and some infiltrative disorders, among which amyloidosis represents
a significant cause in the geriatric population [66].

5.3.3 Multimodality Imaging with a Particular Focus

on CT and MRI

Diagnosis of HF is typically based on clinical signs and symptoms, with echocar-

diography that represents a primary tool [61]. For the differential diagnosis between
HFrEF and HFpEF, EF evaluation is obtained via TTE, and when it is suboptimal or
inconclusive, CMR can be the exam of choice. As such, imaging plays a pivotal role
in the diagnosis and the identification of HF aetiology [67]. Ischemia is the primary
cause of HF and can be diagnosed through anatomical techniques such as CCTA or
ICA, or with functional techniques such as stress echo and CMR, or nuclear medi-
cine techniques [68].
Chest radiography is one of the first exams needed to study a patient with sus-
pected HF in ED, mainly to exclude other causes of dyspnoea. Furthermore, it rep-
resents a straightforward methodology to monitor the response to therapy in acute
settings.
Echocardiography is the pivotal technique for patients with HF of unknown ori-
gin. It can help to establish the aetiology and severity of HF as it can provide cham-
ber dimensions, biventricular function, valvular diseases, and systolic/diastolic
function (i.e., filling pressures and patterns). Given its ability to establish the EF
value, echocardiography is the primary tool to diagnose a HF with preserved or
reduced EF, providing preliminary insights into the diagnosis. Regional wall motion
abnormalities may suggest an ischemic aetiology, while a homogeneous dilatation
with diffuse motion abnormalities may be typical of a non-ischemic disease which
can show other characteristic findings [61, 68].

5.3.3.1 CT Imaging

CCTA is a valuable tool for evaluating the coronary arteries, and it is primarily used
to exclude CAD as a possible cause of HF of unknown origin. CTCA has been pro-
posed as a gatekeeper to ICA for patients with new-onset HF [69]. Furthermore,
many authors suggest that in these patients calcium score with an Agatston score of
0 has been shown to have a 100% sensitivity to exclude “high-risk CAD”, defined
as left main coronary artery stenosis or stenosis in at least two major epicardial
coronary arteries [70–72]. Thanks to the increase in temporal resolution of CT
120 A. Palmisano et al.

scanner in the recent years, CCTA can accurately evaluate cardiac structure and
function. Moreover, using Late Contrast Enhancement (LCE) scan, CT could also
identify non-ischemic cardiac disease underlying HF and may provide a quantifica-
tion of myocardial stiffness through the measurement of ECV with results compa-
rable to CMR [73, 74].

5.3.3.2 MR Imaging

MR is the gold standard for volumetric analysis and cardiac function assessment,
thanks to its high accuracy and reproducibility. Cine imaging can assess the severity
and regionality of left ventricular dysfunction, volumes, and wall thickness.
Moreover, it can evaluate myocardial perfusion, viability, and fibrosis, which can
aid the evaluation of the aetiology of new-onset HF [75]. Recently introduced para-
metric techniques such as T1/T2 mapping and ECV can easily detect diffuse fibrosis
earlier than older LGE sequences [76]. However, LGE imaging is the primary
sequence for differentiation between ischemic and non-ischemic cardiomyopathies,
based on the pattern, location and distribution of LGE. Ischemic pattern will always
involve the subendocardium, whereas a non-ischemic pattern will always be limited
to the mid- or epicardial wall sparing the subendocaridum [50, 77]. The absence of
LGE in patients with a severe reduction of EF suggests non-ischemic cardiomyopa-
thies such as idiopathic dilated, inflammatory, alcoholic, Takotsubo, and peripartum
cardiomyopathies [78].

5.3.3.3 Indications and Planning for ICD and ICD-CRT

Cardiac imaging is also particularly useful to establish if and when devices such as
implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy
(CRT) have to be implanted [79].
ICD represents the primary therapy to prevent sudden cardiac death in patients
with EF <35%. Implant choice mainly depends on EF evaluation. When EF is lower
than 35%, patients with HFrEF need to be implanted [80]. EF evaluation is mainly
achieved through echocardiography, while CMR is indicated only if US is subopti-
mal or inconclusive. However, some authors suggest that echocardiography seems
to overestimate EF in HFrEF patients, missing patients potentially eligible for ICD
therapy. Moreover, many studies suggest that EF alone is insufficient to assess the
risk of sudden cardiac death in HF patients. The integration of LGE CMR imaging
can assess the presence, the distribution and the burden of myocardial scars, which
represent the important risk-modifiers for the evaluation of defibrillator placement
[79, 81]. For this reasons, CMR should always be applied in borderline cases.
CRT is a fundamental therapy for patients with refractory HF. Many studies have
demonstrated that CRT can improve cardiac survival, decrease recurrent HF hospi-
talization and ameliorate the overall quality of life. Patients with specific character-
istics such as wider QRS, left bundle branch block, female sex and non-­ischemic
cardiomyopathy are those who benefit the most from CRT [82]. A key factor seems
to be ventricular dyssynchrony, which can be assessed via echocardiography
through M mode, pulsed-wave Doppler imaging, tissue Doppler imaging (TDI),
5 Heart Diseases in Geriatric Patients 121

speckle tracking, and real-time three-dimensional (RT3D) imaging [83].

Nevertheless, an important trial (PROSPECT) established that none of the many
echocardiographic modalities is sensitive enough to be helpful in estimating
response to CRT in clinical practice [84].
CMR can qualitatively or quantitatively assess interventricular and intraventricu-
lar dyssynchrony with different modalities such as myocardial tagging, strain-­
encoded MRI (SENC), phase-contrast MRI, and displacement encoding with
stimulated echoes (DENSE). As for echocardiography, all these modalities have not
yet proved to be useful.
On the other hand, the assessment of LGE at CMR imaging can provide valuable
information in the prediction of response to CRT therapy [83] and may also help in
improving the results of CRT therapy guiding the electrode implantation. LGE can
evaluate three fundamental features that can predict a lower response to CRT:

1. The extent of the scar: if it is <15%, LGE can predict a good response to
CRT [85].
2. The location of the myocardial scar: if it involves the postero-lateral wall, the
myocardial scar is predictive of a lower response.
3. The presence of fibrosis in the site of LV lead placement, which may reduce the
effectiveness of CRT [86].

Furthermore, some authors discovered that pacing in a site with <50% scar trans-
murality was associated with response to CRT [87].
In conclusion, CMR can provide a complete cardiac assessment for CRT, since it
is the gold standard to evaluate the size and the function of the chambers, determine
prognosis, and provide invaluable information about the probability of response to
CRT via LGE.

5.3.4 Amyloidosis

As stated above, a common cause of HF in the elderly population is HFpEF. Imaging

techniques are of fundamental importance not only for evaluating the EF, which is
essential for the diagnosis, but also for the characterization of the pathological pro-
cess that causes the underlying diastolic dysfunction.
Amyloidosis is a systemic infiltrative disease due to the presence of proteins with
unstable structures that form aggregates and amyloid fibrils which can deposit in
many different tissues. Immunoglobulin light chains (AL amyloidosis) and amyloid
transthyretin (ATTR amyloidosis, hereditary, or wild type) are the most frequent
variants determining cardiac amyloidosis (CA) and represent two CA subtypes with
completely different prognosis and management [88]. The true prevalence of ATTR
wild-type is unknown; autopsy studies revealed that 25% of the hearts of people
aged 80 years or older contained wild-type fibrils regardless of the presence of
symptoms [89].
122 A. Palmisano et al.

The high accessibility and the ability to describe both cardiac structure and func-
tion make echocardiography the first-line tool in CA assessment. The typical echo-
cardiographic findings in CA comprise a small left ventricle with concentric
hypertrophy, a sparkling myocardial appearance, a biatrial enlargement with an
increased atrial septum thickness, and a restrictive physiology [90].
Recent ultrasound techniques such as speckle tracking echocardiography were
more sensitive than traditional echocardiography in detecting global and regional
cardiac function changes. Several groups have shown the good sensitivity and speci-
ficity of basal to apical longitudinal strain ratio for differentiating CA from other
cardiac pathologies [91, 92].
CMR is the imaging tool of choice to diagnose CA because of its tissue charac-
terization capabilities [93]. LGE is historically the cornerstone of CMR to diag-
nose CA in patients whose kidney function allows contrast medium administration.
The typical LGE pattern in CA is represented by diffuse and inhomogeneous myo-
cardial hyperenhancement; sometimes, subendocardial circumferential hyperen-
hancement can be present in some patients while others can also show transmural
hyperenhancement [94]. Some researchers suppose that these different LGE pat-
terns are representative of different phases due to continuous amyloid deposition,
with progression from no LGE to transmural LGE [95]. Another typical sign of
amyloid deposition is the abnormal myocardial and blood-pool kinetics demon-
strated in the inversion time scout sequence [96]. Native myocardial T1 mapping
enables CA diagnosis without the need to administer gadolinium since very high
T1 values are a typical feature of CA [97]. The integration of native T1 with post-
contrast T1 values allows a non-invasive quantification of ECV [97]. High value of
T1 mapping and ECV represent one of the earliest imaging signs for cardiac amy-
loid deposition (Fig. 5.4); they can be altered even when LGE is absent [98].
Instead, T2 mapping can show oedema in both types of amyloidosis, but this is
generally larger in light chain CA [93]. While the integrated use of clinical find-
ings, electrocardiography, echocardiography, and CMR makes the diagnosis of
cardiac amyloidosis possible, these methodologies cannot accurately contribute to
the characterization of the type of the underlying amyloid deposition. Myocardial
scintigraphy with bone avid tracers has high sensitivity and specificity to diagnose
ATTR CA; the ease of access, imaging simplicity, low cost and high specificity for
ATTR CA are some of the advantages of this diagnostic tool [99–101]. In conclu-
sion, cardiac imaging represents a critical tool for the diagnosis of CA. The step-
wise use of various imaging modalities in conjunction with the clinical and
laboratory data diagnose this pathology in most patients; therefore, cardiac biopsy,
the gold standard diagnostic test to confirm and provide typization of amyloidosis,
is no longer routinely performed in clinical practice due to its invasive nature and
limited availability.
5 Heart Diseases in Geriatric Patients 123

a b c

d e f

Fig. 5.4 CMR images of a 73-years-old man with cardiac amyloid. Cine SSFP image (a) shows a
concentric myocardial hypertrophy (end-diastolic wall thickness of mid-basal septum: 19 mm;
end-diastolic mass: 147 g) with slight diffuse edema (global T2 mapping: 58 ms; normal value <50
ms) and marked increase of native T1 mapping (b–c) with global T1: 1220 ms (normal value<
1045 ms) and of ECV values (e, f) with global ECV of 42% (normal value <27%) suggestive of a
huge expansion of the extracellular space. LGE showed endocardial hyperitensity with a gradient
from the bases to the apex (d). CMR findings were suggestive for cardiac amyloid

5.4 Valvular Heart Diseases

Valvular heart disease (VHD) increases in incidence at increasing age. Changing

societal demographics with an ageing population, advances in imaging and the
explosion of transcatheter interventional techniques have revolutionized the land-
scape of clinical management of these diseases. Multimodality imaging is essential
in VHD for establishing diagnosis, monitoring disease, planning interventional and
surgical procedures and follow-up.

5.4.1 Aortic Stenosis

5.4.1.1 Aetiology and Pathology

Aortic valve stenosis (AS) is the primary valve disease with the highest prevalence
in western countries [102]; age-related degenerative calcific AS is now the most
common aetiology of AS, followed by rheumatic stenosis and congenital stenosis
[103]. Calcific AS is an active and progressive disease that shares similarities with
atherosclerotic diseases such as inflammation, lipid infiltration and calcifica-
tion [104].
124 A. Palmisano et al.

5.4.1.2 Pathophysiology
A normal aortic valve has an opening area between 3 and 4 cm2; a progressive
reduction of the aortic valve area leads to a significant obstruction to the transvalvu-
lar flow and results in a transvalvular gradient. These haemodynamic changes cause
an increase in pressure afterload and ventricular wall stress that stimulates hypertro-
phy of the left ventricular myocardium [105, 106]. In the early stages of the disease,
left ventricular hypertrophy (LVH) reduces parietal stress and preserves the systolic
function of the left ventricle; over time, LVH can be maladaptive with literature
evidence that the hypertrophic myocardium represents an adverse prognostic marker
in various clinical conditions [107–109]. LVH in patients with aortic valve stenosis
is highly heterogeneous and is only weakly correlated with the extent of valve
obstruction; it is more closely associated with age, male sex and obesity [110–115].
The heterogeneity of the myocardial response in terms of LVH has critical prognos-
tic implications; it has been shown that with the same valvular obstruction, the find-
ing of an inappropriate left ventricular mass significantly increases the mortality of
patients with AS aortic [116]. The negative prognostic impact of an inappropriate
left ventricular mass can be related to an increase in myocyte apoptosis and intersti-
tial myocardial fibrosis deposition [117–119].

5.4.1.3 Multimodality Imaging

Echocadiography is the first-choice imaging technique to evaluate patients with AS
and allows an accurate assessment of the severity of valvulopathy and of the systolic
function of the left ventricle [120], in most of patients. Furthermore, by integrating
the values of the valvular area, of the transvalvular gradient, and the left ventricle
ejection fraction, it is possible to identify different phenotypes of AS with echocar-
diography. Such phenotypes are normal flow-high gradient, low-flow-low-gradient,
paradoxical low flow-low gradient [120].

CT Imaging
CT with its high spatial resolution images of the aortic annuls and root represents a
central modality for planning of transcatheter procedure of aortic valve replacement
(TAVR/TAVI). In TAVI candidates, CT imaging provides a comprehensive assess-
ment, including the analysis of the aortic annulus, the characterization of the valve
anatomy (bicuspid or tricuspid), the burden of the aortic valve and aortic root calci-
fication, and the evaluation of the peripheral vascular accesses [121, 122] (Fig. 5.5).
The evaluation of aortic valve calcifications by CT has been proposed to estimate
the severity of AS when the echocardiographic parameters are discordant: the cut-­
off value of AV calcifications associated with severe AS is ≥1274 AU in women and
≥2065 AU in men [123]. The evaluation of the aortic annulus anatomy is of para-
mount importance for a successful TAVI outcome. The annulus diameter dictates
the aortic prosthetic size, making this measurement a critical point for procedural
success; any error at this level could result in serious complications [124–126]. The
aortic annulus has an oval shape with long and short diameters; CT is exceptionally
accurate to obtain these measurements, as well as the perimeter and the area of the
aortic annulus [127]. Another critical parameter determining the success of TAVI is
5 Heart Diseases in Geriatric Patients 125

a b e

Fig. 5.5 CT angiography for planning of transcatheter aortic valve replacement in a 70-years-old
woman. CT images shows a fibrocalcific degeneration of the aortic valve (a), with tricuspid mor-
phology and moderate calcifications, characterized by severe stenosis with aortic valve planimetric
area equal to 0.7 cm2 (yellow area in b). CT images was used to characterize landing zone (multi-
planar and 3D reconstruction of the aortic root in c and d respectively) and pheriperal accesses (e)

the height of the coronary ostia from the annulus plane, since the prosthetic valve or
the native valve cusps displaced by the TAVI procedure, may cause coronary ostium
obstruction and may impede the coronary ostial flow [128]. The recommended
annulus-ostia length is >10–11 mm for the Edwards-Sapien valve, while there is no
recommendation for Core Valve [128].

CMR Imaging
Cardiac magnetic resonance (CMR) is not routinely used in the diagnostic work-
flow of AS; the main reason for this is that AS traditionally has been considered as
a disease of the valve while the myocardium has been largely ignored. On the
contrary, recent studies documented a progressive myocardial remodelling in AS
126 A. Palmisano et al.

from myocyte hypertrophy to increase of myocardial fibrosis till an irreversible

stage. The identification of different stages of myocardial remodelling is of pivotal
importance potentially impacting on the treatment success. CMR represents the
standard of reference for the non-invasive evaluation of myocardial fibrosis. LGE
CMR is the most accurate modality to visualize focal midwall myocardial fibrosis,
which was found in up to 38% of patients with moderate or severe AS aortic and
has been associated with an increase in mortality [129]. However, LGE is able to
detect only replacement dense fibrosis, which is irreversible and associated with
advanced stages of remodelling [130], differently from interstitial fibrosis which is
reversible. The more recently introduced T1 mapping technique can quantify inter-
stitial fibrosis throughout the measurement of the extracellular volume fraction
(ECV), improving myocardial characterization also at the earliest stages [131].
ECV showed an excellent correlation with fibrosis at histology, and its alteration
correlates with a symptomatic status [131–133]. In the future the assessment of the
interstitial fibrosis could find a role in guiding the timing of AS interventional
treatment.

5.4.2 Mitral Regurgitation

5.4.2.1 Introduction
Mitral regurgitation is the second most frequent valvular heart disease in western
world [103]. Surgery is the first-choice in symptomatic patients with severe MR
[120]; however, surgery is often denied to elderly patients because of their comor-
bidities [134]. The denial of surgical treatment to elderly patients with significant
MR contributed to the tumultuous spread of percutaneous techniques in treating this
pathology [135] with imaging playing a pivotal role in procedural planning and
guiding.

5.4.2.2 Aetiology and Pathophysiology

MR could be primary or secondary based on the underlying pathophysiology with
impact on therapy [120]. Secondary or functional MR is the most frequent form in
the elderly population since it is commonly seen in patients with ischaemic and
idiopathic cardiomyopathies. In secondary MR, the leaflets and chordae have a nor-
mal structure, and the regurgitation is due to an imbalance between closing and
tethering forces on the valve which are consequences of alterations of left ventricle
shape [136]. In primary MR, one or more elements of the mitral valve apparatus are
directly affected, and the most frequent aetiology is degenerative, characterized pri-
marily by mitral valve prolapse [137].

5.4.2.3 Multimodality Imaging

Echocardiography is the crucial examination in detecting MR [120]; it grades MR
severity, establishes mechanism and aetiology, and provides a complete evaluation
both of left ventricular systolic function and the degree of left atrium dilatation.
5 Heart Diseases in Geriatric Patients 127

Furthermore, it quantifies pulmonary pressure and describes associated valve

lesions. Transoesophageal echocardiography (TOE) provides a comprehensive
description of the mitral valve, and it should always be performed when transtho-
racic echocardiography is inconclusive; furthermore, TOE is essential for guiding
procedures in transcatheter valve interventions [138].
Echocardiographic assessment of the severity of mitral regurgitation can be qual-
itative, semiquantitative or quantitative; however, since no single parameter has
proved to be more reliable than others, the evaluation is generally multi-parametric,
mainly qualitative, although a quantitative approach is recommended when possi-
ble [139].
Quantitative severe MR is defined when the regurgitant volume is >60 mL, and
the regurgitant fraction is around 50%, with an orifice area of >0.4 cm2.
Echocardiography plays a fundamental role in the selection of candidates for surgi-
cal treatment that generally happens when the patient affected by MR is symptom-
atic or asymptomatic but has less than 60% EF or a left ventricular end-systolic
diameter (LVESD) >45 mm, or he is also affected by atrial fibrillation or pulmonary
hypertension [120].

CT Imaging
Transcatheter mitral valve repair should be performed when the heart team evalu-
ates a high surgical risk for the patient. In functional MR, TMVR is indicated in
patients with severe MR where medical therapy and cardiac resynchronization ther-
apy (CRT) are not effective [140]. In primary MR, TMVR is indicated in the pres-
ence of comorbidities such as CKD, COPB, advance age, and severe impairment of
left ventricular function.
Two main transcatheter mitral valve repair strategies for severe MR include
edge-to-edge repair (MitraClip) and annuloplasty rings (Cardioband) [141–143].
MitraClip is the selected treatment of moderate to severe degenerative and func-
tional MR, while the Cardioband system consists of a percutaneous annuloplasty
that can be used in settings of functional MR resulting from systolic dysfunction or
annular dilatation. As mentioned above, echocardiography is an initial tool to assess
mitral valve structure and disease; however, this can be challenging in patients with
limited acoustic windows also considering the complexity of the mitral valve appa-
ratus. In these cases, CCTA allows a full cardiac cycle acquisition, outlining similar
morphologic findings to echocardiography and MRI such as mitral annulus geom-
etry, dimensions and calcifications, morphology and mobility of valve and sub-­
valve apparatus, with an improved spatial resolution. It can also be used to assess
the anatomy of coronary arteries and of the aortic valve and interatrial septum, but
it cannot assess the flow that can only be analysed via echocardiography or MRI
[144, 145]. Furthermore, CTCA can easily exclude the presence of an atrial throm-
bus which would represent a contraindication to percutaneous mitral valve repair.
Critical anatomic selection criteria for MitraClip device in functional MR are
Coaptation length (≥2 mm), and depth (<11 mm). In contrast, Flail gap (<10 mm)
and width (<15 mm) are the ones fundamental for MitraClip in primary MR
128 A. Palmisano et al.

(prolapse) [146]. For Cardioband implantation, which is a percutaneous annuloplas-

try, CT planning must assess the location of the transeptal puncture and the relation-
ship between left circumflex coronary artery anatomy [143].

MR Imaging
Even if echocardiography represents the main tool for diagnosis and follow-up of
MR, MRI remains the gold standard for comprehensive assessment of the pathology
and has shown higher accuracy than echocardiography to evaluate MR severity and
guiding surgery. Phase contrast sequences can directly or indirectly quantify MR
severity [147]. Tissue characterization with LGE and mapping may also help in the
identification of the aetiology of secondary MRI and may provide information about
myocardial remodelling.

5.5 Conclusion

Increase in life expectancy will lead to increased incidence of age-related cardiovas-

cular disease.
Cardiovascular imaging has a fundamental role in the diagnosis, risk stratifica-
tion, planning of treatment and monitoring of cardiac disease evolution in geriatric
patients. However, imaging in elderly may be a challenge for reduced patient com-
pliance and comorbidities. Recent advancement in technology allows an optimiza-
tion of acquisition protocol with faster acquisition time and limited dose of contrast
agent. However, more efforts and data are necessary to develop standardized proto-
cols and to draw up guidelines and appropriate criteria for such specific population.

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Vascular Diseases in Geriatric Patients
6
Gloria Caredda, Giuseppe Guglielmi, and Luca Saba

6.1 Introduction

Over time, the mean age of the population has progressively increased, with a large
number of geriatric subjects. It is predicted that in 2030 they will represent the 19%
of the general community in the USA, with about 19 millions of people over
85 years of age, with an increase of 22% of the geriatric population in 2050 and of
32% in 2100.
In this scenario, there has been a parallel increase in the number of the age-­
related diseases, thus it is possible to consider the presence of a concrete “demo-
graphic transition.” In particular, the geriatric syndromes play a fundamental role,
and they are generally related to a vascular chronic disease. More in depth, about
40 millions of people over 65 years of age are affected by a cardiovascular disease,
which, together with other cerebrovascular conditions, represents the main cause of
death in this age range, constituting an important healthcare, economic, and
social issue.
Such a relative matter leads to the necessity of developing new prevention and
treatment strategies, considering the vascular diseases at the base of a syndromic
process, which might require a different patient management with respect to the
single disease affecting a healthy subject. This is important, in particular, for the
female patients, because, with aging and the hormone physiological changes, these
diseases often occur with an insidious onset.
Generally, the aging process of the cardiovascular system is characterized by a
stiffening of the vascular walls and the occurrence of atherosclerosis, affecting both
the large vessels and the microvasculature, leading to organic systemic alterations.

G. Caredda · L. Saba (*)

Department of Radiology, University of Cagliari, Cagliari, Italy
G. Guglielmi
Clinical and Experimental Medicine, University of Foggia, Foggia, Foggia, Italy
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 137
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_6
138 G. Caredda et al.

The main risk factors related to vessel aging, which lead to vasculature system
diseases, are represented by patient aging, smoking, other conditions such as diabe-
tes mellitus, hypertension, hyperlipidemia, and other factors (some of them non-
modifiable) like race, ethnicity (with an increased risk in African American and
Hispanic subjects), chronic kidney disease, metabolic syndrome, high levels of
C-reactive protein, β2-microglobulin, cystatin C, lipoprotein, and homocysteine.
Among these factors, the main modifiable one is smoking, which increases the risk
of peripheric vascular disease by about four times, with an onset that precedes by
10 years than that in non-smokers. Moreover, smoking patients usually have a worse
prognosis.
Aside from these conditions, in geriatric patients, vascular trauma plays a key
role. Their incidence is lower if compared to their young counterpart, but, at the
same time, they are more severe. Indeed, in this age range, the mortality for vascular
trauma (40% for falls) is higher than that of non-geriatric adults and, with respect to
young people, death is more frequent in the emergency departments. The main
cause is represented by car accidents, followed by falls (with an incidence of 32%
in subjects over 75 years of age), with a predominance of abdominal and upper
limbs harms, more frequent than in non-geriatric adults.
This is related to the physiological processes of this age range, with alterations
affecting the nervous and the muscle-skeletal systems, which involve balance, mak-
ing these patients more susceptible to falls. Furthermore, if multiple diseases are
present, trauma management is more challenging, thus determining high morbidity
and mortality [1–3].

6.2 Physiological Vascular Changes in Geriatric Population

In the geriatric population, some aging-related changes show an impact in the car-
diovascular system, both as microscopic and as macroscopic alterations, leading to
several organic diseases. In particular, the oxidative stress, caused by high levels of
reactive oxygen species (ROS), has a crucial role in vasculature aging, reducing the
production of the endothelium-derived nitric oxide (NO), thus leading to vascular
stiffening, low parietal elasticity, and reduced tissue perfusion. Even aged dysfunc-
tional mitochondria contribute to the production of ROS. Moreover, while in young
subjects the result of ROS activity induces the activation of an antioxidant pathway,
characterized by the production of Nrf2, the aging-related changes inactivate this
process, making vasculature more sensible to ROS activity and more prone to
inflammation, with an increase of endothelial apoptosis. This is also due to proin-
flammatory changes in gene expression in the endothelial and smooth muscle cells,
which contribute to induce several conditions, from atherogenesis to microvascula-
ture diseases and aneurysm formation, by promoting the production of proinflam-
matory cytokines, determining the “senescence-associated secretory phenotype.”
Furthermore, senescent endothelial cells show a reduced angiogenetic and repara-
tive ability.
6 Vascular Diseases in Geriatric Patients 139

Finally, other processes contribute to vasculature aging, in particular alterations

in the balance between production and degradation of proteins, epigenetic modifica-
tions, and changes in the extracellular matrix, with a decreased vascular wall stabil-
ity [3–5].

6.2.1 Peripheral Artery Disease

The expression “peripheral artery disease” (PAD) includes the conditions involving
the arteries aside from the cranial and the cardiac territories. About 200 million
people in the world are affected by PAD, with a similar prevalence between men and
postmenopausal women. More frequently it is caused by atherosclerosis, which is
considered the most important determinant, but it can be due to diabetes mellitus,
smoking [6], vasculitis and other noninflammatory arteriopathies as well. This con-
dition is usually combined with coronary artery disease (CAD) and cerebrovascular
disease (CVD). An association between the lower extremity, the carotid, and the
renal arterial territory disease is frequent as well [7].
Two forms of PAD can be distinguished, the proximal one, which affects the
aortoiliac and the femoropopliteal tracts, and the distal subtype, involving the ter-
ritories distal to the popliteal arteries. In some patients, the latter type is character-
ized by a calcification of the middle layer of the wall, leading to a poorly compressible
vessel and a high mortality (Practice 2016).

6.3 Clinical Features

The most peculiar symptom is claudication, characterized by pain or cramps in the

lower limb caused by moderate exercise, which is alleviated with rest [6].
In some patients, acute or chronic critical ischemia of the limb may also be
observed, with pain in a rest state and ulcerations/gangrene in the distal region of
the foot. Other patients may be asymptomatic as well (Practice 2016).

6.4 Clinical Diagnosis

PAD can be assessed by estimating the segmental blood pressure in different levels
of the limb and evaluating the ankle-brachial index, the ratio between the systolic
blood pressure measured in the ankle and the systolic blood pressure assessed in the
arm, measured after 5–10 min of rest in a supine position [8]. The normal and patho-
logic values are reported in Table 6.1. In subjects with non-compressible arteries,
instead, the toe-brachial index might be assessed. Even exercise testing may be
valuable, using a treadmill or measuring the maximum walking times without
symptoms. Finally, in cases of critical leg ischemia, the evaluation of transcutane-
ous oximetry provides the clinician with important information (Practice 2016).
140 G. Caredda et al.

Table 6.1 Ankle-brachial index (ABI)

ABI value Indication

1.00–1.40 Normal
0.91–0.99 Borderline
<0.90 PAD
>1.40 Non-compressible arteries
PAD peripheral artery disease [8]

6.5 Imaging

6.5.1 Doppler Ultrasonography

The first-line technique for PAD evaluation is ultrasonography (US) with Doppler
imaging. It is a noninvasive and highly available tool, able to assess the atheroscle-
rotic plaque and monitor the patency of the revascularized vessels (Practice 2016).
The typical flow pattern of arterial vessels is triphasic, due to the high resistance of
muscle territory irroration, but it is lost in case of exercise or ischemia [9]. The
severity of the disease varies according to the grade of stenosis and to the value of
peak systolic velocity (PSV) and velocity ratio (VR), which are summarized in
Table 6.2. In particular, a stenosis of 50–99% is hemodynamically significant when
the PSV at the level of the lesion is double than that measured in a proximal arterial
segment (>200 cm/s with turbulence) [9] (Трансплантати 2017).
In particular, Doppler US (DUS) is the first-line imaging technique for the
assessment of the carotid territories, being able to distinguish patients with a high
risk for ipsilateral ischemic stroke and identify those subjects who are candidate for
endarterectomy or, on the other hand, for the only best medical treatment [8]
(Fig. 6.1).

6.5.2 Computed Tomography Angiography

Computed tomography (CT) angiography has the advantage of providing, in a rela-

tively short scanning time, high-resolution images which can be analyzed with the
postprocessing three-dimensional reconstructions, including the multiplanar recon-
struction (MPR), the maximum-intensity projections (MIP), the volume-rendering
technique and the curved multiplanar reconstruction, providing information about
the vessel stenosis and the plaques, and calcification of the arterial walls. On the
other hand, it might furnish insufficient information about heavily calcified or very
small vessels, not to mention the need for contrast agent administration, which
might not be suitable for some patients. In addition, according to the cardiac output
of the patient and considering the amount of time necessary for the contrasted blood
to flow from the injection site to the peripheral arteries, a different acquisition and
injection protocol should be adopted [10] (Practice 2016) (Figs. 6.2 and 6.3).
6 Vascular Diseases in Geriatric Patients 141

Table 6.2 Stenosis severity according to the degree of stenosis

Degree of arterial stenosis Percentage of stenosis PSV (cm/s) VR
Normal 0% <150 1.5:1
Stenosis 1–49% 150–200 1.5–2:1
Stenosis 50–99% >200 >4:1
Complete occlusion 100% – –
PSV peak systolic velocity, VR velocity ratio [9] (Трансплантати 2017)

a b

Fig. 6.1 (a–c) A 75-year-old male patient with left stroke. The MRI TOF shows the stenosis of
70% NASCET at the origin of the ICA (white open arrow). The FAT SAT MPRAGE shows the
presence of hyperintese signal in the plaque due to the presence of IPH

a b

Fig. 6.2 (a, b) A 78-year-old male patient with right stroke. The CTA shows in the right ICA the
presence of plaque in the ICA characterized by hypodense components and positive rim sign
(white arrows)
142 G. Caredda et al.

a b

Fig. 6.3 (a, b) A 84-year-old female patient. The CTA shows bilateral calcified plaque

CT angiography is also the first-line method for the evaluation of patients with
acute mesenteric ischemia and renal artery disease, providing a map of the arterial
vessels and demonstrating the presence of vascular thrombi [8].

6.5.3 Magnetic Resonance Angiography

Besides, another important tool is magnetic resonance (MR) angiography. Although

it cannot be performed in patients with metallic and non-MR safe devices, it pro-
vides information about large vascular territories without the use of radiations
(Practice 2016).
MR angiography can be performed without the use of contrast agents, for
instance with the acquisition of sequences such as time of flight (TOF), phase con-
trast, 3D half-Fourier fast spin echo (3D-FSE), balanced steady state free proces-
sion (b-SSFP), and quiescent-interval single-shot (QISS), providing information
about arterial stenosis and wall plaque avoiding the risk of complications such as
allergies or nephrogenic fibrosis. The acquisition of other sequences requires con-
trast administration, and it usually is the most frequently performed technique [11].

6.5.4 Digital Subtraction Angiography

Digital subtraction angiography (DSA) is generally performed in selected cases. In

patients with carotid artery disease, it is required during the arterial stenting proce-
dure or, less frequently, in case of discordances between other noninvasive methods.
In case of acute mesenteric ischemia, it has a pivotal role for a preoperative
evaluation, although it cannot be performed in critical state patients. In subjects
6 Vascular Diseases in Geriatric Patients 143

with chronic mesenteric ischemia, it allows a therapeutic approach, besides a diag-

nostic evaluation.
In addition, it is a fundamental tool for assessing arterial territories distal to the
knee, which are not well studied with other noninvasive techniques [8].

6.6 Features of Vulnerability of the Atherosclerotic Plaque

The atherosclerotic plaque may show some features that might increase the risk for
stroke, which can be detected through diagnostic imaging evaluation. The presence
of intraplaque hemorrhage, a lipid-rich necrotic core (LRNC) and the assessment of
the fibrous cap is well evaluated with MRI. In particular, CT is able to detect the
lipidic plaque components as well, but MRI better discriminates between LRNC
and intraplaque hemorrhage. In addition, MRI also provides information about a
thin or damaged fibrous cap.
Moreover, a plaque is considered active when intraplaque inflammation and neo-
vascularization are detected, better estimated with a CT scan.
Other information about plaque vulnerability are obtained with the evaluation of
plaque thickness and surface morphology, both well analyzed through DUS, CT,
and MRI. In particular, among the three possible types of plaque surface (smooth,
irregular, or ulcerated), the ulcerated form has the major risk for stroke.
Finally, it is useful to assess the volume of the plaque, with MRI providing better
information about soft tissue contrast and CT allowing a better spatial resolu-
tion [12].

6.7 Treatment

The main therapeutic strategy is to remove the cardiovascular risk factors, through
healthy life choices and medications. In addition, regular walking exercise is able to
increase the development of the collateral circulation, improving the claudication
pain. Finally, the last therapeutic approach is revascularization, performed in
patients with critical ischemia (Practice 2016).

6.7.1 Aneurysms

Another condition, typical for old adults, is the development of aneurysms, found in
the 3–4% of subjects older than 65 years of age, more frequently in the infrare-
nal aorta.
Aortic aneurysms are defined as a weakness of the aortic wall with the presence
of an aortic diameter >30 mm and an increase of more than 50% with respect to the
normal vessel, determining a dilatation with a saccular or fusiform morphology. The
aneurysms with a diameter >55 mm in men and >50 mm in women are at risk of
rupture.
144 G. Caredda et al.

Table 6.3 Determining agents for the development of aortic aneurysms

Determining factors for aortic aneurysms

Idiopathic
Genetic predisposition
Old age, male sex
Tobacco smoking
High DLD levels
Hypertension
Connective tissue disorders (Takayasu arteritis, Marfan syndrome)
Traumas
Infections (brucellosis, salmonellosis, tuberculosis)
LDL low-density lipoprotein [13]

Although mostly asymptomatic, in some patients they may lead to abdominal

and back pain and other nonspecific symptoms before rupture, which is often fatal.
They are mostly determined by nonspecific causes, but, in other cases, they are
induced by genetic predisposition, connective tissue disorders, infections, traumas,
smoking, obesity, high levels of low-density lipoprotein (LDL), and other factors,
which are summarized in Table 6.3 [13, 14].
Consequently, these causes lead to alterations of the elastic fibers of the extracel-
lular matrix, because of the activation of elastolytic processes by means of metal-
loproteinases (MMP). Besides, a concurrent determinant is the presence of chronic
parietal inflammation, with an infiltration of the arterial wall mostly by macro-
phages and lymphocytes [14, 15].

6.8 Diagnosis

In most cases, aneurysms are an incidental finding, casually noticed in other exami-
nations or identified thanks to their typical calcifications pattern. In other subjects,
they are clinically detected because of the presence of an abdominal palpable mass.
However, more frequently aneurysms are recognized through diagnostic imaging.
US, CT, and MR imaging (MRI) are the methods usually performed in order to
obtain aneurysm’s information such as its diameters [13–16]. The important mea-
surements that should be evaluated when assessing an aortic aneurysm include the
aneurysmal sac, the arterial portions proximal and distal to the dilatation, and the
features of the vascular access that would be used in case of stent-graft positioning,
in particular the ilio-femoral tract, including calcifications and thrombi [16].

6.8.1 Ultrasound

In patients with a non-ruptured aneurysm, US and DUS are the main techniques for
disease screening and monitoring. Indeed, they are noninvasive methods which
allow arterial diameter measurement with high reproducibility.
6 Vascular Diseases in Geriatric Patients 145

Besides, pulse-wave imaging (PWI) is able to identify the mechanical changes in

the arterial wall, and the pulse-wave velocity (PWV) provides the clinician with
important information about regional parietal changes.
Finally, the use of contrast agents in ultrasonography is a fundamental tool in the
follow-up of patients treated with endovascular aneurysm repair (EVAR), especially
in subjects who cannot undergo CT or MRI scans [14].

6.8.2 Computed Tomography

With 2D imaging, MIP and MPR images, CT angiography is able to assess the
aneurysm’s diameters, providing important information about the necessity for
operative treatment.
Before contrast administration, a first scan is useful for identifying parietal cal-
cifications in the aorto-iliac tract. An important pitfall that should be considered is
represented by vascular tortuosity, which might lead to obtain an erroneous value of
the vessel diameters, as well as their measurement in an axial plain.
In addition, CT has a pivotal role in examining the vascular anatomy for a proper
procedural planning, identifying the correct device suitable for the single patient, by
assessing the aorto-iliac length and the aneurysm’s diameters.
Finally, CT has a higher sensitivity than conventional angiography in identifying
the possibility of procedural and post-procedural complications, especially after
EVAR, more frequently represented by endoleaks [14, 16].

6.8.3 Magnetic Resonance

MR angiography without contrast administration is a valuable option for patients

who cannot undergo a CT examination, because of radiation exposure or risk for
nephrogenic systemic fibrosis in subjects with chronic renal disease. Although it
shows the same accuracy of CT in assessing the aortic diameters, it is not able to
analyze small vascular structures such as accessory renal arteries, especially when
their diameter is <2 mm, not to mention the impossibility for MRI to evaluate the
parietal calcifications. For this reason, according to Picel and colleagues, CT scan
without contrast agents should be performed in combination with an MRI examina-
tion [14, 16].
Moreover, MR angiography is able to recognize the presence of vascular
endoleak in cases not identified with a CT scan [14].

6.8.4 Functional Imaging and Molecular Imaging

The last studies analyze the disease from a wider point of view, considering not only
the vascular diameters but also the properties of the arterial wall. Indeed, a different
risk of progression and rupture has been observed in aneurysms with similar
146 G. Caredda et al.

diameters. The use of particular tracers (i.e., radio-labeled blood cells) allows the
localization of inflammatory and metabolic changes in the vascular walls. The main
technique used for functional imaging is single-photon emission computed tomog-
raphy (SPECT) with the employment of radioisotopes such as 99mTc, 111In, 123I, and
131
I. With this technique, the activity of the parietal thrombi can be evaluated, by
detecting the focal activity of platelets and polymorphonucleates [14].
Several molecular probes are also used with techniques such as MRI, magnetic
resonance spectroscopy (MRS), PET, optical bioluminescence, optical fluores-
cence, and targeted US. In the different stages of the disease, alterations in particu-
lar markers are detectable, providing important information that go beyond the
measurement of the vascular diameter by itself. Indeed, an increment of the parietal
activity is considered expression of wall inflammation, correlated with a major risk
of rupture. Even modifications in extracellular components such as elastin and col-
lagen are indicative for parietal instability, and thus increased risk of rupture [13,
14]. For instance, MRI images can be acquired using a particular probe, which
consist in the ultrasmall superparamagnetic particles of iron oxide (USPIO), which
marks areas of inflammation by detecting the activity of the macrophages. All of
these information provided can be used as a guide for appropriate pre-procedural
decision-making [15].

6.9 Treatment

If the aneurysm diameter is >5–5.5 cm or it increases >1 cm per year, a vascular

reparation is necessary. In the past, an open repairing was performed, but nowadays
an endovascular abdominal aneurysm repair (EVAR) is preferred, due to its post-­
procedure mortality rate of 4.7% compared to that (19.2%) of the open repair tech-
nique. A metallic stent secured at the proximal and the distal edges of the dilatation
creates a preferential passage for the blood into the vessel, excluding the dilated
portions [16].
In treated patients, imaging follow-up is necessary, with CT and CTA represent-
ing the gold standard. MRA is another surveillance option. US and nuclear imaging
can be useful in some cases, the latter especially in case of endograft infection [17].
If the diameter of the aneurysm is >5.5–6.5 cm, the perioperative risk is increased
and the same occurs for the risk of complications [16].
EVAR procedure is not free from complications. The most frequent one is the
development of endoleaks, the presence of blood flow in the aneurysmal sac, which
is not completely excluded by the endograft. It is present in about the 15–30% of
patients, usually 30 days after EVAR. Five types of endoleaks might be recognized
(see Table 6.4), types I and II being the most frequent (Figs. 6.4 and 6.5).
Endograft migration is another complication, named as the displacement of the
endograft >5–10 mm. Endograft contamination (early occurrence) or colonization
from a distant site of infection (later occurrence) may lead to endograft infection,
which is characterized by a high mortality rate, usually due to septic shock.
6 Vascular Diseases in Geriatric Patients 147

Table 6.4 Types of endoleaks and causes of occurrence [17]

Type of
endoleak Cause
Type I IA: anomaly in the adhesion of the proximal site of the graft
IB: anomaly in the adhesion of the distal site of the graft
Type II Patent aortic branches cause the presence of blood flow into the aneurysmal sac
Type III Alteration in the graft structure
Type IV Presence of pores in the endograft
Type V Increasing dilatation of the aneurysmal sac without imaging signs of endoleak
(“endotension” phenomenon)

a b

Fig. 6.4 (a, b) A 81-year-old male patient with AAA. The CTA shows the presence of infrarenal
aneurysm with endoluminal moderate eccentric thrombus (white arrows)

a b

Fig. 6.5 (a, b) A 75-year-old male patient with AAA. The CTA shows the presence of infrarenal
aneurysm with endoluminal severe eccentric thrombus (white arrows)
148 G. Caredda et al.

Other less frequent complications are represented by occlusion/kinking/collapse

of the graft limbs and systemic complications, such as organs ischemia, cerebrovas-
cular events, and post-implantation syndrome (an inflammatory/immune response
as a reaction to the endograft’s material, with systemic inflammation clinical signs
and symptoms).
Finally, in some cases, an open surgical conversion may be necessary, i.e., in
cases of symptomatic type V endoleaks or huge graft displacement [17].

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Airway Diseases in Geriatric Patients
7
Maurizio Balbi, Roberta Eufrasia Ledda, Silvia Pamparino,
Gianluca Milanese, Mario Silva, and Nicola Sverzellati

Abbreviations

B/A Broncho-arterial
BAF Bronchial anthracofibrosis
COPD Chronic obstructive pulmonary disease
CT Computed tomography
CXR Chest radiography
DTS Digital tomosynthesis
FEV1 forced expiratory volume in 1 second
FVC Force vital capacity
HRCT High-resolution CT
HU Hounsfield unit
ILD Interstitial lung diseases
LAC Large airway collapse
TD Tracheal diverticula

M. Balbi · R. E. Ledda · G. Milanese · M. Silva · N. Sverzellati (*)

Scienze Radiologiche, Department of Medicine and Surgery (DiMeC), University of Parma,
Parma, Italy
e-mail: [email protected]; [email protected]; [email protected];
[email protected]; [email protected]
S. Pamparino
Department of Health Sciences (DISSAL), Ospedale Policlinico San Martino, University of
Genova, Genoa, Italy

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 151
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_7
152 M. Balbi et al.

7.1 Introduction

Lung development starts in utero and continues postnatally up to 25–30 years of

age [1, 2]. From that point on, pulmonary function progressively declines, even in
the absence of overt pulmonary disease [3]. The aging lung shows (1) a progres-
sive decrease of alveolar surface area, (2) dilatation of airspaces, (3) reduced
mucociliary clearance, and (4) decreased elasticity [4, 5]. These phenomena are
sustained by cellular changes that impact structural, functional, and mechanical
properties of the respiratory system, yet the precise underlying molecular mecha-
nisms are poorly understood [6]. It has been suggested that the remodeling of the
extracellular matrix, with the resulting degradation of elastin and collagen fibers,
accounts for a major mechanism of the aging lung at the cellular level [7].
Furthermore, the aging process is well-known to be associated with a chronic,
low-grade, systemic inflammation, referred to as “inflamm-aging,” characterized
by higher levels of several cytokines, including interleukins 1 and 6, and tumor
necrosis factors alpha [6]. The number of airway neutrophils is higher in older
individuals, regardless of the presence of airway diseases, and peripheral neutro-
phils show elevated primary granule release and neutrophil elastase activity,
increasing the risk of airways wall damage [8].
As a consequence of such changes, the elderlies (>65 years of age) show lower
pulmonary oxygenation and reduced exercise capacity as well as enhanced sus-
ceptibility to pulmonary diseases, both chronic, such as chronic obstructive pul-
monary disease (COPD) and interstitial lung diseases (ILD), and acute/subacute,
including pulmonary infections [5]. With greater life expectancy, understanding
the imaging appearance of the healthy aging lung is of utmost importance to dis-
tinguish a disease state from age-related physiological changes [2–6, 9]. Most
information about the effects of age on the respiratory system has come from
histopathologic examination and pulmonary function testing, while the role of
imaging in phenotyping the so-called senescent lung has been relatively marginal
[10, 11]. As a result, the borderland between normal and abnormal airway imag-
ing appearance in the elderly is, to some degree, still lined within a “gray
area” [12].
Current evidence on radiological age-related normal and pathological changes of
large and small airways will be discussed herein.

7.2 Imaging Techniques

A comprehensive discussion of the radiological techniques currently used in clini-

cal practice for the evaluation of the airways and their current limitations goes
beyond the scope of this chapter. In this paragraph, general considerations will be
made, while detailed technical aspects pertaining to specific disorders will be treated
in the following sections.
7 Airway Diseases in Geriatric Patients 153

7.2.1 Chest Radiography (CXR)

Chest radiography (CXR) remains the first-line imaging for many thoracic diseases,
showing a generally good performance as a screening evaluation [13]. If the accu-
racy of such modality is rather limited for evaluating small airways due to intrinsic
limitations (i.e., limited resolution and superimposition of overlapping structures),
large airway abnormalities can be relatively easily demonstrated on radiographic
images, regardless of age [14]. Digital chest radiography has continuously and sig-
nificantly improved over the last decades, with several processing tools being imple-
mented to support radiologists in the detection of pathological findings, including
digital tomosynthesis (DTS) and dual-energy subtraction techniques [15, 16]. DTS
has been demonstrated to overcome conventional radiography in the assessment of
central airways, improving their coronal view and thus facilitating the identification
of a suspected either ingested or aspirated foreign body, which may be of value in
geriatric patients [17]. Analogously to DTS, images obtained with dual-energy sub-
traction improve the detection of tracheal abnormalities. Tracheal stenosis and nar-
rowing due to extrinsic compression can be, in fact, more easily demonstrated on
soft-tissue-selective images [18].
Such techniques, however, are not free of limitations, including their relatively
low availability, whereas chest CT, considered the imaging modality of choice, is
much largely accessible.

7.2.2 High-Resolution Computed Tomography (HRCT)

Chest high-resolution CT (HRCT) is the current imaging modality of choice for the
evaluation of airways. The two consistent components of HRCT include the use of
thin sections (≤1.5 mm) coupled with a high spatial frequency reconstruction algo-
rithm [19]. Although there are no standardized HRCT protocols for the assessment
of the airways, acquisition of volumetric scanning has several advantages compared
to interspaced scanning (i.e., obtained with 10–20 mm intervals between axial
scans), which is prone to miss focal abnormalities. Volumetric HRCT allows both
the evaluation of the airways in a true cross-section using multiplanar reconstruc-
tion and application of post-processing techniques (e.g., minimum intensity projec-
tion and maximum intensity projection) as well as quantitative software [19, 20].
Technical parameters ought to be optimized to avoid motion artifacts, which
deserve particular attention in the elderly. Possible strategies include caudocranial
scanning, increased pitch, and faster rotation time [21]. The window setting used to
interpret HRCT images is of utmost importance since it may significantly affect the
apparent bronchial walls thickness, best assessed with window width centers
between −250 and −750 HU and window width >1000 HU. Other settings, particu-
larly window width <1000 HU, can lead to a substantial artificial thickening of
bronchial walls [22].
154 M. Balbi et al.

Although a higher radiation exposure remains the major drawback of CT as com-

pared to other techniques (i.e., CXR), it has been progressively overcome with con-
tinuous implementation of a variety of radiation dose reduction techniques [23, 24].

7.3 Normal Aging

7.3.1 Trachea and Main Bronchi

The trachea is considered to increase in size and become irregular in shape over
time. Gibellino et al. observed a significant difference in tracheal diameters and
cross-sectional area between a group of supposed healthy young men (n = 18; mean
age, 21.1; mean coronal diameter, 1.79 cm; mean sagittal diameter 2.00 cm; mean
cross-sectional area, 2.81 cm2) and middle-age men (n = 32; mean age, 52.2; mean
coronal diameter 1.91 cm; mean sagittal diameter 2.14 cm; mean cross-sectional
area, 3.22 cm2) [25]. However, neither patients greater than 61 years of age nor
women were included in the analysis. Despite the small sample size and the rela-
tively young subjects included, these results were in keeping with a previous study
that observed a nearly steady increase in sagittal and coronal tracheal diameters
from the third decade onward in 808 healthy subjects aged 10–79 years (430 males
and 378 females) measured on radiographic images [26]. Collins et al. confirmed a
significant positive correlation between age and radiographic tracheal size (r values
between 0.324 and 0.603; p < 0.01) in 165 healthy nonsmokers (79 male and 86
females; mean age, 50 years) [27]. By means of computed tomography (CT), Sakai
et al. demonstrated a significant positive correlation between tracheal area and age
(r = 0.37; p = 0.0006) in 83 healthy male volunteers aged 21–83 years (mean age,
47.7 years) [28]. The same study also demonstrated that the trachea tends to become
more irregular in shape with increasing age, as proven by a loss in its circularity
(r = −0.32; p = 0.003) [28].
A more recent study, where 81 healthy volunteers aged 25–75 years (40 female
and 41 male) underwent a chest CT at total lung capacity and during forced exhala-
tion, showed that older men (mean age, 61.8 years) had 12% greater cross-sectional
total area at total lung capacity than younger men (mean age, 32.2 years) (p = 0.02).
However, no subjects aged >75 years were enrolled [29]. Most notably, men, but not
women, showed a significant positive correlation between the percentage of airway
collapse and age (R2 = 0.40; p < 0.001) up to and exceeding the value of 50%, which
represents the most reported threshold to define large airway collapse (LAC) [30].
These results have extended knowledge in the age-related changes of the trachea,
suggesting that both age and sex should be considered in the diagnostic evaluation
of expiratory dynamic airway collapse to not mistake a normal response to expira-
tory maneuvers for a disease state.
Tracheal cartilaginous rings can become calcific as an age effect. This finding is
almost always incidental and does not have a recognized functional significance
(Fig. 7.1). In a chest radiographic series, it was reported in 37% of patients aged
75 years or older [31]. Lloyd et al. described tracheobronchial calcification in 26%
7 Airway Diseases in Geriatric Patients 155

a b

Fig. 7.1 (a, b) Coronal unenhanced CT images of a 79-year-old woman show tracheobronchial
calcification rings. In (b), the calcifications are magnified by means of maximum-intensity-­
projection (MIP) reconstruction

of patients aged 40–45 years and in up to 65% of men and 40.5% of women aged
60–79 years undergoing chest CT for a wide range of suspected both mediastinal
and pulmonary disorders [32]. Of note, tracheal calcification is not an exclusive
manifestation of normal aging but has been associated with other conditions, includ-
ing adrenogenital syndrome, diastrophic dysplasia, and a history of warfarin ther-
apy [33]. When nodular in shape (8–10 mm) and adjacent to thickened tracheal
cartilage, calcifications may result from a benign disorder called tracheobroncho-
pathia osteochondroplastica. In this condition, however, the trachea appears much
more irregular in shape than normal, making the diagnosis quite straightfor-
ward [34].

7.3.2 Airway Wall Thickness

Current evidence on age-related changes in airway wall thickness is somewhat con-

flicting. In a study by Matsuoka et al., no difference was observed in the ratio
between the bronchial wall thickness and the bronchial total diameter measured on
CT images of 85 healthy volunteers aged 21–90 years (mean age, 74 years) [35].
Conversely, using the accompanying pulmonary artery for comparison, Copley
et al. found a higher frequency of bronchial wall thickening in older (>75 years)
than younger (<55 years) asymptomatic subjects (p < 0.001) [36]. In these studies,
CT scans were acquired using non-contiguous sections (see High-Resolution CT
paragraph), and airway wall thickness was either measured manually [35] or evalu-
ated by a point scale [36]. More recently, Telenga et al. found a significant (p < 0.001)
156 M. Balbi et al.

association between higher age and a lower airway wall thickness at an internal
parameter of 10 mm (i.e., a standardized measurement of airway wall thickness
obtained from the regression line between the square root of the airway wall area
and the internal perimeter of the airway) in 99 healthy subjects (median age,
39 years; interquartile range, 22–54) [37]. Such measurements were performed
using an automated software, potentially more reproducible and accurate than man-
ual measurements [38]. These results are partly in keeping with those of Zach et al.,
who demonstrated a significant (p = 0.006) decrease of wall area percent (i.e., wall
area/total bronchial area) and an increase of internal lumen area with age in a cohort
of 92 healthy subjects aged 45–80 years [39].
It is worth emphasizing that no established criteria exist to define bronchial wall
thickening, which remains a subjective diagnosis. Moreover, current CT metrics to
evaluate bronchial wall thickness are affected by potential bias, such as lung vol-
ume, reconstruction parameters (i.e., see High-Resolution CT paragraph), underly-
ing airway disease, and limited capability of CT of distinguishing bronchial wall
from peribronchovascular interstitium [40, 41]. Of note, bronchial wall thickening
can be underestimated when the bronchial diameter is used for comparison in
patients with bronchial dilation (e.g., in case of bronchiectasis or suboptimal infla-
tion). In contrast, thickening of the peribronchovascular interstitium may result in
what appears to be bronchial wall thickening. Therefore, the effects of age on air-
way wall thickness are not easy to be ascertained.

7.3.3 Bronchial Caliber

The most used descriptive parameter to evaluate bronchial caliber is the broncho-­
arterial (B/A) ratio, which is obtained by dividing the diameter of the bronchus
(most commonly the internal bronchial diameter) by the diameter of the adjacent
pulmonary artery. As a rule of thumb, the B/A ratio is regarded as abnormal when it
exceeds the value of 1, meeting the radiological definition of bronchiectasis [42].
There is evidence that the B/A ratio increases with age, reaching bronchiectatic
dimensions in some cases (Fig. 7.2). Matsuoka et al. found a significant correlation
between the B/A ratio and age (r = 0.768, p < 0.0001) in a group of 85 healthy sub-
jects. The B/A ratio was greater than 1 in 41% of subjects aged >65 years and in 7%
of subjects aged between 41 and 64 years but in no subjects aged between 21 and
40 years [35]. As stated above, Copley et al. observed that bronchial dilation was
more prevalent in older (>75 years) than younger (<55 years) healthy subjects (60%
vs. 6%; p < 0.001) [36]. Moreover, bronchial dilation was found to present a lesser
extent in the younger than in the older group (p < 0.001), in which it also showed a
lower lobe predominance (i.e., 80% of cases) [36].
Notably, an increase of the B/A ratio can be driven, at least to some extent, by a
diameter reduction of the pulmonary arteries rather than a true bronchial dilation. This
phenomenon can be due to a disease state (e.g., asthma) [43] but also found in healthy
subjects, including those who live at high altitudes (exposed to hypoxia) [44] and never
smokers [45]. Nevertheless, the lack of standardized age-specific reference values of
7 Airway Diseases in Geriatric Patients 157

a b

Fig. 7.2 (a) Axial unenhanced CT image of a healthy 23-year-old-man shows a broncho-arterial
ratio <1 (arrow) at the right lower lobe posterior segment. (b) At the same level, the broncho-­
arterial ratio is >1 (arrow) in a 70-year-old-man with no history of cardiopulmonary disease.
Recognition of an age-related increase of broncho-arterial ratio is essential to avoid a bronchiecta-
sis overdiagnosis in otherwise healthy older individuals

airway and vessel size currently prevents understanding how they relate to each other
with increasing age. Despite these well-known limitations, recognizing a B/A ratio
greater than 1 as a possible age-related finding is essential to reduce the chance of a
spurious diagnosis of “bronchiectasis” in an otherwise healthy old individual.

7.3.4 Small Airways

Given the limited resolution of CT in the visualization of airways <2 mm in diameter,

the radiological evidence of small airways aging rests upon the evaluation of abnor-
mal retention of air in the lung as a surrogate of obstruction, namely the air trapping
[46]. This finding is demonstrated on CT expiratory scans as parenchymal areas with
less than normal increase in attenuation and lack of volume reduction [47, 48]. Areas
of air trapping can be seen in up to 80% of healthy subjects and with increasing fre-
quency and extension over time, usually not exceeding 25% of the whole lung volume
[49, 50]. In a study by Lee et al., air trapping was found in 3 out of 13 (23%) subjects
158 M. Balbi et al.

aged 21–30 years, 7 of 17 (41%) aged 41–50 years, 11 of 17 (65%) aged 51–60 years,
and 13 of 17 (76%) aged 61 years or older [51]. The increase in the frequency of air
trapping with age was found statistically significant (p < 0.05), as well as the correla-
tion between air trapping extension and age (r = 0.523, p < 0.001) [51]. Thus, it was
suggested that airway occlusion or luminal narrowing might occur with normal aging,
although only a few over 75-year olds were included, and no histological sample was
obtained. Subsequent work extended these findings by exploring a larger population
of more advanced age and providing data from lung specimens. By means of paramet-
ric response mapping (i.e., a voxel-­based image analysis that classifies lung by thresh-
olding Hounsfield unit, HU, values from spatially aligned inspiratory/expiratory CT
scans), Martinez et al. found that nonemphysematous air trapping increased by 2.7%
per decade in a population of 580 never- and ever-smokers free from obstruction and
respiratory symptoms (i.e., from 3.6%, if aged 40–50 years, to 12.7% when aged
70–80 years) [52]. Increasing air trapping was associated with increased force vital
capacity (FVC) (p = 0.004) but unchanged forced expiratory volume in 1 second
(FEV1) (p = 0.94), yielding lower FEV1/FVC ratios (p < 0.001) [52]. In keeping with
these results, Verleden et al. demonstrated an age-dependent loss of terminal bronchi-
oles in 32 never-smoker lung donors (age range 16–83 years) using a combination of
ex vivo CT, whole lung micro-CT, and micro-CT of extracted cores. The loss of ter-
minal bronchioles (i.e., about half of the total number of terminal bronchioles between
30 and 80 years of age) was corroborated by the association of the predicted pulmo-
nary function with the total number of terminal bronchioles, suggesting that loss of
small airways is a relevant structural component of age-related decline in pulmonary
function of healthy individuals [53].
Of note, age-related changes in CT lung density are not exclusively attributable
to a small airway involvement. Several studies have focused on the presumptive
relationship between the physiological decrease in lung density with age (i.e.,
approximately 50 HU between 20 and 70 years of age) and the progressive enlarge-
ment of the airspaces over time, a phenomenon conventionally mislabeled as “senile
emphysema” (despite the absence of destruction of alveolar walls, implicit in the
word emphysema) [54–57]. In non-smoker elderlies, lung attenuation possibly
approaches and even falls below the density thresholds commonly used to define
emphysema (i.e., 910 HU or 950 HU), demanding caution when applying densitom-
etry in aging lungs to avoid mistaking normal parenchyma for damage [57, 58].
Nevertheless, recent evidence suggests that age-related emphysematous changes
may be of limited importance because of their low extent (i.e., <5% of the whole
lung) and substantial stability over time (i.e., increase of about 0.1% per 10 years
between the 50 and 80 years of age) [52].

7.4 Pathological Conditions

7.4.1 Chronic Obstructive Pulmonary Disease (COPD)

Chronic obstructive pulmonary disease (COPD) represents the fourth leading cause
of death worldwide, with increasing prevalence in the elderly [3]. The estimated
prevalence of COPD is more than 390 million people worldwide in 2030 [59]. To
7 Airway Diseases in Geriatric Patients 159

date, various phenotypes of COPD have been described, with chronic bronchitis and
emphysema accounting for the most common ones. The former is characterized by
predominant airway-related changes (inflammation and airway wall thickening)
with increased mucus production, whereas the latter by alveolar wall destruction
and hyperinflation, resulting in impaired gas exchange [60]. Notably, it has been
suggested that the small airway damage represents the primum movens of such het-
erogeneous disorder, even in the emphysematous phenotype [61].
Regardless of the phenotype, establishing the presence of COPD in the elderly
can be quite challenging due to the significant morphological similarities between
aged lung and COPD. The physiological airspace enlargement without the alveolar
wall destruction observed in COPD is often erroneously labeled as “senile emphy-
sema” [62, 63]. The risk of such misinterpretation is over-diagnosing COPD within
the geriatric population, potentially leading to unnecessary investigations. Having
said that, it is worth emphasizing that the diagnosis of COPD relies on both clinical
and functional evidence of expiratory airflow obstruction [64], whereas imaging
(mainly CT) normally serves the purpose of assessing the disease extent (emphyse-
matous phenotype) and exacerbations (bronchitis phenotype). Measurement of
emphysema severity by means of CT densitometry techniques has been established
in the literature [65, 66], and different quantitative approaches—whose discussion
would deserve a dedicated chapter—have been employed more recently [67–69].
Chronic bronchitis is demonstrated by a relative increase in bronchial wall thickness
as compared to the bronchial lumen and with the diameter of adjacent pulmonary
arteries, a rather subjective morphological feature, as discussed above, while poorly
defined centrilobular nodules of ground-glass attenuation represent small airway
inflammation [70].
Pulmonary cysts deserve special attention since they can be misinterpreted as
bullous emphysema, although they represent an independent entity. The depiction
of thin-walled air spaces on CT may help distinguish pulmonary cysts from emphy-
sema [71].

7.4.2 Bronchiectasis

The term bronchiectasis refers to a clinico-radiological entity characterized by an

irreversible abnormal dilatation of the bronchial tree, secondary to a combination of
inflammation and obstruction/impaired clearance [72]. The most common clinical
manifestations include chronic productive cough and dyspnea, whereas fatigue,
hemoptysis, and thoracic pain are less common [73].
Although older bronchiectatic patients experience a worse quality of life and die
more frequently during the 3-year follow-up as compared to younger affected sub-
jects, no significant differences have been observed in terms of systemic inflamma-
tion levels and exacerbation rates across all age groups [72, 74], suggesting that
comorbidities play a role in such a clinical and prognostic discrepancy.
It has been hypothesized that the bronchial dilation and bronchial wall thicken-
ing observed in the elderly population can be partly due to impaired large and small
airway clearance mechanisms, secondary to a less effective mucociliary function
and a decreased cough reflex, both contributing to mucus retention [75]. Recognized
160 M. Balbi et al.

etiologies of bronchiectasis include infections (25%), COPD (13%), connective tis-

sue diseases (7.1%), and immunodeficiency (4.5%). Nevertheless, a non-negligible
proportion of patients (36%) remains diagnosed with idiopathic bronchiectasis. If
bronchiectasis related to asthma, inflammatory bowel disease, and ciliary dysfunc-
tion is more prevalent in younger adults, COPD-related bronchiectasis occurs more
frequently in older adults and elderly patients [76, 77].
The gold standard imaging modality for diagnosing bronchiectasis remains chest
HRCT [78]. The three most used radiological criteria to determine the presence of
bronchiectasis are represented by (1) increased B/A ratio (a ratio >1–1.5 has been
suggested to define bronchiectasis in adults) [78, 79], (2) lack of tapering, defined
as unchanged airway diameter for 2 cm after branching, and (3) visualization of
airways in the periphery of the lung, within 1 cm from the costal pleura or abutting
mediastinal pleural [47, 80]. Although these CT features are usually of limited value
to discriminate among different causes of bronchiectasis [81], the type of bronchi-
ectasis (i.e., cylindric, varicose, or cystic) [82], their distribution within the lung
regions, and concurrent ancillary findings might help narrow down the differential
diagnoses. Associated findings include mucus retention/impaction, bronchial wall
thickening, air trapping, and consolidation.
Bronchiectatic changes in the right middle lobe and lingula in older women
deserve special consideration since they have a high predictive value for
Mycobacterium avium–intracellulare complex (MAC) infection. When associated
with centrilobular nodules, scarring, and volume loss of the affected lobes, these
morphological abnormalities define the so-called Lady Windermere syndrome [83].
Traction bronchiectasis, secondary to pulmonary fibrosis, will not be discussed.

7.4.3 Large Airway Collapse (LAC)

LAC refers to an excessive inward movement of the trachea and/or main bronchi
during expiration [30]. LAC comprises two entities: tracheomalacia, where there is
softening of the cartilaginous rings, and excessive dynamic airway collapse, defined
by an exaggerated forward displacement of the posterior tracheal membrane [30].
This nomenclature suffers from limited consistency throughout the literature; hence,
the inclusive term of LAC will be used hereafter.
It is estimated that LAC affects about one out of ten patients undergoing bron-
choscopy for pulmonary complaints and as many as a third of patients with COPD
or severe asthma [30, 84, 85]. However, the true prevalence of this condition remains
difficult to ascertain due to heterogeneous populations and the diagnostic methods
of the available studies. LAC may go underrecognized because of associated respi-
ratory diseases with overlapping symptoms, such as COPD, asthma, and bronchiec-
tasis, which are regarded not only to mimic but even predispose to LAC [86, 87].
Other risk factors include prolonged intubation and longstanding extrinsic airway
compression [87, 88]. Interestingly, although the degree of airways collapse appears
to relate with age (in healthy male volunteers), a higher risk of developing LAC in
the elderly has not been proven so far [29].
7 Airway Diseases in Geriatric Patients 161

While dynamic bronchoscopy is still considered the diagnostic standard for

LAC, in a recent meta-analysis, Mitropoulos et al. observed that CT had been the
most reported modality to diagnose LAC over the past 30 years [30]. CT might
serve as a complement or, especially in the elderly, an alternative to bronchoscopy,
providing a rapid, noninvasive assessment of the central airways by means of inspi-
ratory and expiratory acquisitions. Regardless of the investigation modality, there is
still no agreement on what constitutes an “excessive” degree of collapse. At the time
of its first definition, in 1965, Rayl et al. considered the airway collapse to be abnor-
mal when the airway lumen decreased to at least half of its diameter during cough-
ing, assessed on bronchography [89]. From that point on, such a threshold has been
increasingly cited as “diagnostic” of LAC. However, when defined by >50% reduc-
tion of the airway lumen, LAC is over-diagnosed in about 17% of healthy subjects
[30, 84, 88]. The adoption of higher thresholds of collapsibility (i.e., 70%) has
shown promise in reducing the false-positive rate of LAC to about 2% [85].
Nevertheless, even when LAC approaches or exceeds this magnitude, it remains
challenging to decipher the relationship between the degree of collapse with symp-
toms and flow limitation [90]. The diagnosis of LAC should, therefore, not rely on
a mere imaging evaluation and be supported by the integration of data from bron-
choscopy, clinical evaluation, and pulmonary function.
Normal tracheal morphology, either oval or round, is the most typically
observed configuration on inspiratory CT images of patients with LAC. The inspi-
ratory “lunate” trachea has the appearance of laterally splayed tracheal cartilage
and excessive sagittal narrowing (i.e., coronal to sagittal diameter ratio >1), a
configuration that is highly specific but low sensitive for LAC [91–93] (Fig. 7.3).

a b

Fig. 7.3 Axial unenhanced CT images of a 76-year-old man show (a) increased ratio of coronal-­
to-­sagittal tracheal diameters (i.e., lunate trachea) and (b) excessive collapse of the posterior tra-
cheal wall (arrow) on expiration, highly suggestive of tracheomalacia. Advanced destructive
emphysema and bronchial wall thickening, consistent with a COPD diagnosis, can also be
appreciated
162 M. Balbi et al.

Expiratory airway collapse morphology includes: (1) an excessively bowed pos-

terior wall that approximates the anterior wall’s contour, resulting in the so-called
frown sign; (2) a “saber-shape” type, characterized by distortion of the normal
C-shape cartilage into an anteriorly elongated configuration with concomitant
transverse narrowing (i.e., sagittal to coronal diameter ratio >2); and (3) circum-
ferential narrowing, with a more isotropic reduction in airway cross-section [94].
This distinction is relevant since patients with an expiratory “frown-like” configu-
ration are considered good candidates for tracheoplasty, a surgical technique for
the treatment of LAC that involves reinforcement of the posterior membranous
wall of the trachea [95, 96].

7.4.4 Broncholithiasis

The term broncholithiasis refers to calcified or ossified material, called broncholith,

within the tracheobronchial tree, caused by either foreign body aspiration or calci-
fied lymph nodes. The broncholiths, composed of calcium phosphate (85–90%) and
calcium carbonate (10–15%) [97], are variable in size and usually irregular in shape.
They can be classified into three different types: endobronchial, peribronchial, and
transbronchial, based on their location within the tracheobronchial tree [98, 99]. In
general, broncholiths tend to occur more frequently on the right side (upper and
middle lobes in particular) due to the airway anatomy and intrathoracic lymph
nodes distribution [97].
The incidence of broncholithiasis is higher in areas of endemic tuberculosis and/
or histoplasmosis due to necrotizing granulomatous mediastinal lymphadenitis, but
any focal process responsible for dystrophic calcification, including sarcoidosis,
can potentially cause broncholithiasis [97, 100]. There is no established gender pre-
dilection, while the sixth and seventh decades of life seem to be the most
affected [101].
Clinical manifestations range from nonproductive cough to massive hemoptysis
and acute airway obstruction. Lithoptysis (expectoration of stones) is an almost
pathognomonic symptom but relatively uncommon (seen in 6–26% of cases) [97,
102]. Most common complications include massive hemoptysis, secondary to bron-
chial irritation from the stone or rarely to vasculobronchial fistula, and obstructive
pneumonia, whereas empyema, chronic lung abscess, mediastinal abscess, bron-
choceles, and middle lobe syndrome account for less common ones [97].
Broncholithiasis can be easily depicted on CT when there is either an endobron-
chial or a peribronchial calcified nodule associated with features of bronchial
obstruction, such as atelectasis, obstructive pneumonitis, or bronchiectasis (Fig. 7.4).
Unsurprisingly, thin collimation helical CT is superior to conventional CT in deter-
mining whether a calcified nodule is endobronchial in position, overcoming volume-­
averaging artifacts [100, 102]. Bone or wide window CT settings are usually of help
to confirm the presence of calcification/ossification and to better assess the mor-
phology of a broncholith. Differential diagnoses include calcified fungus ball, calci-
fied endobronchial tumors (e.g., carcinoid and hamartoma that can rarely occur
7 Airway Diseases in Geriatric Patients 163

a b

Fig. 7.4 Axial (a) and coronal (b) unenhanced CT images of a 70-year-old man presented with
hemoptysis show a calcified nodule within a right upper lobe bronchus (empty circle), consistent
with broncholithiasis

within the bronchi [103]), and rarer conditions such as tracheobronchial amyloido-
sis and tracheobronchopathia osteochondroplastica (see above) [102].
Surgical management is normally reserved for cases complicated by airway dis-
tortion, fistula formation, and massive hemoptysis, whereas a conservative approach
seems to be an appropriate option for asymptomatic or minimally symptomatic sub-
jects [97].

7.4.5 Tracheal Diverticula

Tracheal diverticula (TD) are outpouchings from the tracheal wall [104]. With the
advent of CT and its continuous technical implementations (i.e., improvements in
spatial resolution of multidetector CT and use of thin slices), the prevalence of such
anatomical abnormality has been progressively increasing, ranging from 2% to 8%
[105]. A gender predominance has not been demonstrated [104].
TD tend to involve the right posterolateral wall of the trachea at the level of T1–
T3 vertebral bodies, an unprotected space compared to the contralateral side. TD are
classified into congenital and acquired, with the latter normally encountered in the
elderly population. Acquired TD are thought to be secondary to increased
164 M. Balbi et al.

intraluminal pressure that would cause out-bulging through a weak part of the tra-
cheal wall or cystic distension of the mucous gland ducts [106, 107].
Although TD are usually asymptomatic, in some cases, they can be responsible
of recurrent respiratory tract infections, acting as a reservoir for secretions and
hemoptysis [106]. Larger diverticula (>30mm) have been reported to cause also
painful neck swelling, cervical abscess, dysphagia, cough—secondary to compres-
sion of the vagus—and dysphonia due to compression of the recurrent laryngeal
nerve [108].
CT generally shows small air bubbles connected to the tracheal lumen and sur-
rounded by a very thin wall (Fig. 7.5). The communication with the trachea, how-
ever, is clearly appreciated in half of cases only, and usually with larger diverticula.
These diverticula might also have a thicker wall and be multiloculated. It is worth
emphasizing that when there is very little air within the diverticulum, it appears as
a solid structure, often indistinguishable from a lymph node [104].

7.4.6 Bronchial Anthracofibrosis

Bronchial anthracofibrosis (BAF) represents a rather new pathological entity typi-

cally encountered in elderly females with a long-lasting biomass fuel smoke expo-
sure [109, 110]. BAF can be associated with other clinical conditions, such as
pulmonary tuberculosis (a coexistence as high as 50% has been reported), COPD,
pneumonia, and malignancy [111]. The prevalence of such a rare condition is quite
low in developed countries. Clinical presentation is nonspecific, including chronic
productive cough and dyspnea, and depends on the associated diseases [111].
BAF diagnosis is established when bronchial bluish-black anthracotic pigmenta-
tion and narrowing/distortion of the affected bronchus are observed on bronchos-
copy [112]. Nonetheless, CT evidence of multifocal bronchial narrowing along with
peribronchial cuffing and mediastinal lymphadenopathy—either calcified or non-
calcified—can raise the suspicion of BAF. Both segmental and lobar bronchi of the
right upper and middle lobes are the most affected ones. Sparing of the trachea and

Fig. 7.5 Unenhanced CT

image of a 70-year-old
man depicts an air-filled
right tracheal diverticulum
(arrowhead). There is a
thin communicating
channel between the
diverticulum and the
tracheal lumen (arrow)
7 Airway Diseases in Geriatric Patients 165

main bronchi is observed in most cases. Other CT features include collapse, con-
solidation, and mass lesions [113, 114].

7.5 Conclusions

Despite growing knowledge of cellular and molecular aging mechanisms, the bor-
derland between normal and abnormal airway imaging in the elderly is still difficult
to define. Distinguishing physiological age-related changes from a disease state
remains quite challenging in a non-negligible proportion of the geriatric population.
However, the role of imaging in the detection and stratification of airway diseases
has been well-established, with chest HRCT being increasingly employed in clini-
cal practice to support the management of patients suffering from airway disorders,
including the elderlies.

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Neoplastic Diseases of the Respiratory
System in Geriatric Patients 8
Zeno Falaschi, Francesco Filippone, Sergio Pansini,
Stefano Tricca, Paola Basile, Sara Cesano,
and Alessandro Carriero

8.1 Epidemiology

Lung cancer is the most common cancer in the world and the leading cause of
cancer-­related deaths in both Western countries and the United States, with the
fastest-­growing morbidity and mortality, especially in the elderly [1].
According to the latest statistics updated to 2020 of the American Cancer Society,
there will be 235,760 estimated new cases of lung cancer in 2021, of which 119,100
cases in male and 116,660 in females; on the other hand, the age-­adjusted death rate
for lung cancer is higher for men (46.7 per 100,000 persons) than for women (31.9
per 100,000 persons). This means that more men are diagnosed with lung cancer
each year, but more women live with the disease. In addition, these data also con-
firm that lung cancer is mostly a disease of the elderly, with a growing incidence
from 0.6% (in the age range from 50 to 59 years), to 5.4% (from 70 years and
older) [2].
Lung cancer refers to a histologically and clinically diverse group of malignan-
cies arising in the respiratory tract, primarily but not exclusively in cells lining the
airways of the lung. The four principal types, classified by light microscopy and
special stains, are non-small-cell lung cancer (NSCLC), which is the most common
type and it constitutes between 80% and 85% of all lung cancers, adenocarcinoma,
small-cell carcinoma (SCLC), and squamous cell carcinoma. Unfortunately, at the
time of diagnosis, the majority of patients already have metastatic disease, and a
systemic, palliative treatment is the primary therapeutic option. More than 50% of
advanced NSCLCs are diagnosed in patients older than age 65 years [3].

Z. Falaschi · F. Filippone · S. Pansini · S. Tricca · P. Basile · S. Cesano · A. Carriero (*)

Department of Diagnosis and Treatment Services, Radiodiagnostics, Azienda Ospedaliero
Universitaria Maggiore della Carità, Novara, Italy
e-mail: [email protected]; [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 171
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_8
172 Z. Falaschi et al.

8.1.1 The Role of Aging

There is worldwide-accepted evidence of a population shift toward older ages: the

current life expectancy in the United States is 78.7 years compared to 49 years in
1900. By the second half of this century, more than 20% of the population will be
older than 65 years, and this increased life expectancy reflects, in part, a better
understanding of the diseases, new interventions, and the success of public health
programs [4].
The open question is what age cutoff should be used to define “elderly.” In
Europe and in the USA, an age greater than 70 years is accepted to define this vari-
able. However, some authors define elderly patients in geriatric oncology as “old”
when their clinical status starts to interfere with oncologic decision-making [5].
Clearly, this shift favors an increased risk of developing disorders that are more
common at a more advanced age and lung cancer is one of them, since it is primarily
a disease of older populations with less than 0.5% of lung cancer-related deaths
registered at an age younger than 40 years [6].
Recent Surveillance, Epidemiology, and End Results data in the United States
suggest that the median age at diagnosis of lung cancer is 70 years and, what is
more, in the last decade, the incidence and the mortality from lung cancer have
decreased among individuals aged 50 years and younger but have increased among
those aged 70 years and older [7].
Aging is inextricably linked to physiologic changes in functional status, organ
function, and drug pharmacokinetics. For example, it is associated with decreases in
marrow reserve, drug clearance, and lean body mass. Furthermore, concomitant
comorbidities that affect functional status, general health, and tumor symptoms are
frequently present in this patient population and therefore the selection of their opti-
mal treatment is daunted. This risk is also increased by one of the major problems
in current practice, which is that the elderly are often excluded from participation in
clinical trials and receive untested or inadequate treatment based on the long-held
but completely unsubstantiated notion that cancer in older people is less aggressive
and that older patients are inherently incapable of tolerating the exigencies of treat-
ment, leading often to a substantial undertreatment of these patients [8].

8.1.2 Risk Factors

The rising incidence of lung cancer through the first half of the twentieth century
prompted intensive epidemiologic investigations of the disease, resulting in the
identification of a number of causal agents. Cigarette smoking is by far the largest
cause of lung cancer, and the worldwide epidemic of lung cancer is largely attribut-
able to smoking. However, occupational exposures, including asbestos, uranium,
and coke (an important fuel in the manufacture of iron in smelters, blast furnaces,
and foundries), have placed a number of worker groups at high risk, and some of
these occupational agents are synergistic with smoking in increasing lung cancer
risks [7].
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 173

In fact, nonsmoking asbestos workers are five times more likely to develop lung
cancer than nonsmokers not exposed to asbestos; if they also smoke, the risk factor
jumps to 50 or higher [9].
Furthermore there is some evidence that both indoor and outdoor air pollution
also increases lung cancer risks, specifically exposure to radon is estimated to be the
second-leading cause of lung cancer, accounting for an estimated 21,000 lung can-
cer deaths each year (range of 8000–45,000). Radon is a tasteless, colorless, and
odorless gas that is produced by decaying uranium and occurs naturally in soil and
rock. The majority of these deaths occur among smokers since there is a greater risk
for lung cancer when smokers also are exposed to radon [7].
In addition, observational evidence showing a familial aggregation of lung can-
cer has suggested that genetic factors also may determine risks in smokers, but the
specific genes remain under active investigation [8].

8.1.2.1 Smoke as the Main Risk Factor

Smoking has been shown to cause each of the major histologic types, although a
dose–response relationship with the number of cigarettes smoked varies across
types, being steepest for small cell carcinoma.
The causal link between smoking and lung cancer has been extensively investi-
gated at the molecular and cellular levels, and there is nowadays a quickly expand-
ing body of evidence that shows that the effects of tobacco smoke on cellular DNA
are quite consistent with the current conceptual model of carcinogenesis—a multi-
step process of genetic change. Lung cancers have been estimated to have more than
10 and perhaps as many as 20 genetic changes before any individual clonal tumor
emerges [10].
However, 40 years after smoking was first identified as a cause of lung cancer, it
remains a leading cause of cancer and of death from cancer. During the 1990s deaths
attributable to lung cancer declined significantly in men, while mortality rates in
women continued to increase. These patterns of incidence and mortality reflect
changes in smoking behaviors among US adults that occurred decades ago:
(National Cancer Institute (NCI) 1997). The smoking habit declined faster among
men than among women starting from the 1950s, and therefore the recent changes
in lung cancer incidence rates reflect these previous smoking attitudes [11].
Prior reports have fully described the variation of lung cancer risk with aspects
of smoking [12]. In smokers, the risk of lung cancer depends largely on the dura-
tion of smoking and the number of cigarettes smoked. The excess risks for smok-
ers, compared with people who have never smoked, are remarkably high. Many
studies provide RR estimates for developing lung cancer of 20 or higher for smok-
ers compared with lifetime nonsmokers. What is more, a risk-­free level of smok-
ing has not been identified, and even involuntary exposure to tobacco smoke
(second-hand smoke) increases lung cancer risks for nonsmokers. Instead, lung
cancer risk decreases with successful cessation and maintained abstinence: in fact
the data show that the RR for lung cancer among former smokers continues to
decline as the duration of not smoking increases in comparison with the risk
among continuing smokers, although it never reaches the level of risk of those
174 Z. Falaschi et al.

who have never smoked, even after 15–20 years of not smoking. Extensive data
convincingly show how smoking cessation lowers lung cancer risks: using data
from a 1990 case-control study, [13] estimated cumulative lung cancer risks for
persons up to 75 years of age. The estimated lifetime risk of lung cancer deaths
for men who continue to smoke, absent death from another cause, was 16%.
Substantial reductions in this risk can be achieved by cessation at younger ages;
even cessation at 60 years of age lowered the cumulative risk from 16% to about
10% [14].
Since the first research reports linking smoking to lung cancer and other dis-
eases, the tobacco industry has continually changed the characteristics of the ciga-
rette. These changes have included the addition of filter tips, perforation of the filter
tips, use of reconstituted tobacco, and changes in the paper and in additives.
Nevertheless, even though during the last 50 years characteristics of cigarettes have
changed and yields of tar and nicotine have declined substantially, as assessed by
the Federal Trade Commission’s test protocol, the risk of lung cancer in smokers
has not declined and the benefits are minimal in comparison with giving up ciga-
rettes entirely [15].
The single most effective way to reduce hazards of smoking continues to be that
of quitting entirely and the general pattern of this decline is the same for men and
women, for smokers of filter-tipped and unfiltered cigarettes, and for all major his-
tologic types of lung cancer [15].
In conclusion, despite the gains in understanding respiratory carcinogenesis and
the potential of molecular and imaging techniques to screen for lung cancer, smok-
ing prevention and cessation remain the fundamental strategies for controlling the
lung cancer epidemic.

8.1.3 Clinical Symptoms of Lung Cancer

One of the biggest problems in lung cancer diagnosis is that the symptoms are
shared with many benign pulmonary diseases and that they actually are more com-
mon in these pathologies.
As a matter of fact, lung cancer is usually asymptomatic in the early stages and
this often leads to a delay in the diagnosis, that occurs when the tumor is already in
an advanced stage.
Therefore, its symptoms are present only in a minority of the patients, are non-
specific, and appear only when the tumor has already spread.
Clinical presentation is heterogeneous, and it is caused by the local tumor growth,
the intrathoracic spread, and the distant spreading. It also depends on the tumor type
and its specific location and behavior. In fact, small-cell lung cancer (SCLC) gener-
ally arises in the central part of the lung, penetrates into the mediastinum, and con-
sequently is more commonly associated with invasive symptoms. On the contrary,
non-small-cell lung cancer (NSCLC) is usually located in the peripheral lung, and
it is characterized by less specific symptoms [9].
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 175

For what concerns local growth-related lung cancer symptoms, they mainly con-
sist of cough, dyspnea, wheeze, and hemoptysis.
Specifically, cough, which is caused by the obstruction of the airways, is the
most common symptom. It is present in almost 50% of the patients, and it is more
frequently associated with SCLC, since this tumor type is mainly located on larger
bronchi. Although cough is not specific for this pathology, with no doubt a new and
persistent cough in active or past smokers should raise concern for lung cancer. In
addition, recurrent pneumonia in the same anatomic region as well as frequent exac-
erbation of chronic obstructive pulmonary disease should be considered as alarm
signs [9].
On the other hand, hemoptysis is the most specific symptom, especially when
associated with others. This also has a higher positive predictive value compared to
the other symptoms. For this reason, every patient with hemoptysis should perform
a chest X-ray.
For what concerns symptoms related to the intrathoracic spread, these are caused
by the invasion of the tumor into the mediastinal structures and mainly consist of
chest pain, vocal cord paralysis, superior vena cava syndrome (SVC), and dysphagia.
In particular, SVC syndrome is caused by the obstruction of the vena cava by the
primary tumor or by enlarged lymph nodes or thrombus. It generally presents with
edema of the upper body.
Instead, vocal cord paralysis and dysphagia are caused by the invasion of the
recurrent laryngeal nerve and of the esophagus.
On the contrary, symptoms associated with the distant spreading of lung cancer
have mostly the same frequency in SCLC and NSCLC [10].
The most common metastatic sites are brain, liver, adrenal gland, bones, and
bone marrow. The central nervous system involvement frequently manifests with
headache, seizure, altered mental status; while bone metastases present with bone
pain, and liver metastases with anemia and weight loss.
In conclusion, lung cancer can also be associated with paraneoplastic syndromes
with SCLC as the most common cause [16]. Among these conditions, the most fre-
quent ones are syndrome of inappropriate antidiuresis, Cushing’s syndrome, and
hypercalcemia. In addition, SCLC can also be associated with neurologic syn-
dromes such as Lambert-Eaton and Limbic encephalitis.

8.1.4 Lung Cancer Diagnosis: General Features

The diagnosis of lung cancer can be done through chest X-ray, computed tomogra-
phy (CT) scans, magnetic resonance (MRI), positron emission tomography (PET),
cytology sputum, and breath analysis.
All the available detection techniques of lung cancer have different detection
levels and various markers. Nevertheless, it is often impossible to radiographically
distinguish between the several histological lung cancer types.
176 Z. Falaschi et al.

8.1.4.1 Chest X-Ray

Lung cancer is relatively infrequently found on chest X-rays due to the combina-
tion of difficulty in visualizing small lesions. The diagnostic confidence is the great-
est when the lesion is at least 8–10 mm [17].
Often it is impossible to radiographically distinguish between other histological
lung cancer types.
The appearance is related to the location of the tumor. Central lesions may appear
as a bulky hilum. Lobar collapse may be present when a bronchus is obstructed [18].
A more peripheral location may appear as a rounded or spiculated mass.
Cavitation may be seen as an air-fluid level.
Pleural effusion may also be seen, and it might be caused by either tumor diffu-
sion or venous obstruction [19].

8.1.4.2 Computed Tomography

The volumetric high-resolution CT (HRCT) is the gold standard for detecting and
characterizing lung lesions, eventually followed by iodine contrast infusion [20].
The low-dose CT is currently performed in PET-CT studies, or in a screening
setting.
Patients with suspected lung cancer should undergo a volumetric CT scan with
HR reconstructions even if the X-ray is normal.
While CT is a very sensitive method for establishing a detailed lymph node map,
its specificity is insufficient to determine whether the lymph nodes are malignant or
benign. Therefore, PET-CT is the gold standard [20].
Typically, a benign solitary pulmonary nodule (SPN) is smaller than 20 mm, has
regular contours, with low density values (e.g., fat or fluid), remains stable in dimen-
sions after 2 years, and does not show significant contrast enhancement [21].
Signs of malignancy usually consist of large dimensions (more than 30 mm),
irregular or spiculated contours with distortion of near vessels, peripheral ground
glass opacity (halo sign), may contain diffuse and small calcifications, volume dou-
bling time (VDT) of about 30–400 days, and show intense and rapid contrast
enhancement [22].
A lung nodule is a rounded or irregular region of increased attenuation. The
amount of attenuation can further classify the nodules as ground glass, subsolid, or
solid [23, 24].
Some types of lung cancer can show peculiarities.
The small-cell lung cancer (SCLC) can be central (60–70%) or peripheric
(30–40%). The latter is typically asymptomatic, has round shape and irregular con-
tours with a pleural tail. The bigger ones show central necrosis and/or excavation.
The central tumors extend into the mediastinal space and are usually rapidly
symptomatic. They show up as endo-bronchial masses with amorphous
calcifications.
This tumor can rapidly spread through the lymphatic and hemic ways [16, 25].
The carcinoid tumor is usually central, endo-bronchial located, determining
complete luminal-obstruction and lobar atelectasis or air trapping. It is often
2–5 cm large, has regular margins with micro-calcifications, highly vascularized
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 177

with intense contrast-enhancement. It has a slow growth so can reach very large
dimensions and can spread through the extra-bronchial space. Rarely it is
peripheric.
The adenocarcinoma may show different features based on the subtypes: the pre-­
invasive in situ minimally invasive adenocarcinoma and the invasive lepidic
predominant-­adenocarcinoma (formerly called bronchiolo-alveolar carcinoma,
BAC) often consist of ground glass nodule or a subsolid nodule with a predominant
ground glass component, while the remaining invasive subtypes of adenocarcinoma
usually show up as a solid or subsolid nodule.
The invasive mucinous adenocarcinoma subtype (also formerly mucinous BAC)
can have a variable appearance, including consolidation, air bronchograms, or mul-
tifocal subsolid nodules or masses [26].

Nuclear Medicine
FDG-PET/CT is essential for the lung cancer staging, since it can assess for the
nodal and distant metastatic disease.
Adenocarcinoma in situ, low-grade adenocarcinomas and minimally invasive
adenocarcinoma are commonly associated with PET false-negative results.
FDG PET/CT is recommended when assessing subsolid ground glass lung
lesions that have a solid component measuring more than 8 mm [20].

8.2 Lung Cancer: Role of the Chest X-Ray

8.2.1 Chest X-Ray: Role in Screening and Diagnosis

of Lung Cancer

Chest X-ray has a fundamental role in the diagnosis of many pulmonary diseases.
Due to its low cost, availability, and low radiation, it is usually the first exam per-
formed in order to diagnose lung pathologies. It is the first-line investigation in
patients with suspected lung cancer.
Lung cancer diagnosis may occur because of an incidental finding in an asymp-
tomatic patient that performs the exam for other reasons, in a symptomatic patient
or as an unexpected evolution from pneumonia, atelectasis, or pleural effusion.
Chest X-ray is often the first performed exam, but it is not the most sensitive
imaging technique. CT scan is considered the preferred exam to have a proper diag-
nosis and staging of the disease.
In fact chest X-ray sensitivity of lung nodule detection when it is <6 mm is very
low, but it increases when the nodule is calcified. The sensitivity is about 50% when
the nodule diameter is 6–10 mm [27].
Having an early diagnosis of lung cancer is associated with an improved sur-
vival; therefore, multiple studies have been performed to investigate the role of
chest X-ray in screening. Unfortunately, no study has demonstrated a reduction in
mortality connected to this exam. It has been shown that this technique fails to at
least initially detect lung cancer in more than 20% of patients.
178 Z. Falaschi et al.

The missed diagnosis may be related to “observer error,” to poor technique qual-
ity, but also to the dimension of the tumor. In fact, if it is less than 1 cm it can be
easily not detected. In addition, the location of the tumor may play a role, especially
when this is in the upper lobes where it can be masked by anatomical structures such
as ribs and vessels.
For these reasons, CT scan is the preferred technique to diagnose this disease [20].

8.2.2 Radiological Characteristics Based on Cellular Type

Lung cancer may present in different ways on chest X-ray: as a nodule, a mass, an
enlarged mediastinum, atelectasis, and pleural effusion.
Based on the cellular type of tumor, we can have different radiological character-
istics. However the histological subtype cannot be correctly identified solely on the
basis of chest X-ray, and a confirmative biopsy is always needed.

8.2.2.1 Adenocarcinoma
Adenocarcinoma is 31% of all lung cancers. It is usually peripherally located and
measures less than 4 cm. It is associated with detection of hila and/or mediastinal
enlargement on chest X-ray in 51% of cases.

8.2.2.2 Adenosquamous Carcinoma

This is only 2% of all lung cancers and normally presents as solitary and peripheral
nodule. Cavitation may be seen.

8.2.2.3 Squamous Cell Carcinoma

Squamous cell carcinoma is 30% of all lung cancers and is usually centrally located,
is often >4 cm and cavitation is frequently present.

8.2.2.4 Small-Cell Lung Cancer

It represents 18% of lung cancers and often present as bulky hila and mediastinal
lymph node masses.

8.2.2.5 Carcinoid Tumor

It is 1% of all lung cancers, and it is usually <2.5 cm and often associated with
obstructive pneumonia.

8.2.2.6 Large-Cell Lung Cancer

It is 9% of all lung cancers and is a histological diagnosis of exclusion [27].

8.2.3 Pulmonary Nodules and Masses

Pulmonary nodules are a very frequent finding on chest X-ray and their prevalence
ranges from 0.09% to 0.2%.
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 179

A solitary nodule presents as a well-defined, rounded opacity that measures less

or equal to 3 cm in diameter. Lesions larger than 3 cm are defined as masses. Solitary
pulmonary nodules are benign in 60–70% of cases.
Of course when a lung nodule is detected the first thing to do is trying to under-
stand whether this is benign or malignant. To do this, some parameters need to be
evaluated: the velocity of growth, the margins, the dimensions, and the presence of
cavitation and satellite nodules.
Benign lung tumors are not common, and the diagnosis often is histologically
made. They include hamartomas, papillomas, lipomas, neurofibromas, and endome-
triosis [17].

8.2.3.1 Velocity of Growth

Benign tumors usually grow in years, active granulomas in weeks, whereas malig-
nant nodules double their diameter in 2–18 months. We can say that a nodule has
doubled when its diameter is increased by 1.25 times. For these reasons, comparison
with precedent exams is essential during the evaluation of a pulmonary nodule [18].

8.2.3.2 Margins
The margin characteristics may give an indication of a nodule’s nature. Regular and
smooth margins are usually considered as suggestive of benign disease but in some
cases may be present also in malignant nodules. Irregular, ill-defined, lobulated and
spiculated margins are indicative of malignancy [21].

8.2.3.3 Dimensions and Cavitation

The dimensions of the nodule are helpful to predict malignancy. Nodules smaller
than 5 mm are almost always benign, when they are more than 7 mm, they are
malignant in 1% of cases, when less than 1 cm in 15%, and less than 2 cm in 40%.
Masses more than 5 cm have a 95% chance of malignancy [20, 28].
Cavitation may be present in both benign and malignant tumors. Figure 8.1
shows two examples of pulmonary masses.

8.2.3.4 Differential Diagnosis

Lung cancer needs of course to be distinguished from different thoracic pathologies
other than benign lung lesions such as mediastinal masses, metastases but also
benign conditions.
It is not always easy to differentiate between a parenchymal mass and a medias-
tinal one. Some parameters may be helpful in performing differential diagnosis such
as the location and the margins. A mass is usually located in the lung when it is
surrounded by pulmonary tissue in the frontal and lateral projections. On the con-
trary, a mediastinal mass usually has sharper margins and often compresses, dis-
places, or obstructs mediastinal structures.
Primary lung cancers should also be distinguished from metastases. In fact, the
lung is one of the most common sites of metastasis. The most common primary
tumors that metastasize in the lungs are breast cancer, renal cell carcinoma, colon
cancer, and seminoma.
180 Z. Falaschi et al.

Fig. 8.1 Two examples of large pulmonary masses in the inferior right lobe in P-A and L-L
projections

The lesion number can help us, in fact metastases are solitary only in a quarter of
cases. Metastases also have sharp margins and do not contain cavitation.
A bronchogenic cyst may also be mistaken for lung cancer. This congenital
defect is rare, and its location depends on the timing. It can be located in the medi-
astinum or intrapulmonary. On chest X-ray, it presents as a rounded opacity with
smooth margins, usually in the lower lobes and can be filled with air or fluid.

8.2.4 Atelectasis

Lung cancer may also present as an area of atelectasis. This is defined as a loss of
lung volume caused by the reduction in the content of air in the bronchi and in the
alveolar spaces. Lungs that normally appear black become white when fluids or soft
tissue substitutes air. So normally on the chest X-ray atelectasis appears as an
opaque area. In the early phases this may not present as an opacity, but indirect signs
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 181

can be visible and be suggestive of its presence, for example, the reduction in
lung volume.
Therefore in addition to the increased lung opacity, there are other signs. The first
one is the shift of the interlobar fissures toward the area of atelectasis. When this is
in the right and left upper lobes, both fissures move superiorly, as shown in Fig. 8.2.
When it is in the middle lobe the oblique one moves upward and the horizontal one
downward. If atelectasis is in the inferior lobes the oblique fissure moves downward
and posteriorly.
A second sign is the upward displacement of the hemidiaphragm which is usu-
ally more evident when atelectasis involves the inferior lobes. In addition to this, the
mobile mediastinal structures move toward the affected site. In case of upper lobes
atelectasis, there is a displacement of trachea and the superior mediastinum. Trachea,
which is normally in midline location, in correspondence with the spinous pro-
cesses of the vertebral bodies, may shift toward the area of volume loss. When
atelectasis involves the inferior lobes the heart and the inferior mediastinum usually
move. When the heart shifts toward the left, there is an overlap between the right
heart border and the spine. When it shifts toward right, the left heart border is almost
in the midline.
The hila may also dislocate: superiorly if there is atelectasis of the upper lobes,
downward if the inferior ones are affected. Of course it is important to remember
that the left hilum in the majority of the population is located superior to the
right one.
Another sign of atelectasis is the compensatory over inflation of the unaffected
ipsilateral lobes or the contralateral lung. The bigger the atelectatic area the more
evident the over inflation is.

Fig. 8.2 This is a patient

with lung cancer that
presents with atelectasis: a
parahilar opacity and an
upward movement of the
horizontal fissure
182 Z. Falaschi et al.

Of course there can be atelectasis of the whole lung and in this case the medias-
tinum is shifted toward the affected site so that the contralateral lung can cross the
midline.
Atelectasis needs to be differentiated from a non-atelectatic parenchymal con-
solidation. The absence of air bronchogram may help us in doing this. In fact this
does not occur in case of atelectasis because obstructed bronchi and bronchioles fill
with secretions and appear radiopaque on the X-ray.

8.2.4.1 Types of Atelectasis

There are different types of atelectasis, and lung cancer is associated mainly with
the obstructive and compressive ones.

Compressive Atelectasis
This type of atelectasis is caused by the passive compression of the lung that can be
caused by a large pleural effusion, a pneumothorax or a space-occupying lesion
such as a lung mass.

Obstructive Atelectasis
Obstructive atelectasis is caused by the absorption of air from the alveoli through
the capillary bed distal to an obstructive lesion of the bronchial tree. This leads to
the collapse of the affected segment or lobe, and since the pleurae remain in contact
with each other, there is a pull on the mobile structures of the thorax toward the area
of atelectasis. This can be caused by various etiologies such as bronchial carcinoma,
mucus, and foreign bodies.
There are also cicatrization and band atelectasis. The first occurs due to fibrotic
changes in the parenchyma caused by chronic inflammation that lead to lung vol-
ume reduction. The second presents as fine horizontal bands of atelectasis that
occurs when the patient has decreased diaphragm mobility.

8.2.5 Pleural Effusion

Single-sided pleural effusion should always raise the suspect of lung cancer, as
shown in Fig. 8.3. This is usually caused by the invasion of the pleural space by
malignant cells, which may both cause a reactive increase in the reactive production
of fluid and impair its reuptake by the pleura. Pleural effusion can be defined as an
excessive accumulation of fluid in the space between the visceral and parietal pleura.
The pleural space normally contains about 2–5 mL of fluid. This accumulates when
the equilibrium between fluid formation and resorption is altered. This is the most
common pleural finding documented on X-ray.
When the patient is in the upright position pleural fluid accumulates in the base
of the thoracic cavity and we can only see it if it exceeds 250 mL. When the exam
is performed in supine position, the fluid collects posteriorly and can demonstrate
effusions as small as 15–20 mL. The whole hemithorax is opacified when 2 L of
fluid is collected.
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 183

Fig. 8.3 This is an example of a patient with lung cancer that presents with pleural effusion

In some cases fluid may accumulate between the inferior surface of the lung and
the hemidiaphragm and may simulate an elevation of the diaphragm.
Lung tumors should not be confused with pseudotumors which are also called
vanishing tumors. These are fluid collections either between the layers of an inter-
lobar pulmonary fissure or beneath it. Of course these disappear when the underly-
ing condition is treated.
There are four types of pleural effusion: exudative, transudative, chylous, and
hematic. The first two are the most common ones and differ for the protein content.
Transudate contains less than 3 g/100 mL and occurs due to an increase in hydro-
static pressure or a decrease in oncotic pressure.
Exudate has more than 3 g/100 mL and is caused by an increased capillary per-
meability. The most common cause of exudative pleural effusion is malignancy.
Other causes are infections, abdominal diseases, thromboembolism, and tho-
racic trauma.
The chylous effusion contains triglycerides or cholesterol and may occur for
example due to the rupture of a great lymphatic vessel, whereas the hematic one
may be caused by lung laceration or breaking of a vessel.

8.3 Role of CT in the Diagnosis of Lung Cancer

in Older Patients

The most accurate technique nowadays in lung cancer detection and staging is CT
imaging thanks to its high spatial and contrast resolution. In particular, thanks to the
axial scan plane and the possibility of multiplanar reconstructions (MPR), it elimi-
nates the overlapping of the various structures, solving the greater limit of tradi-
tional chest radiography (CXR) [23].
184 Z. Falaschi et al.

Moreover, the introduction and the utilization of high-resolution CT (HRCT)

with thin sections has enabled radiologists to more accurately detect and determine
the imaging characteristics of lung lesions, guiding the patient toward more precise
therapeutic processes or further diagnostic exams (follow-up examinations, bioptic
exams, CT-PET, etc.) [24].
The administration of iodinated organ contrast medium helps the staging of the
disease, favoring the search for hilo-mediastinal adenopathies, metastases, and pos-
sible neoplastic embolisms [25].
Lung cancer can present as a nodule or a mass, two distinct entities based on a
purely dimensional criterion. A pulmonary nodule is defined as a small (up to
30 mm) and well-defined opacity completely surrounded by normally ventilated
lung parenchyma, while a mass is defined as an opacity measuring more than
30 mm, the latter is more likely to be neoplastic in nature [25].

8.3.1 Pulmonary Nodules

Pulmonary nodules are frequently found incidentally on chest CT exams performed

for unrelated reasons.
The role of the radiologist is to distinguish between benign lesions and lesions
with evolutionary characteristics, suggesting follow-up examinations or additional
invasive imaging techniques.
To meet this need in 2017 updated Fleischner Society guidelines have been pub-
lished to standardize the management of incidental pulmonary nodules and thereby
reduce the number of unnecessary follow-up exams in patients with more than
35 years not belonging to specific high-risk groups (immunocompromised, with
known primary cancers, etc.). As in these high-risk patients, treatment should be
individualized relying on the specific clinical situation [26].
These guidelines suggest that CT with image thickness of 1.0–1.5 mm is neces-
sary for the study, the characterization, and the correct measurement of pulmonary
nodules. For the detection of micronodules, the reconstructions on the sagittal and
coronal planes and the MIP (maximum intensity projections) images are very use-
ful. Furthermore, follow-up imaging should use a low-radiation technique (average
effective radiation dose 1.5 mSv) [24, 29].
These guidelines are based on risk stratifications of both patients and nodules. In
particular, nodules are classified as solid or subsolid, besides specifically subsolid
nodules can be subdivided into pure ground glass nodules (without solid compo-
nent) and part-solid nodules as shown in Fig. 8.4.
Indeed, the two main factors determining the risk of a nodular lesion to be malig-
nant are its size and morphology as shown in Tables 8.1 and 8.2.
Morphology refers specifically to attenuation characteristics (solid, part-solid, or
purely ground glass) and to the margins (smooth, lobulated, or spiculated) of
the nodule.
Size can be measured with a manual method based on the average of the long and
short axes, rounded to the nearest millimeter or with nodule volumetry.
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 185

a b c

Fig. 8.4 Nodule types: (a) Solid, (b) Part solid and (c) Pure ground glass (GGO)

Table 8.1 2017 Fleischner Society Guidelines for management of incidental solid nodularities
Nodule Risk
type factors <6 mm 6–8 mm >8 mm
Solitary Low No routine CT at 6–12 months Consider CT, CT-PET or
nodule risk follow-up (consider at tissue biopsy at 3 months
18–24 months)
Solitary High Consider CT at CT at 6–12 months and at Consider CT, CT-PET or
nodule risk 12 months 18–24 months tissue biopsy at 3 months
Multiple Low No routine CT at 3–6 months CT at 3–6 months
nodules risk follow-up (consider at (consider at
18–24 months) 18–24 months)
Multiple High Consider CT at CT at 3–6 months and at CT at 3–6 months and at
nodules risk 12 months 18–24 months 18–24 months

Table 8.2 2017 Fleischner Society Guidelines for management of incidental subsolid
nodularities
Nodule type <6 mm >6 mm
Solitary GGO No routine follow-up CT at 6–12 months. If stable, CT every
nodule 2 years for a total of 5 years
Solitary part No routine follow-up CT at 3–6 months. If stable, CT every year
solid nodule for 5 years
Multiple CT at 3–6 months. If stable, CT at 3–6 months. Subsequent management
nodules consider CT at 2 and 4 years based on the most suspicious nodule(s)

Other factors to be evaluated in the characterization of pulmonary nodules are:

–– Growth or stable size: A solid nodule that has been stable for 2 years or more on
CT does not need any further investigations. In contrast, subsolid nodules could
be attributable to a low-grade adenocarcinoma, which has slower growth average
and an elevated VDT (volume doubling time), so it is considered likely to be
benign only when stable for 5 or more years by CT.
186 Z. Falaschi et al.

–– Margins: Usually, benign nodules present themselves with well-defined and

smooth borders, while malignant lesions have spiculated or lobulated margins.
However, this is a sensitive but not specific criterion, as some lesions with spicu-
lated margins may nevertheless be benign. Furthermore, some malignant lesions,
such as metastases, often present with clear margins.
–– Fat and calcifications: The presence of fat density (between −30 and −150 HU)
within a smooth bordered nodule is suggestive for pulmonary hamartoma. There
are four patterns of calcification, which are central, diffuse, lamellated, and pop-
corn, that are mostly associated with granulomatous disease and hamartomas.
Nevertheless, calcifications may also be present in malignant nodules especially
if they are punctate or irregular.
–– Location: Lung cancer is more frequent in the upper lobes, especially on the
right side.
Perifissural or adjacent nodules to the pleural surface usually represent intrapul-
monary lymph nodes, especially if solid, homogeneous, and triangular-shaped. If
they comply with these characteristics, even if they are larger than 6 mm, they do
not require instrumental follow-up.
–– Numerosity: The multiplicity of nodules is generally associated with benign con-
ditions such as inflammatory diseases or granulomatous infections. The NELSON
trial demonstrated an increased risk of malignancy if the number of nodules is
between 1 and 4, if greater than 5 the risk is reduced [24].

8.3.2 Pulmonary Masses

The 2004 World Health Organization (WHO) classification divides lung cancers
into two main histological categories: non-SCLC (NSCLC, 85% of all lung cancers)
and small-cell lung carcinoma (SCLC, 15% of all lung cancers) [26, 30, 31].
The distinction between the various subtypes of lung cancer can help to evaluate
the subsequent diagnostic and therapeutic process and can give the clinician infor-
mation about a patient’s prognosis.
However, although some morphological and metabolic characteristics may sug-
gest the histotype of the detected lung cancer, the diagnosis of certainty is still his-
tological and requires biopsy sampling.

8.3.2.1 Non-Small-Cell Lung Carcinoma (NSCLC)

NSCLC includes three main histological subtypes: squamous cell carcinoma, ade-
nocarcinoma, and large-cell carcinoma.

–– Squamous cell carcinoma (SCC):

The term squamous refers to the flattened appearance of the neoplastic cells.
This aspect is due to the chronic inflammation that develops and causes squa-
mous metaplasia of the respiratory epithelium which then progresses into dys-
plasia and finally into a neoplastic lesion. From the histopathological point of
view, it can be divided into four subtypes: papillary, clear cell, small cell, and
basaloid.
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 187

SCC accounts for at least 20% of all bronchogenic cancers and is strongly
associated with cigarette smoking.
In two-thirds of cases SCC has central location with intraluminal obstruction
of the main, lobar, or segmental bronchus resulting in obstruction or atelectasis
of the downstream parenchyma. Centrally located tumors therefore manifest
themselves with symptoms such as chronic cough, superimposed infectious
pneumonia, or hemoptysis and are usually reachable by endobronchial examina-
tions. In the initial stages they therefore produce a thickening of the bronchial
wall, subsequently they can manifest themselves with hilar or peri-hilar masses
or they can be more subtle, manifesting mainly with indirect signs such as atel-
ectasis [28].
SCC can also have peripheral localization usually manifesting itself as a mass
with irregular borders. Peripheral cancer occurs later and is therefore diagnosed
when it is larger with possible involvement of the chest wall or when it is meta-
static. SCC is the most common histotype of Pancoast tumor, an example can be
seen in Fig. 8.5.
Another feature frequently associated with SCC is cavitation, both in the pri-
mary lesion and in metastases with irregular and thick margins. Figure 8.6 shows
an example of a big cavitated lesion, which has been proven to be a peripheral
SCC [30, 32–34].
–– Adenocarcinoma:
Histologically the term adenocarcinoma refers to an epithelial neoplasm with
glandular differentiation or intracytoplasmic mucin production.
Adenocarcinoma is the most common histologic type of lung cancer, account-
ing for nearly 40% of lung cancers. Furthermore, adenocarcinoma is also the
most common histologic group seen in women and nonsmokers, although there
is a minimal association with cigarette smoking.
In 2011, the International Association for the Study of Lung Cancer (IASLC),
American Thoracic Society (ATS), and European Respiratory Society (ERS)
introduced a new classification of adenocarcinoma, which is now divided into
four main categories: adenocarcinoma in situ (AIS), minimally invasive

a b

Fig. 8.5 (a) Axial CT scan of a 69-year-old man showing a Pancoast tumor in the right upper lobe.
(b) Coronal view of the same CT
188 Z. Falaschi et al.

a b

Fig. 8.6 (a) Axial CT scan of a 75-year-old man showing a cavitated mass in the right lower lobe.
Histological examination proved to be an SCC. (b) Coronal view of the same CT

adenocarcinoma (MIA), lepidic predominant nonmucinous adenocarcinoma,

and invasive mucinous adenocarcinoma [35].
Adenocarcinoma usually has peripheral localization; therefore, it is often pau-
cisymptomatic and of occasional occurrence if small in size.
Moreover, it presents as a solid, partially solid, or ground glass nodule (GGN)
or mass, and it may have well-defined, lobulated, irregular, or poorly defined
margins.
In particular, the ground glass appearance suggests a lepidic growth pattern
(growth of cancer cells along the alveoli without lymphovascular invasion),
while solid lesions usually present invasive patterns.
In fact, in literature thick spiculations, thickened bronchovascular bundles,
pleural retraction, concave notch and large size are reported as negative prognos-
tic factors. While ground glass components, bubble-like lucencies, air broncho-
grams, and small size are associated with a better prognosis.
Since the imaging spectrum of lung adenocarcinoma has a good correlation to
histologic findings AIS, MIA and lepidic predominant nonmucinous adenocarci-
noma manifest as lesions with predominant ground glass components.
Conversely, invasive mucinous adenocarcinoma usually presents as a lesion with
an important solid component [28, 36–39].
In Fig. 8.7 we can see a peripheral solid mass with lobulated margins, which
has been proven to be a case of adenocarcinoma.
–– Large-cell lung cancer (LCC):
LCC is an undifferentiated neoplasm that lacks any features of squamous,
glandular, and neuroendocrine differentiation in microscopy and immunohisto-
chemistry; its diagnosis needs resection specimens. LCC is characterized by
round/polygonal cells with large nucleoli and with a moderate amount of
cytoplasm.
LCC currently accounts for about 2%–3% of all cases of bronchogenic
carcinoma.
LCC is typically described as a large peripheral solid mass (usually >4 cm)
with irregular or spiculated margins. It is an aggressive tumor that often presents
focal necrosis, rapid growth, and early metastasis [28, 30, 39, 40].
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 189

Fig. 8.7 Axial CT scan of

an 82-year-old man
showing a peripheral mass
in the left lower lobe.
Histological examination
proved to be an
adenocarcinoma. Some
ground glass nodularities
concomitant in the
same lobe

8.3.2.2 Small-Cell Lung Carcinoma (SCLC)

SCLC is the third most common histologic type of lung cancer, accounting for
approximately 15% of all bronchogenic carcinomas. In particular, SCLC is the most
frequent primary pulmonary neuroendocrine neoplasm, and it is the histotype most
linked to cigarette smoking.
SCLC is more aggressive than non-SCLC and is characterized by rapid growth,
greater propensity for early development of widespread metastases (about 60%–70%
of patients at diagnosis), and thus by a worse prognosis (despite high response rates
to first-line chemotherapy, at least 80% develop recurrent or progressive dis-
ease) [31].
Over 90% of SCLCs are located centrally as they arise from the basal epithelium
in a lobar or main bronchi. The mass often presents with central necrosis or hemor-
rhagic foci, intralesional calcifications are also present in 20% of cases.
Administration of intravenous contrast medium can help to detect involvement of
mediastinal structures [41, 42].
SCLCs frequently manifest as large hilar or peri-hilar masses with mediastinal or
hilar lymphadenopathy (about 80%–90% of cases), as they rapidly involve regional
lymph nodes. Occasionally, SCLCs can present as coalescent mediastinal enlarged
lymph nodes without identification of the primary tumor, appearing similar to lym-
phoma [31, 42, 43].
Figure 8.8 shows an hilar mass indissociable from the bronchial branches and the
vessels for the right lower lobe and some enlarged mediastinal lymph nodes. The
mass has been proven to be an SCLC.
SCLCs are infiltrative tumors, in fact they often invade neighboring structures
such as main bronchi, causing atelectasis or post-obstructive pneumonia and the
pleura (about 40% of cases) causing effusion or thickening or pleural nodules.
Moreover, SCLC of the lung is the most common cause of SCVS (superior vena
cava syndrome), due to direct infiltration or compression/thrombosis.
190 Z. Falaschi et al.

a b

Fig. 8.8 (a) Axial CT scan of a 67-year-old man showing a peri-hilar mass in the right lower lobe.
Histological examination proved to be an SCLC. (b) The same CT after administration of contrast
medium that shows an indissociable mass from the bronchial branches and the vessels for the
lower lobe. The mass has a central necrotic component. Some enlarged lymph nodes in the medi-
astinal area may also be observed

In addition to symptoms due to thoracic involvement, SCLC is the most frequent

lung cancer associated with paraneoplastic syndromes, such as the syndrome of
inappropriate antidiuretic hormone secretion.

8.3.3 Lung Cancer Staging

8.3.3.1 TNM Classification

In this section, we are going to expose the eighth edition of the TNM in lung cancer,
which was issued by the international Association for the Study of Lung Cancer
(IASLC) in 2017 [28].

T Component
The T component can be classified into five categories, as shown in Table 8.3. The
tumor’s greater dimension is the main variable when assessing this parameter,
although the invasion of nearby anatomical structure plays a fundamental role. In
particular, the invasion of mediastinal structures such as trachea, carina, or pericar-
dium immediately leads to an increment of the T component. The infiltration of
peripheral tissues such as the pleura or the chest wall also comports a T increment.
If more than one neoplastic nodule is present, the location of such nodule respec-
tively to the main mass determines T staging.
IASLC recommends that all tumors are measured in centimeters and to use the
lung window in order to determine the greatest dimension, since using the medias-
tinal window can lead to an understaging.

N Component
Table 8.4 summarizes the N classification in the eighth edition of the TNM staging
in lung cancer. Lymph nodes with a short axis >1 cm are to be considered
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 191

Table 8.3 T stage definition in the 8th edition of the TNM in lung cancer
T: Primary tumor
Tx Primary tumor cannot be assessed or tumor proven by presence of malignant cells in
sputum or bronchial washings but not visualized by imaging or bronchoscopy
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor ≤3 cm in greatest dimension surrounded by lung or visceral pleura without
bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in
the main bronchus)
T1a Minimally invasive adenocarcinoma
(mi)
T1a Tumor ≤1 cm in greatest dimension
T1b Tumor >1 cm but ≤2 cm in greatest dimension
T1c Tumor >2 cm but ≤3 cm in greatest dimension
T2 Tumor >3 cm but ≤5 cm or tumor with any of the following features:
 – Involves main bronchus regardless of distance from the carina but without
involvement of the carina
 – Invades visceral pleura
 – Associated with atelectasis or obstructive pneumonitis that extends to the hilar
region, involving part or all of the lung
T2a Tumor >3 cm but ≤4 cm in greatest dimension
T2b Tumor >4 cm but ≤5 cm in greatest dimension
T3 Tumor >5 cm but ≤7 cm in greatest dimension or associated with separate tumor
nodule(s) in the same lobe as the primary tumor or directly invades any of the following
structures: Chest wall (including the parietal pleura and superior sulcus tumors), phrenic
nerve, parietal pericardium
T4 Tumor >7 cm in greatest dimension or associated with separate tumor nodule(s) in a
different ipsilateral lobe than that of the primary tumor or invades any of the following
structures: Diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal
nerve, esophagus, vertebral body, and carina
Source: Goldstraw et al., The IASLC Lung Cancer Staging Project: Proposals for Revision of the
TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung
Cancer. https://doi.org/10.1016/j.jtho.2015.09.009. PMID: 26762738

malignant. The N parameter is determined primarily by the pathological nodes loca-

tion. Direct extension of the primary tumor into a nodal station is considered patho-
logic nodal involvement.

M Component
Table 8.4 summarizes the M component. Nodules located in the pleura or in the
pericardium, as well as pleural or pericardial effusion and contralateral or bilateral
metastases in the lung parenchyma, are considered M1a. The M1b category identi-
fies a tumor with a single extrathoracic metastasis, while the M1c category encom-
passes tumors with multiple extrathoracic metastases.

8.3.3.2 Lung Cancer Stages

Tables 8.5 and 8.6 describe the lung cancer stage groups suggested by the latest
TNM edition, as well as the survival rates in different stages.
192 Z. Falaschi et al.

Table 8.4 N and M stage definitions in the eighth edition of the TNM in lung cancer
N: Regional lymph node involvement
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and
intrapulmonary nodes, including involvement by direct extension
N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral
scalene, or supraclavicular lymph node(s)
M: Distant metastasis
M0 No distant metastasis
M1 Distant metastasis present
M1a Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial
nodule(s) or malignant pleural or pericardial effusion
M1b Single extrathoracic metastasis
M1c Multiple extrathoracic metastases in one or more organs
Source: Goldstraw et al., The IASLC Lung Cancer Staging Project: Proposals for Revision of the
TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung
Cancer. https://doi.org/10.1016/j.jtho.2015.09.009. PMID: 26762738

Table 8.5 Correspondence between lung cancer stages and TNM categories

T/M Label N0 N1 N2 N3
T1a ≤ 1 IA1 IIB IIIA IIIB
T1 T1b > 1-2 IA2 IIB IIIA IIIB
T1c > 2-3 IA3 IIB IIIA IIIB
T2a Cent, Pl IB IIB IIIA IIIB
T2 T2 a > 3-4 IB IIB IIIA IIIB
T2b > 4-5 IIA IIB IIIA IIIB
T3 > 5-7 IIB IIIA IIIB IIIC
T3 T3 Inv IIB IIIA IIIB IIIC
T3 Saltell IIB IIIA IIIB IIIC
T4 > 7 IIIA IIIA IIIB IIIC
T4 T4 Inv IIIA IIIA IIIB IIIC
T4 Ipsi Nod IIIA IIIA IIIB IIIC
M1a Contr nod IVA IVA IVA IVA
M1a Pl dissem IVA IVA IVA IVA
M1
M1b Single IVA IVA IVA IVA
M1c Multi IVB IVB IVB IVB

Source: Detterbeck et al., The Eighth Edition Lung Cancer Stage Classification.
https://doi.org/10.1016/j.chest.2016.10.010
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 193

Table 8.6 Five-year survival rate for patients in different stages

Type IA1 IA2 IA3 IB IIA IIB IIIA IIIB IIIC IVA IVB
Clinical 92 83 77 68 60 53 36 26 13 10 0
Pathologic 90 85 80 73 65 56 41 24 12 – –
Source: Detterbeck et al., The Eighth Edition Lung Cancer Stage Classification. https://doi.
org/10.1016/j.chest.2016.10.010

Stage I: In this case the tumor is limited to the lungs and there is no nodal involvement.
Stage II: The neoplastic tissue is located in the lung and in the ipsilateral peribron-
chial or hilar nodes.
Stage III: The tumor is locally advanced and invades mediastinal nodes. In particular:
Stage IIIa: The neoplastic extension is only in ipsilateral mediastinal nodes.
Stage IIIb: The neoplastic extension is into contralateral mediastinal nodes or above
the clavicle.
Stage IV: The tumor is diffused into both lungs, to the pleural fluid or any other
body part [26].

8.4 Chest Characteristics in the Elderly Patient: Possible

Difficulties and Overlapping of Diagnoses

In a global perspective, the improvement of general life conditions and the develop-
ment of medical science have led to a stable increase in life expectancy worldwide.
Therefore, the age profile of the society is changing; due to the longer life of the
population and the combined reduction in fertility, we have seen a reduction of
people of working age and an increase in the proportion of the elderly population,
commonly referred to as people >65 years old, a phenomenon that is often referred
to as “demographic aging.” This trend, which first started in the richest countries in
the world, has involved all developing countries and is expected to continue in the
next couple of decades. These developments are likely to have profound implica-
tions, among others, in health and social care systems [44].
As we age, the human body is subjected to progressive decay due to physiologi-
cal metabolic, hormonal, and anatomical changes. The respiratory system and the
parenchymal, vascular, and osteo-cartilage structures that compose it are character-
ized by numerous physiological and pathological factors that determine a progres-
sive remodeling over the years. It is mandatory for the radiologist to know the most
important anatomical and physiological evolutionary characteristics of old age, first
of all of the chest, so as to be able to establish the real limit between changes in the
chest compatible with age and proper pathological pictures.
The constant aging of the general population, the condition of fragility and
greater predisposition to the disease associated with the aging of the body, the con-
stant improvement of the imaging technologies available to the radiologist, and the
194 Z. Falaschi et al.

increase in therapeutic options associated with greater expectations on the part of

the of the patient are all factors for which diagnostic imaging plays a primary role
in the elderly patient. The radiologist must know the main anatomical and physio-
logical evolutionary characteristics of the chest in the elderly patient, so as to be
able to establish the real limit between changes in the chest compatible with age and
properly pathological pictures.
The thorax as a whole can undergo changes that may affect the rib cage, the tho-
racic wall, the lung, and the mediastinum. Imaging techniques are now able to
objectify these changes, techniques that are an element of clarification for those
clinical pictures that are often vague or difficult to interpret. In general, it can be
said that traditional radiology, with the standard radiogram, is able to highlight most
of the typical aspects of the senile chest and that computed tomography highlights
them in a more analytical way by virtue of the advantages of reading the section
image [45].

8.4.1 Age-Related Rib Cage Deformation

The thoracic cage represents the anatomical structure responsible for carrying out
the function of “container” of the viscera of the thorax. It consists of the ribs, the
sternum, the dorsal spine, the diaphragm, and the muscles of the anterior and poste-
rior thoracic wall.
With aging, the skeleton of the rib cage undergoes a progressive stiffening, a
consequence of the calcification of the costal cartilages and the arthritic-­degenerative
processes affecting the costo-vertebral joints. These events, which are associated
with the progressive rarefaction of the bone matrix due to pathological condition
commonly present in the elder (i.e., osteoporosis) and the physiological reduction
of the tone of the parietal muscles, result in an increase in the fragility of the chest
wall, which results in a greater predisposition to fractures and deformation of the
bone components. Reduced thickness of intervertebral determinate worsening dor-
sal kyphosis and cause the onset of dorsal-lumbar scoliosis, which together with the
factors listed above determine deformation and reduction of compliance of the rib
cage. Other errors may be caused by frequent findings in the elderly such as rib
compact islands, vertebral osteophytic bridges, costo-transverse arthritic hypertro-
phy, all situations that can simulate parenchymal nodular opacity [46].
Even the involutional aspects affecting the muscle tissue are a source of interpre-
tation errors for the radiologist. In the elderly subject, there is a progressive replace-
ment of muscle cells with fat cells, resulting in the progressive atrophy of the
muscles of the chest wall. The atrophy of the muscle component, while not neces-
sarily altering the thickness of the chest wall, in any case determines a significant
alteration of the constitution. Such modifications may go unnoticed on a careful
physical examination, but are always apparent on the examination performed using
diagnostic imaging. On a standard chest radiographic examination, it is possible to
observe widespread radiolucency of the thoracic resulting in the lower radio-­
attenuating capacity of the adipose component. This finding becomes even more
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 195

evident with the aid of the tomographic examination (CT) which allows a better
definition through the acquisition of multiplanar sequences.

8.4.2 Mediastinum Deformation: Cardiomegaly, Aortic Ectasia

With aging, the cardiac organ undergoes various paraphysiological involutionary

events, concerning the pericardium, myocardium, coronary arteries, and valve sys-
tems. The set of these paraphysiological alterations constitutes a commonly defined
picture of the “senile heart.”
The main pathophysiological characteristic of this condition consists in the
imbalance that is created between the cardiac and respiratory pumps: the enlarged
heart occupies a large part of the chest (which, as already mentioned, is relatively
inexpensive), to the detriment of the lungs, so the respiratory excursions are reduced
with alterations of the perfusion dynamics, as well as ventilatory ones [47].
The pericardial tissue undergoes the physiological process of adipose involution
with an increase in the relative quantity of fat, more evident at the level of the
cardio-­phrenic angles which, consequently, present a greater “dullness” in the stan-
dard chest radiogram.
Furthermore, the volumetric increase in the heart chambers is appreciable, in
particular in the left atrial cavity and especially in the left ventricle, where there is a
significant increase in the ventricular myocardial mass, an aspect attributable to
cardiac remodeling consequent to the state of typical systemic hypertension in the
elderly patient (Fig. 8.9) [48].
The mediastinal image may appear enlarged as a whole or only in some points,
generally without gross deformations. The main elements to be analyzed are the
aorta, the trachea, and the heart. This aspect is accentuated with the patient’s supine
position (chest to bed) and can simulate an engagement of the superior mediasti-
num. Important elements to consider in order to exclude mediastinal pathology are
the preservation of the normal radiolucency of the tracheal belt and the preservation
of the normal thickness of the right paratracheal mediastinal line or “right

Fig. 8.9 Axial and coronal CT scan of a 83-year-old man with cardiomegalia. The volumetric
increase in the heart chambers is appreciable, in particular in the left ventricle
196 Z. Falaschi et al.

paratracheal band.” The frequent presence of catheters or tubes (CVC, SNG, PM

electrodes, etc.) can facilitate the interpretation of mediastinal anomalies, offering
important radiopaque landmarks [49].
These aspects are observable in the standard chest radiogram, appreciable as a
rounding of the lower left cardiac arch and, in the lateral-lateral projection, in the
protrusion by the cardiac shadow at the level of the clear retrocardiac space. In the
more advanced stages, the picture of the cardiac lung presents additional elements:
interstitial edema leads to the smoky appearance of the hila and vessels and leads to
the formation of Kerley’s striae, especially of type B. The trachea plays an impor-
tant role in the radiological judgment of the mediastinum superior. In addition to the
aspects previously analyzed, it can help in the evaluation of the hyper-transparency
of the lung of the elderly (which, as we have seen, may not be attributable to a
parenchymal pathology): for example, any “saber sheath” tracheal alteration can
address toward a correct diagnosis of pulmonary emphysema (Fig. 8.10).
Further alterations come from the formation of calcified plaques The coronary
arteries become twisted and are often home to calcific deposits and atherosclerotic
plaques; moreover, at the level of the valvular apparatus, they form calcific deposits,
especially at the level of the aortic valve and the mitral annulus. In these locations,
any calcifications of the valve flaps and fibrous rings must therefore be sought in the
radiogram, supplementing the study if necessary with a dynamic analysis of their
kinetic behavior in radioscopy. The main radiological aspects (RT and CT) are the
redistribution toward the apexes of the pulmonary pattern—“inverted distribu-
tion”—and a ratio of 1:1 between the caliber of the upper and lower vessels—
“balanced distribution” (expressions of the increase in venous pressure in the small
circle: 12–15 mmHg). The vessels generally become more tortuous and often
increase in caliber, also contributing to the so-called dirty lung appearance.

Fig. 8.10 Samples of standard chest radiograph in pulmonary emphysema with “saber sheath”
trachea. It represents degeneration and ossification of the tracheal cartilage due to elevated intra-
thoracic pressure
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 197

Radiologic imaging of the chest is also of primary importance in the detection of

aortic dilatation.
With increasing age, the aorta tends to acquire some characteristics that are
mainly represented by vessel elongation, dilatation, and the deposition of calcium in
the vessel walls. In particular, the aortic dilatation can represent a paraphysiological
variable related to the increasing age. With older age the elastic tissue of the vessel
walls can deteriorate and tends to be replaced with more rigid collagen tissue, lead-
ing to a dimensional increase in the diameter of the vessel. This dilatation can be
pathologic when it increases over a certain dimension, moreover, when the dilata-
tion is significant and reaches the appropriate measurement criteria, the term aortic
aneurysm is utilized. Age is one of the main risk factors for the development of
aortic aneurysm and for its subsequent rupture, leading to aortic dissection. Aortic
ectasia is better identified with spiral CT scan technique, which permits to study all
aorta districts, after the administration of contrast agent. However, it is possible to
identify aortic ectasia also with chest X-ray, especially if there are parietal calcifica-
tions, typically observed in the geriatric patient, which facilitate the identification of
the arterial profile (Fig. 8.11). In the evaluation of an aortic aneurysm, CT scan is
able to determine the extension, the evaluation of the dimension of the lumen and
the presence of thrombi [48].

8.4.3 COPD, Pneumonia

Chronic obstructive pulmonary diseases (COPD) essentially include, in the elderly,

asthma, the emphysema-chronic bronchitis complex, bronchiectasis, and chronic
inflammation of the small bronchi, and represent one of the main causes of morbid-
ity and mortality in the elderly patient.

Fig. 8.11 Aortic ectasia in the ascendant and aortic arch in an 88-year-old male, observed as a
prominent aortic knob
198 Z. Falaschi et al.

The findings of emphysema and chronic bronchitis in old age are the same as
those found in younger subjects, but more difficult to interpret correctly given the
frequent coexistence of alterations in other systems (cardiovascular, musculoskele-
tal) that can simulate them or mask the radiological manifestations. It is important
for the radiologist to know the pathophysiological basis of the pathologies of the
cardio-pulmonary circulation to avoid any misinterpretation of the image. For
example, a common mistake for the radiologist is to confuse the radiolucency of the
pulmonary fields resulting from the already described physiological involution of
the muscular structures for a picture of senile emphysema, in the absence of those
signs necessary to confirm a picture of hyperinsufflation, oligoemia, or of blisters
that must be present to confirm the diagnosis of emphysema [50].
Furthermore, in the elderly patients, the worsening of the pathological state is
often accompanied by nonspecific clinical manifestations such as asthenia, retroster-
nal pain, and deterioration of cognitive functions, thus leading to a late or inade-
quate diagnosis.
Both traditional radiology and computed tomography (CT) can provide an
important help in giving an initial diagnostic address to the appearance of the first
symptoms.
There are two classic radiological-clinical patterns that guide the physician in the
diagnosis of emphysema/chronic bronchitis in the elderly: the first pattern, arterial
deficiency, characterized by the rarefaction of the vascular pattern, corresponding to
the prevalence of the emphysematous picture; the second pattern, increased mark-
ings, sees the accentuation of vascular landmarks characteristic of the prevalence of
chronic bronchitis which is associated with secondary pulmonary arterial
hypertension.
Among the radiographic alterations observable in COPD reported in the litera-
ture and may concern alterations of the diaphragm (widening of the costo-phrenic
angles, lowering of the diaphragmatic dome, widening of the clear retrosternal
space), parenchymal (presence of emphysematous bubbles, thickening of the bron-
chial walls, areas of opacity), cardiovascular alterations (heart drop, dilation of the
pulmonary arteries with peripheral barrage), and alterations of the trachea (“saber
sheath” trachea).
The principle can be stated that, even in the presence of multiple concomitant
radiographic alterations, the standard X-ray is not very sensitive in the mild-­
moderate severity forms of COPD, it may also appear negative in patients with
chronic bronchitis, while it acquires greater usefulness in the most advanced forms,
although it is not possible to correctly quantify the extent or extent of functional or
anatomical damage. It is generally used in the presence of acute onset of symptoms
with fever to confirm the clinical suspicion of a bronchopneumonic outbreak, deter-
mining the presence of any complications, such as pleural effusion and bronchial
obstructions. Moreover, it is often technically inadequate since it is carried out in
nonoptimal conditions, with the patient in a semi-sitting position, insufficient inspi-
ration, with portable equipment, which further reduces its already limited diagnostic
value [51].
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 199

Finally, the chest X-ray can also detect, in asthmatic forms, nonspecific radio-
logical signs, such as thickening of the bronchial walls and bronchopneumonic foci,
or recognize the acute complications of an asthmatic event, such as pneumothorax
or pneumomediastinum.
CT is more useful in this regard, which allows us to quantify with sufficient pre-
cision the extent of emphysema in HRCT and the severity of emphysematous dam-
age even in the mildest forms; it is possible to demonstrate with HRCT the presence
of emphysema in patients with impaired respiratory function and completely nor-
mal chest radiograph. In the pattern, increased markings are often observed in
HRCT, in addition to the reduced parenchymal density, oligoemia, indicative of
emphysema, thickening of the bronchial and bronchiolar walls and areas of ground
glass opacity.
Finally, HRCT allows precise documentation of the type of prevailing
emphysema:

• Centrilobular emphysema, the most common type usually associated with smok-
ing, affects the centrilobular portion of the lung. Usually the upper lobes of the
lungs are affected.
• Panlobular emphysema, also called panacinar emphysema, can involve the
whole lung or mainly the lower lobes. Is commonly associated with alpha-1 anti-
trypsin deficiency (A1AD or AATD).
• Paraseptal emphysema, also called distal acinar emphysema, relates to emphy-
sematous change next to a pleural surface. The cystic spaces known as blebs or
bullae that form in paraseptal emphysema typically occur in just one layer
beneath the pleura (Fig. 8.12).

In the forms of severe chronic asthma, HRCT, much better than the thoracic
radiogram, is able to demonstrate and quantify the thickening of the bronchial walls
due to the structural remodeling of the walls and can detect the frequent presence of
bronchiolitis highlighting direct signs (branched opacities from commitment of the

a b c d

Fig. 8.12 Comparative images in axial computed tomography. (a) Absence of emphysema; (b)
Centrilobular emphysema; (c) Paraseptal emphysema; (d) Panlobular emphysema
200 Z. Falaschi et al.

bronchial lumen, parietal thickening of the bronchioles with bronchiectasis) or indi-

rect (expiratory air trapping) of anatomo-functional alteration of the small airways.
In elderly patients, however, the use of HRCT is often superfluous for a better
morphological definition and for an accurate balance of extension of the emphasis,
which in any case would have a limited therapeutic impact.

8.4.4 Pneumonia

Pneumonia represents the main causes of death from infection, especially in the
elderly population where the immune system is often compromised due to an age-­
related decrease in immune activity, chronic use of medications altering immune
function as the use of systemic corticosteroids in rheumatic disease.
Pneumonia can be divided into typical or atypical presentation, and in accor-
dance to history in community acquired, nosocomial, or infections in the
immunocompromised.
Conventional chest radiography plays a major role in diagnosing pneumonia,
being able to detect or exclude infiltrates, show the extent of the disease, estimate
possible complications, and show response to treatment. However, it is not indicated
in the suspicion of pneumonia in an immunocompromised patient, where the image
obtained is often normal.
Supported by clinical history and clinical laboratory data, chest radiography
allows to limit the spectrum of possible pathogens and will guide the calculated use
of antibiotics.
It is important to know the possible differential diagnoses in the presence of
certain signs, such as the presence of persistent infiltrations, which can lead to a
diagnosis of bronchoalveolar carcinoma. In the elderly patients, elimination of pul-
monary infiltration usually takes longer. It was shown that 15% of elderly patients
still showed radiographic abnormalities beyond 3 months. Delayed clearance may
be related to existing comorbidity. For this reason, a minimum interval of 3 months
for follow-up radiograph appears to be indicated to rule out previous malignant
changes.

8.4.5 Conclusion

In the elderly, conventionally defined as individuals >65 years of age, it is often dif-
ficult to establish what is normal, due to the numerous anatomical and physiological
changes that occur during the physiological process of aging. Knowing how to dis-
tinguish normal pictures from strictly pathological pictures is an important chal-
lenge for the radiologist today. Diagnostic imaging often offers borderline results to
chest imaging, and it is essential to know how to distinguish a picture that is only
apparently pathological from an image that may underlie the principle of pulmonary
pathologies for which the elderly patient, due to the condition of fragility associated
with aging, is particularly vulnerable.
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 201

8.5 Early Detection of Lung Cancer and Mortality Reduction

with Low-Dose CT (LDCT)

Lung cancer is currently the leading cause of cancer-related mortality worldwide.

Nevertheless, when diagnosed at the early stage (IA), it shows a survival rate of
75% at 5 years: it means that an early diagnosis is fundamental to reduce its mortal-
ity [52].
Low-dose CT (LDCT) is a low-dose radiation and rapid-execution imaging tech-
nique that has been largely studied as a screening method for lung cancer.
Two large randomized controlled trials of low-dose CT (LDCT)-based lung can-
cer screening in high-risk populations—the US National Lung Screening Trial
(NLST) and NELSON—have provided evidence of a statistically significant mor-
tality reduction in patients (20% for NLST, 24% in men and 33% in women for
NELSON) LDCT-based screening programs for individuals at a high risk of lung
cancer have already been implemented in the USA [53].
Following the US Preventive Services Task Force Recommendation Statement
(USPSTF) guidelines, the annual screening for lung cancer with LDCT is recom-
mended in adults aged 50–80 years who have a 20 pack-year smoking history and
currently smoke or have quit within the past 15 years. Screening should be discontin-
ued once a person has not smoked for 15 years or develops a health problem that
substantially limits life expectancy or the ability to undergo curative lung surgery [54].
To better select the population at risk for lung cancer, they have introduced some
risk-based prediction models (LLP and PLCO the most used) which include other
risk factors like asbestos exposition, family history, cancer history, concomitant
respiratory diseases, etc.
However, they yield modest additional life-years, increased overdiagnosis and
poor benefit-to-harm ratio because of predominantly selecting older individuals.
Efficient implementation of risk-based lung cancer screening requires careful con-
sideration of life expectancy for determining optimal individual stopping ages. For
example, in a recent study conducted in Germany as part of the German Lung
Cancer Screening Intervention trial on 4052 long-term smokers, no significant
reduction in lung cancer mortality was found among patients who underwent regu-
lar LDCTs. However, differential analyses by sex showed a significant reduction in
lung cancer deaths among the screened women [55].
Effective risk stratification and management of detected lung nodules are crucial
aspects for the success of any lung cancer screening programme. Many participants
have a lung nodule detected at baseline which needs to be distinguished from a lung
nodule developed within a known time frame.
Importantly, most lung nodules detected, either at baseline or thereafter, are small.
The assessment of nodule size has been based on the measurement of the longest
diameter. However, nodules are rarely perfectly shaped, thus whenever possible,
other means of size assessment such as volumetry estimation should be preferred.
Most nodules detected during lung cancer screening can be classified as low-risk
or intermediate-risk nodules, involving decisions on additional follow-up screens
(regular (1 year) or short-term (3 months)).
202 Z. Falaschi et al.

Regarding the screening frequency all countries recommend an annual screening

interval; however, the outcomes of the NELSON study suggest that a sex-specific
interval could be applied in the future because nodules tend to have a slower growth
rate in women than in men.
Furthermore, analyzing the results from the Multicentric Italian Lung Detection
(MILD) trial, it has been suggested that individuals with a negative baseline result
might benefit from undergoing biennial instead of annual screening.
The debate on screening frequency is still ongoing (Table 8.7).
Numerous cost-effectiveness analyses have been conducted, some of them lead-
ing to both annual and biennial screening programmes potentially cost-­effectiveness.
Goffin et al. compared both strategies in a scenario using the NLST eligibility crite-
ria, concluding that biennial screening used fewer resources and, although associ-
ated with lower gains of life-years, resulted in very similar quality-adjusted
life-years gains over a time frame of 20 years.
The USA experience has shown only a fraction (<5%) of individuals at high risk
of lung cancer who underwent through the screening programme, thus demonstrat-
ing the difficulties in the effective recruitment of participants in national screening
programmes even when they are provided by most major medical societies.
The main reasons for low adherence most probably lay on the emotional involve-
ment of the patient at high risk and on some limits of the method such as the high
rate of false-positives and consequently the overdiagnosis: the NLST trial consid-
ered only two possible outcomes: positive or negative, with a 24% rate of FP.
However, in the NELSON trial, which has implemented the nodule-management
protocols (introducing the “indeterminate” outcome) and risk-stratification algo-
rithms, the false-positive rate was only 1.2% and the referral rate only 2.1%.
Challenges in the recruitment of high-risk and hard-to-reach individuals remain
one of the major barriers to the implementation of lung cancer screening pro-
grammes. Even among the most efficient centers in terms of recruitment in ongoing
UK implementation projects, few have a participation rate of >50%.

Table 8.7 Follow-up recommendations based on lung cancer nodule risk

Risk category Lesions detected Recommendation
Intermediate to No baseline nodule; no new nodule at Consider prolonged
high risk of lung follow-up screening; solid baseline nodule screening interval of up to
cancer (<1%) <100 mm3 or <5 mm; new solid nodule 24 months
<30 mm3 or <4 mm
High risk of lung Solid baseline nodule 100–300 mm3 or Short-term follow-up
cancer (~3%) 5–10 mm; new solid nodule 30–200 mm3 or (3 months); if negative:
4–8 mm; growing solid nodule with VDT of Annual screening
400–600 days; subsolid nodule, baseline or
new, of any size
Very high risk of Solid baseline nodule >300 mm3 or >10 mm; Referral to MDT for
lung cancer new solid nodule >200 mm3 or >8 mm; work-up; if negative:
(>15%) growing solid nodule with VDT <400 days; Annual screening
subsolid nodule that is growing or has an
altered morphology
Source: Heuvelmans [56]. Appropriate screening intervals in low-dose CT lung cancer screening.
Translational lung cancer research, 7(3), 281–287
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 203

During the COVID-19 pandemic, clinicians have been forced to balance the risk
of delaying potentially necessary evaluation and management against the risks of
exposing patients to the virus in hospital settings, or exposing healthcare workers to
patients who may be asymptomatic carriers of the disease [57].
In this scenario, consensus statements were developed to guide clinicians man-
aging lung cancer screening programs and patients with lung nodules during the
COVID-19 pandemic, concluding that it is [58, 59] appropriate to defer enrollment
in lung cancer screening and modify the evaluation of lung nodules due to the added
risks from potential exposure. In particular more than 95% of the clinicians involved
in the “CHEST expert panel” agreed to delay the evaluation of pulmonary nodules
detected incidentally or by screening that have a low probability of cancer or are
likely to be an indolent cancer [58, 60–67].

8.6 Therapy Response Evaluation in Lung Cancer Imaging

8.6.1 Post Surgery Imaging

8.6.1.1 Introduction
Lung cancers which fit into stage I (cT1N0 and cT2N0) or stage II (cT1N1, cT2N1
and cT3N0) can be eligible for surgery. Patients with a Stage IIIA neoplasia (cT3N1
and cT1–3N2) have a low probability of disease eradication by surgery alone, but
they may be considered eligible after adjuvant therapy.
Up to 76% of lung cancer patients undergo some kind of surgery during their
treatment journey. The commonly performed thoracic intervention on patients with
lung cancer is the pulmonary resection. There are two main types of pulmonary
resection: anatomical and non-anatomical. Anatomical resections are those which
respect the scissures and/or the lung anatomical divisions, such as pneumonectomy,
lobectomy, segmentectomy, or segmental resection. Two lobes in the right lung can
also be removed in an upper lobectomy (excision of the upper and middle lobes) or
in a lower lobectomy (excision of the lower and middle lobes). On the contrary, non-­
anatomical resections, which are also called atypical, usually remove a wedge-­
shaped portion of the lung parenchyma without respecting the anatomical boundaries.
Each procedure is subject to distinct postoperative complications, both early and
delayed, which radiologists usually encounter in day-to-day practice.

8.6.1.2 Imaging Findings After Lung Resection

After the intervention the pleural space can be filled by air and/or fluid; one or more
air-fluid levels may be present. If the resection does not involve the whole lung the
pleural collection usually disappears in the following weeks-months, even if some
chronic fluid accumulation may persist. If a radical pneumonectomy is carried out
the affected hemithorax appears completely lucent in the X-rays performed imme-
diately after the surgery and the mediastinum is slightly shifted toward the operated
side. Fluid tends to gradually fill the pleural cavity in the days after surgery; com-
plete filling may take as long as 30 days. Figure 8.13 shows an example of the chest
204 Z. Falaschi et al.

a b

c d

Fig. 8.13 (a) Chest X-ray obtained the first day after left pneumonectomy. (b) Chest X-ray
obtained on the third day after the intervention in the same patient. (c, d) Postero-anterior and
latero-lateral projections on the eighth day after the pneumonectomy. The images display how the
left chest cavity is gradually filled with fluid and the mediastinum is shifted toward the oper-
ated side

cavity gradually filling with fluid. On the contrary, an increase in air component
may indicate the presence of a perforation or a bronchopleural fistula. After the first
month the residual lung tends to compensatory hyperinflation, while the mediastinal
structures become furtherly shifted toward the operated side.
When an anatomical or an atypical partial resection is performed, volume loss is
obviously expected. Pneumothorax may be present immediately after the surgery, as
shown in Fig. 8.14. Surgical clips may be visible in the intervention site, where
atelectasis or bleeding may also be found in the days after surgery. Muscle flaps are
often used in order to obstruct the bronchi and prevent pneumothorax after lobec-
tomy or pneumonectomy. Muscle tissue is commonly collected from the intercostal
and from the serratus anterior; bone tissue may be present in the flap if periosteal
tissue from the adjacent rib is included.
After the median longitudinal sternotomy, cerclage wires surrounding the sternal
body are visible. If a traditional thoracotomy was performed a rib transection will
be seen, while in case of an “en bloc” chest resection several consecutive ribs will
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 205

a b

Fig. 8.14 (a) Chest X-ray performed the first day after a superior right lobectomy. The right dia-
phragm is elevated, subcutaneous edema and apical right pneumothorax are present. There is a
basal drainage to collect pleural fluids and an apical drainage to collect air. (b) Chest X-ray per-
formed on the same patient 3 days after the intervention. Resolution of the pneumothorax, no
pleural effusion

be transected. Subcutaneous emphysema, seen as multiple parallel translucent lines

in the subcutaneous tissue, is commonly seen after the surgery and usually reduces
in subsequent radiographs.

8.6.1.3 Chest X-Ray

In the hours and days after the intervention, one or more chest radiographs are com-
monly performed in order to assess the position of lines and tubes in the patient’s
thorax cavity. More often than not these exams are performed in antero-posterior
supine projection.

8.6.1.4 Chest CT
Patients with stage I or II lung cancer who were treated primarily with surgery
should undergo a chest CT with intravenous contrast administration every 6 month
for 2–3 years after the intervention according to the National Comprehensive Cancer
Network (NCNN) guidelines. After that period of time, a noncontrast enhanced
low-dose CT should be performed every year. On the other hand, patients with stage
III lung cancer treated for curative and not palliative intent should undergo a con-
trast enhanced chest CT every 3–6 month for 3 years, followed by a contrast
enhanced CT every 6 months for the subsequent 2 years and finally by a noncontrast
enhanced low-dose CT performed annually.

8.6.1.5 Common Early Complications After Lung Cancer Resection

Bronchopleural Fistula: If the terminal airways are not correctly sealed after the
intervention, a bronchopleural fistula may occur. On imaging, this is demonstrated
by the postoperative pneumothorax failing to resolve or by the appearance of new
air in the pleural space. A direct connection between the airway and the pleural
206 Z. Falaschi et al.

space may be demonstrated on chest CT, but not in every case. This complication
often requires surgical intervention. Figure 8.15 shows an example of this
complication.
Pneumonia: Aspiration, poor pain control, and mechanical ventilation may lead
to pneumonia in the postoperative days. Radiological findings include ground glass
opacities, consolidations, or cavitation that may be both peribronchial or subpleu-
ral. Pleural effusion may be present; an empyema may form following surgical
contamination or preexisting infections. Pneumonectomy patients are the most
affected.
Adult respiratory distress syndrome (ARDS): From 2 to 15% of patients undergo-
ing thoracotomy develop a diffuse damage of the alveolar-capillary barrier resulting
in acute lung injury (ALI). Clinically, respiratory failure and decreased PaO2/FiO2
ratio may be present. Findings on chest X-ray are nonspecific and are similar to
those of typical pulmonary edema and pulmonary hemorrhage. On chest CT, the
typical pattern involves bilateral dishomogeneous pulmonary opacifications that
usually form a gravitational pattern, with lung consolidations in the most dependent
areas and ground glass opacities in the superior regions. Additionally, bronchial
dilatation in the ground glass areas and pulmonary cysts may be present. The prog-
nosis is poor, with mortality that can be as high as 50%.
Pulmonary edema: This complication is more common after pneumonectomy. It
is caused by augmented hydrostatic pressure and by altered alveolo-capillary bar-
rier. Pulmonary edema is more common in patients who underwent abundant peri-
operative fluid resuscitations or plasma transfusions; even patients who suffer from
arrhythmias are more affected. On chest X-ray common findings include interlobu-
lar septal thickening, Kerley B lines, and diffuse alveolar opacities. The most impor-
tant differential diagnoses include pneumonia and ARDS.
Hemothorax: A damage to pulmonary or systemic vasculature can lead to a pleu-
ral space hematoma in up to 1.3% of operated patients. On X-rays a rapidly increas-
ing pleural effusion may generate the suspicion of pleural hematoma and lead to
further investigations. On chest CT, the pleural collection demonstrates diffusely
high density values ranging from 40 to 90 Hounsfield units. A surgical reinterven-
tion to evacuate the collection is often needed.
Lung torsion: This is an infrequent complication with modern surgery tech-
niques. However, a pulmonary lobe can undergo a torsion in the setting of pleural
effusion and pneumothorax. The middle lobe is most commonly affected. On chest
radiographs, the lobe appears diffusely radiopaque and reduced in dimensions, and
also the lobar position can be unusual. On chest CT, the lobe appears diffusely
hyperdense because of atelectasis and venous congestion; the airways and the ves-
sels appear to be distorted and possibly occluded.
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 207

b c

Fig. 8.15 (a) Chest X ray obtained the first day after right inferior lobectomy shows a large right
pneumothorax. (b, c) The control X-ray obtained 30 days after the intervention shows how the
pneumothorax fails to resolve. This raised the suspicion of bronchopleural fistula, which was sub-
sequently confirmed via bronchoscopy

8.6.2 Response to Therapy Assessment: RECIST and iRECIST

8.6.2.1 Medical Therapy in Lung Cancer

In stage II and III lung cancer, adjuvant systemic chemotherapy can result in a 4 to
5% survival improvement at 5 years. In lower stages, the value of adjuvant therapy
is more controversial: it was proved to result in a worse outcome in patients with
208 Z. Falaschi et al.

stage IA disease, while a limited survival benefit was demonstrated in patients with
stage IB.
Neoadjuvant chemotherapy has not been so extensively evaluated; its use may
however be beneficial since downstaging can be achieved, resulting in a less exten-
sive resection.
Patients with locally advanced lung cancer (stage III) should undergo a contrast-­
enhanced total body CT to rule out distant metastases, followed by a PET/CT. A
contrast enhanced brain MRI should also be performed to exclude intracranial
localizations of the disease. Platinum based chemotherapy has proved to be effec-
tive in improving survival in stage III lung cancers, both in resectable and in unre-
sectable tumors. Targeted immunotherapy agents have proven useful in the treatment
of stage IV patients with specific mutations, such as EGFR and ALK. The role of
immunotherapeutic agents in patients with stage I, II, and III lung cancer has not yet
been evaluated properly, although several clinical trials are under way to assess the
feasibility of targeted treatment in both the adjuvant and the neoadjuvant settings.

8.6.2.2 RECIST 1.1

Response evaluation criteria in solid tumors (RECIST) were first developed and
published in 2000 but they have been extensively revised in 2009 when the updated
RECIST came out. The objective of RECIST 1.1 guidelines is to simplify, optimize,
and standardize the tumor burden response in solid tumors. Additionally, the guide-
lines give recommendations regarding the standard reporting in studies that utilize
tumor reduction as primary endpoint.
RECIST 1.1 criteria dive the neoplastic lesions into measurable and nonmeasur-
able. Measurable lesions are those with a minimum size of 10 mm when measured
with a CT scan or those with a minimum size of 20 mm when measured on chest
X-rays. All other lesions are considered non measurable, including smaller lesions
and truly unmeasurable lesions such as pleural effusion and neoplastic lymphangi-
tis. Malignant lymph nodes are considered pathologically enlarged and measurable
when their short axis assessed by CT scan is ≥15 mm. Only the short axis should be
noted down at diagnosis and follow-up.
The initial neoplastic disease should be evaluated, establishing an overall tumor
burden at baseline. In this occasion, the neoplastic disease localizations are to be
divided into target and nontarget lesions. If more than a measurable lesion is pres-
ent the radiologist should describe up to five target lesions, with a maximum of two
target lesions for every organ. All target lesions must be measurable, and they should
represent every involved organ; the choice of target lesions should take into account
both the dimensions and the reproducibility of the measurement. That is, if the larg-
est lesion does not lend itself to an accurate and reproducible dimensional assess-
ment, the next biggest lesion should be chosen. A pathological lymph node can be a
target lesion only if the short axis is ≥15 mm: only the short axis contributes to the
tumor burden. All other lesions including other pathological lymph nodes are to be
considered non target, but still correctly identified at baseline. The sum of all target
lesions must be calculated: the short axis should be used for lymph nodes and the
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 209

biggest diameter should be used for all the other target lesions. This parameter is
known as baseline sum diameters.
Target lesions response criteria:

• Complete response (CR): All target lesions are no longer visible, all pathological
lymph nodes have a short axis <10 mm.
• Partial response (PR): A minimum decrease of 30% in the overall diameter of
target lesions compared to the baseline sum diameters.
• Progressive disease (PD): An increase of the sum of the diameters of target lesion
equal or superior to 20%, or the presentation of one or more new lesions.
• Stable disease (SD): Insufficient diameter reduction or increase to qualify either
for PR or for PD.

Nontarget lesions response criteria:

• Complete response: all nontarget lesions are no longer visible, tumor markers
are normal.
• Non-CR/non-PD: At least one nontarget lesion is still present or tumor markers
levels are superior to the norm.
• Progressive disease: Categorical progression of preexisting nontarget lesions.

The response criteria of target and nontarget lesions are to be evaluated together,
identifying the best overall response as shown in Table 8.8. Figures 8.16 and 8.17
show two clinical examples of partial response and progressive disease, respectively.

8.6.2.3 iRECIST
In recent years a new category of antineoplastic drugs has been developed, and it
evolved into one of the most important in the treatment of aggressive tumors: immu-
nomodulators. These highly specific pharmaceuticals act on specific intracellular
pathways, such as CTLA 4, PD-1, and PD-L1, and agents active on those pathways
have been marketed since 2011. Neoplastic diseases commonly treated with these
agents include melanoma, bladder, kidney, lung, and head and neck cancers.

Table 8.8 Best overall response according to RECIST 1.1

Target lesions Nontarget lesions New lesions Overall response
CR CR No CR
CR Non-CR/non-PD No PR
CR Not evaluated No PR
PR Non-PD or incompletely evaluated No PR
SD Non-PD or incompletely evaluated No SD
Incompletely evaluated Non-PD No NE
PD Any Yes or no PD
Any PD Yes or no PD
Any Any Yes PD
CR complete response, PR partial response, SD stable disease, PD progressive disease, NE not
evaluable
210 Z. Falaschi et al.

Fig. 8.16 Consecutive CT scans in a 71-year-old male patients. The images in the upper row are
from the initial CT scan, while the lower pictures are from the follow-up CT scan obtained
3 months later, after 4 cycles of chemotherapy. The pulmonary mass shrinked from 8.7 to 6.1 cm;
the pathological node’s short axis reduced from 10 to 4 mm. This can be classified as partial
response

Patients treated with these drugs can be a challenge for the radiologists, since
immunomodulators can provoke an unusual pattern of response which resembles
progressive disease. This concept has been known as pseudoprogression. From a
histopathological point of view, the phenomenon of pseudoprogression seems to be
correlated to the immune response stimulated by the drugs. The neoplastic tissue
becomes infiltrated by T CD4+ and T CD8+ lymphocytes, and the inflammatory
response may be accompanied by edema and hemorrhage. All these alterations can
and often do result in a perceived increase of the tumoral mass, while the patient is
actually responding to the therapy.
Given this response pattern, RECIST 1.1 felt inadequate to evaluate the therapy
response in patients treated with immunomodulators, and new criteria had to be
8 Neoplastic Diseases of the Respiratory System in Geriatric Patients 211

Fig. 8.17 Consecutive CT scans in a 74-year-old male patients. The images in the upper row are
from the initial CT scan, while the lower pictures are from the follow-up CT scan obtained
9 months later, after chemotherapy treatment. A new lung nodule has appeared in the right lower
lobe and the pathological node in the aorto-pulmonary window’s short axis increased from 2.7 to
3.4 cm. This is progressive disease according to RECIST 1.1

developed by the RECIST working group itself. The new criteria, apart from adding
the prefix “i” in front of the previous response evaluation classes (e.g., iCR, iPR),
defined two new key concepts: unconfirmed progressive disease, iUPD, and con-
firmed progressive disease, iCPD.
iUPD is defined just like the progressive disease in RECIST 1.1, but it needs to
be confirmed with a subsequent imaging evaluation obtained from 4 to 8 weeks after
the first examination. The progression is confirmed only if there is a further incre-
ment of the previously reported lesions, or if there is dimensional expansion of
previously stable localizations. If the progression is not confirmed, but instead the
lesions show a volume decrease in comparison with baseline values compatible
with iCR, iPR, or iSD, the bar is reset. In this case, iUPD has to manifest again and
then to be confirmed in order to have a confirmed progressive disease (iCPD). As a
212 Z. Falaschi et al.

consequence iUPD can be assigned several times, as long as the progression is not
confirmed in the following assessment. The appearance of new lesions results in
iUPD, but the progression is confirmed only if other new lesions are present in the
confirmatory evaluation or if the new lesions show dimensional increase. If iUPD
was given only on the basis of target or nontarget lesions, then the progression of the
other category in the confirmatory scan also brings to iCPD.
The principles for assigning the best overall response are similar to those
described in RECIST 1.1, but the presence of iUPD makes things a little more intri-
cate. In general, the best overall response in iRECIST (iBOR) is the best response
to therapy recorded from the treatment start to its end, and all imaging evaluation
must be taken into account. The assignment of an iUPD category will not nullify the
following iBOR of iCR, IPR or iSD, as long as the requirements for iCPD are not
met. A complete list of examples can be found in the iRECIST presentation article
in the bibliography [51, 52, 68–77].

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The Gastrointestinal System in Geriatric
Patients 9
Damiano Caruso, Domenico De Santis,
Francesco Pucciarelli, and Andrea Laghi

9.1 Introduction

All organs and physiological processes of the human organism, including gastroin-
testinal system, are affected by aging [1]. Effect of aging of gastrointestinal system
includes a reduction in sensory perceptions, salivation, oral health, the absorption of
nutrients, and lactose tolerance. Although many of these age-related changes are
primarily functional, there are other changes that can be detected with imaging tech-
niques (e.g., pancreatic atrophy, lobulation, and fatty degeneration [2]). Functional
changes can then result in organic alterations and therefore become visible by imag-
ing, both directly and indirectly [3]. In this type of patient, diagnostic imaging
acquires an increasingly important value, and constant technological innovations
allow for a more accurate and early diagnosis.
One of the main problems of geriatric imaging is that patients might have multiple
comorbidities, making it difficult for them to collaborate during the examination [4].
In fact, from the simplest of exams (such as X-ray) up to technically more complex
examinations (such as MR-cholangiography), patient collaboration is a fundamental
requirement in order to reduce artifacts and achieve reliable diagnostic quality.
This chapter will be focused on the main pathologies and problems related to the
imaging of the elderly and the main strategies to solve them will be illustrated in the
following paragraphs.

D. Caruso · D. De Santis · F. Pucciarelli · A. Laghi (*)

Radiology Unit, Department of Medical Surgical Sciences and Translational Medicine,
Sant’Andrea University Hospital, Sapienza—University of Rome, Rome, Italy
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 217
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_9
218 D. Caruso et al.

9.2 Esophagus

9.2.1 Achalasia

Achalasia is an esophageal motility disorder characterized by the absence of pri-

mary peristalsis and impaired lower esophageal sphincter (LES) relaxation [5].
Achalasia can be primary (idiopathic) or secondary (pseudoachalasia), caused by
malignant tumor at the gastroesophageal junction (GEJ) or, less commonly, by
benign conditions such as Chagas’ disease [6]. Achalasia is most frequently seen in
middle and late adulthood with no gender predilection. Dysphagia is the main
symptom, diagnosis is based on clinical findings and esophageal manometry [7].

9.2.1.1 Imaging Findings

Barium studies show a dilated non-peristaltic esophagus with smooth, tapered, sym-
metrical narrowing (“bird-beak narrowing”) at the GEJ [6]. Computed tomography
(CT) is useful for the evaluation of common complications (such as pneumomedi-
astinum or pneumopericardium subsequent to esophageal perforation, either iatro-
genic or not; aspiration pneumonia, and esophageal carcinoma) and for the
evaluation of causes of secondary achalasia, such as the infiltration of esophageal
plex by a pancreatic neoplasm [8, 9] (Figs. 9.1 and 9.2).

9.2.2 Hiatal Hernia

Hiatal hernia is a condition in which elements of the abdominal cavity herniates through
the esophageal hiatus into the mediastinum; prevalence of hiatal hernia increases with
age, with a slight female predilection. The organ most commonly involved is the stom-
ach, and the most comprehensive classification of hiatal hernias divides them into four
types: sliding (type I, the most common, >90%) and paraesophageal (type II, III, and
IV). In sliding hernia, the GEJ is usually displaced >2 cm above the esophageal hiatus,
due to a widening of hiatus itself. In paraesophageal hernia, the GEJ remains in its

a b

Fig. 9.1 Axial unenhanced CT (a) and portal venous phase (b) CT images of an 87-year-old
woman with achalasia depicts a dilated and thin-walled esophagus containing air-fluid level
9 The Gastrointestinal System in Geriatric Patients 219

a b c

Fig. 9.2 Coronal (a) and sagittal reformatted (b and c) portal venous phase CT images of the same
patient showing marked dilation of the entire esophagus, characterized by thin-wall and containing
endoluminal air-fluid level

normal location while the fundus of the stomach herniates above the diaphragm through
a defect in the phrenoesophageal membrane. Mixed hernias have also been described
(type III), which simultaneously include components of type I and II. Type IV consists
of mixed type with the association of herniation of other abdominal viscera. Hiatal
hernia may be asymptomatic or cause nonspecific symptoms, such as chest pain or
epigastric pain, nausea, and vomiting [10].

9.2.2.1 Imaging Findings

Chest X-ray is usually the imaging modality of first choice, especially in patients
complaining chest pain. On standard chest X-ray typical sign is retrocardiac opacity
with gas-fluid level. Contrast radiography under fluoroscopy is a useful modality for
the identification of hiatal hernias, but it has some limitations in their classification
(Fig. 9.3). The mobility of GEJ makes the “2 cm-rule” limiting, due to the esophagus
shortening during swallowing of barium, which makes the measurement unreliable.
CT accurately identifies and classifies thoracic hernias, revealing a potential loss
of integrity of the diaphragm, as well as the content of the hernia sac, especially
using multiplanar reformatted images. CT imaging is also useful in the identifica-
tion of compliances such as intestinal obstruction, highlighting dilated bowel tracts
with air-fluid levels both in thorax and abdomen, and in the exclusion of other path-
ological conditions mimicking radiographic findings of hiatal hernia, such as epi-
phrenic esophageal diverticulum, retrocardiac lung abscess with concomitant air
bubbles, and gastric pull-up surgery performed for esophageal tumors.
Ultrasound (US) and magnetic resonance (MRI) play a minor role. In particular
transthoracic or transabdominal US examinations have some limitations due to gas-­
filled intrathoracic intestinal loops, aerated lungs, and acoustic shadowing from the
ribs; this imaging modality is mostly used in pediatric cases. However, US can
detect the hernia site and the integrity of diaphragm. The use of Echo Color Doppler
(ECD) is helpful to directly visualize the vasculature of herniated organs [11]. Real-­
time MRI uses high spatiotemporal resolution sequences able to assess the dynamic
220 D. Caruso et al.

a b

Fig. 9.3 Chest X-ray in posterior-anterior (a) and lateral view (b) of a 73-year-old woman with
chest pain and dysphagia; a fluid-air level is present (arrows)

a c

Fig. 9.4 MRI axial T2-weighted image without oral contrast (a), and axial and coronal
T2-weighted images acquired after ingestion of oral contrast medium (b and c) of a 73-year-old
woman with chest pain and dysphagia. A voluminous sliding hiatal hernia is confirmed

physiological process of swallowing but currently is not routinely performed. A

recent study suggests the use of real-time MRI in patients with equivocal endo-
scopic results, preoperative assessment, and detection of surgical complications
after fundoplication (Fig. 9.4) [12].
9 The Gastrointestinal System in Geriatric Patients 221

9.2.3 Ulcers

Esophageal ulcers are the complication of inflammatory pathologies affecting the

esophagus. Common causes of esophagitis could be noninfectious (gastroesopha-
geal reflux disease (GERD), post-actinic, drug-induced disease, etc.) or infectious
(HIV, candida, etc.) [13]. GERD is very common in elderly individuals, with a prev-
alence of 14–20% [14].

9.2.3.1 Imaging Findings

Although endoscopy is the reference standard for evaluating esophageal mucosal
pathology, radiology also plays an important role [13]. Superficial ulcers and ero-
sions associated with reflux esophagitis can be seen on double-contrast studies such
as tiny collections of barium at or near the gastroesophageal junction [13]. A minor
role is played by CT, which is less sensitive and nonspecific [15].

9.2.4 Esophageal Cancer

Esophageal cancer is an uncommon cause of cancers, and its incidence increases

rapidly after the age of 40 years; mortality of esophageal cancer before the age of
45 years is also relatively low and increases rapidly after the age of 50 years, peak-
ing between the ages of 80 and 85 years [16]. The most common type of esophageal
cancer is squamous cell carcinoma (81–90%), followed by adenocarcinoma
(4–19%); alcohol, smoking, and Barret esophagus are some of the most common
predisposing factors [17]. Clinical presentation is often nonspecific (dysphagia is
one of the most frequent symptoms), and further symptoms may be related to both
locoregional and distant disease dissemination.

9.2.4.1 Imaging Findings

Imaging methods are especially useful for disease staging, as the reference standard
for diagnosis is endoscopy. Chest X-ray may show mostly indirect signs (irregulari-
ties of the esophageal lumen, signs of compression of the lesion, etc.).
CT not only allows the identification of signs related to the primary lesion,
such as eccentric or circumferential wall thickening, but is also able to accurately
assess locoregional dissemination (such as peri-esophageal soft tissue and fat
stranding, tracheobronchial or aortic invasion) and the presence of distant metas-
tases [17] (Fig. 9.5).
222 D. Caruso et al.

a b

Fig. 9.5 Axial (a) and coronal (b) portal venous phase CT images of a 71-year-old man with distal
esophagus cancer, showing circumferential irregular wall thickening (>5 mm; arrows)

9.3 Stomach and Duodenum

9.3.1 Peptic Ulcers

Peptic ulcers are the consequence of increased gastric acid secretion. Helicobacter
pylori infection is the main cause of peptic ulcers, although other etiologies have
been also recognized, such as stress and the use of nonsteroidal anti-inflammatory
drugs and corticosteroids [18]. Although its incidence is showing a trend of decrease,
peptic ulcer disease still represent a global problem, with a lifetime risk of develop-
ment ranging from 5% to 10% [19]. Duodenal ulcers are four times more common
than gastric ulcers; affected patients are often asymptomatic or present with nonspe-
cific symptoms (epigastric pain, nausea, etc.) or with signs and symptoms related to
complications (bleeding, perforation, etc.) [18].

9.3.1.1 Imaging Findings

The reference standard for diagnosis is gastroscopy; however, imaging is crucial for
the assessment of complications. Gastric and duodenal peptic ulcers have similar
features on double-contrast barium upper GI series, appearing as radiopaque out-
pouchings of the bowel wall when barium fills the ulcer crater [20]. CT plays a role
in the detection of complications, in particular it can detect signs of perforation
(pneumoperitoneum) and bleeding [21].

9.3.2 Duodenal Diverticulum

Duodenal diverticula are outpouching from the duodenal wall. They are usually
located near the ampulla of Vater and often asymptomatic. If present, symptoms
9 The Gastrointestinal System in Geriatric Patients 223

are related to complications such as hemorrhage, inflammation (diverticulitis),

jaundice, cholangitis, or perforation [22]. The presence of symptoms is correlated
to the size of the diverticula: large diverticula might cause relatively high pressure
upon the distal part of the common bile duct, reducing its caliber and causing
functional bile stasis or reflux of duodenal content, including bacterial agents,
which can ultimately lead to cholangitis, gallstones formation, and chronic pan-
creatitis [23, 24].

9.3.2.1 Imaging Findings

CT is the imaging technique of choice in the diagnosis of diverticula and their com-
plications. Diverticula are identifiable as saccular outpouchings arising from the
duodenum that may contain gas, fluid, contrast, food debris, or any combination of
these. They often contain a gas-fluid or gas-contrast level [25].
MR cholangiography (MRC) can also evaluate the relationship between diver-
ticula and the common bile duct. Highly T2-weighted sequences are crucial to
detect high signal intensity structures, such as biliary fluid content. Small-sized
duodenal diverticula can be overlooked, while the large ones are usually easily
detected due to their fluid content [24].

9.3.3 Gastric and Duodenal Cancer

Gastric cancer is the fifth most commonly diagnosed cancer in the world, and the
seventh most prevalent [26]; the cumulative risk of developing gastric cancer from
birth to 74 years of age is 1.87% in males and 0.79% in females worldwide. The
most common gastric malignancy is adenocarcinoma (95% of malignant tumors of
the stomach); there is a strong association with Helicobacter pylori infection; and
other risk factors are represented by smoking, pernicious anemia, anthropic gastri-
tis, and adenomatous polyposis [27].

9.3.3.1 Imaging Findings

CT is the staging imaging modality of choice, capable of diagnosing primary
tumor, assessing the locoregional spread, and detecting nodal involvement and
distant metastases [28] (Figs. 9.6 and 9.7). Lesion detection is facilitated by inges-
tion of negative contrast agents (water or gas); typical findings depend on the
morphology of lesions and includes a polypoid mass with or without ulceration,
focal wall thickening with mucosal irregularity, or focal infiltration of the wall
and ulcerations. Infiltrating carcinoma is typically characterized by wall thicken-
ing and loss of normal rugal fold pattern [29]. Comparable findings are found in
duodenal cancer [30].
224 D. Caruso et al.

a c

Fig. 9.6 Axial (a, b) and coronal (c) portal venous phase CT images of a 79-year-old man with
duodenal cancer. Note the diffuse duodenal wall thickening (arrows) causing dilation of the main
biliary duct (asterisk) and the intrahepatic biliary tree (arrowhead)

a c

Fig. 9.7 Axial (a, b) and coronal (c) portal venous phase CT images of a 72-year-old woman with
gastric cancer demonstrates extensive, circumferential, and irregular gastric wall thickening
(arrow) and enlarged nodes in the lesser sac (arrowhead)
9 The Gastrointestinal System in Geriatric Patients 225

9.4 Small Bowel

9.4.1 Small Bowel Cancer

Primary neoplasms of the small bowel are rare, 60% of these tumors are malignant.
Peak incidence occurs in the fifth and sixth decades, clinical manifestations are
nonspecific and can include nausea, vomiting, abdominal pain, weight loss, and
melena [31].

9.4.1.1 Imaging Findings

Small bowel imaging is challenging due to motion artifacts caused by bowel peri-
stalsis and respiratory motion. Due to widespread availability and high diagnostic
accuracy, CT and MR have become the imaging methods of choice for the assess-
ment of the small bowel. CT enterography and MR enterography, characterized by
oral ingestion of contras medium, provide excellent evaluation of small bowel
tumors [32]. Furthermore, these techniques are also capable to identify peritoneal
disease involvement (peritoneal carcinomatosis). Benign tumors can be directly
visualized as well-circumscribed masses with smooth margins growing within the
bowel lumen, their complications are represented by obstruction, intussusception,
or bleeding. Malignant lesions are characterized by irregular margins and invasive
locoregional growth; among malignant types, carcinoids are characterized by
increased serotonin production, invasive growth, and pronounced perifocal fibrotic
reaction (desmoplastic reaction). Typical imaging findings include muscularis pro-
pria thickening, puckering, wall retraction, serosal invasion, and mesenteric
metastases.

9.5 Large Bowel

9.5.1 Colonic Diverticulosis

Colonic diverticulosis is a disease characterized by the presence of multiple diver-

ticula; they are usually located at the mesenteric side of the colonic lumen, espe-
cially in the sigmoid colon and, to a lesser extent, in the descending colon, with a
size range from a few millimeters to few centimeters [33, 34]. Chronic constipation
is considered to be the main risk factor. Disease prevalence increases substantially
with age, up to 50–66% in patients older than age 80 years. Diverticula are usually
asymptomatic; when present, symptoms are related to complications like inflamma-
tion (diverticulitis) and perforation [35].

9.5.1.1 Imaging Findings

The imaging modality of choice in the assessment of colonic diverticula is CT,
allowing precise evaluation of diverticula number, size, and location. CT is also able
to identify complications and related inflammatory changes [36]. Imaging finding
of inflammation include pericolic stranding, often disproportionately prominent
226 D. Caruso et al.

a b

c d

Fig. 9.8 Axial unenhanced phase (a), axial (b, c), and coronal reformatted (d) portal venous phase
CT images of a 66-year-old man with acute diverticulitis, complicated with perforation. Note the
pericolic stranding (arrowheads) and the segmental bowel wall thickening (arrows). Perforation is
demonstrated by the presence of extra-intestinal air bubbles (asterisks)

compared to the amount of bowel wall thickening, segmental thickening, and

colonic wall enhancement (Fig. 9.8). The latter is usually characterized by inner and
outer high-attenuation layers with a thick middle layer of low attenuation.
Complications include perforation, abscess formation (seen in up to 30% of cases)
and fistulization (usually a long-term complication) [34].

9.5.2 Polyps

Polyps are wall protrusions and can be sessile or pedunculated. Mostly asymptom-
atic, they can cause symptoms in case of malignant transformation or in case of
excessive growth [37].

9.5.2.1 Imaging Findings

Reference Standard for Diagnosis Is Represented by Colonoscopy; However, CT
Colonography Is Playing an Increasing Role in Polyp Detection [38]

9.5.3 Colorectal Cancer

Colorectal cancer (CRC) is the third deadliest and fourth most commonly diagnosed
cancer in the world [39]. Incidence of CRC is expected to rise worldwide, since the
9 The Gastrointestinal System in Geriatric Patients 227

risk of developing CRC increases with age, and most countries have an ever-­growing
aging population [40]. Adenocarcinoma is the most common type (98%) and, in the
vast majority of cases, arises from pre-existing colonic adenomas (neoplastic pol-
yps), which progressively undergo a malignant transformation [41].
CRC is usually asymptomatic at early stages, eventually causing symptoms due
to excessive growth or complications (bleeding, perforation, and obstruction).

9.5.3.1 Imaging Findings

Although endoscopy is the reference standard for diagnosis, CT is the staging
modality of choice due to its ability in diagnosing primary tumor, assessing the local
spread, and detecting nodal involvement and distant metastases [42]. Most colorec-
tal cancers are identifiable as soft tissue masses with irregular margins narrowing
the bowel lumen; ulcerations are common in larger masses (Fig. 9.9). Occasionally
low-density masses with low-density lymph nodes are seen in mucinous adenocar-
cinomas, due to most of the tumor being composed of extracellular mucin; psam-
momatous calcifications in mucinous adenocarcinoma can also be present.
Complications include fistulae, obstruction, intussusception, and perforation.
Extracolic spread is also suggested by loss of fat planes between the colon and adja-
cent organs. Liver is the predominant organ to be involved in case of metastatic
dissemination. With CT, hepatic metastases usually appear as inhomogeneous
hypoattenuating masses, best visualized in portal venous phase. Other common
sites of metastases from colon cancer include the lungs, adrenal glands, and
bones [42].

a c

Fig. 9.9 Axial (a, b) and reformatted coronal (c) portal venous phase CT images of a 78-year-old
man with adenocarcinoma of the ascending colon. Note the irregular wall thickening with adjacent
fat stranding (arrows) and enlarged locoregional nodes (arrowhead)
228 D. Caruso et al.

9.6 Abdominal Emergencies in Geriatric Patients

Abdominal pain is a common cause of access to emergency, hospitalization, and

surgery among older patients. Elderly people are more often susceptible to compli-
cations compared to a younger patient for the same disease, due to their fragility, the
atypical disease presentations, the delays in care seeking, and the presence of
comorbidities; as a consequence, they generally have a worse prognosis [43].

9.6.1 Acute Cholecystitis

Biliary tract disease, specifically acute cholecystitis (AC), is a frequent abdominal

emergency in elderly patients. The clinical presentation is usually atypical, with
right upper abdominal quadrant pain without fever, nausea, or vomiting.

9.6.1.1 Imaging Findings

US is considered the diagnostic modality of choice in the initial diagnosis of
AC. Typical findings are the presence of cholelithiasis in combination with the
sonographic Murphy sign. Both gallbladder wall thickening (>3 mm) and pericho-
lecystic fluid are secondary findings. The atypical clinical presentation and the high
incidences of comorbidities and associated complications (perforation, cholangitis,
and emphysematous cholecystitis) make relevant the use of CT [44]. CT and MRI
findings include the identification gallstones, thickened gallbladder wall, perichole-
cystic fluid collections, and subserosal edema (Figs. 9.10 and 9.11).

9.6.2 Acute Appendicitis

Acute appendicitis refers to inflammation of the appendix. The classical presenta-

tion consists of periumbilical pain (referred) which within a day or later shifts to
McBurney point, with associated fever, nausea, and vomiting. Although it is a
pathology most commonly seen on the second to third decades of life, older patients
[45] generally has an atypical presentation, without fever and with late onset of
symptoms; abdominal pain is usually generalized.

9.6.2.1 Imaging Findings

US findings supportive of the diagnosis of appendicitis include: aperistaltic, non-
compressible, dilated appendix (>6 mm outer diameter), hyperechoic appendicolith
with posterior acoustic shadowing, distinct appendiceal wall layers, periappendi-
ceal fluid, and periappendiceal reactive nodal prominence/enlargement [46].
A contrast-enhanced CT should be performed in order to get to a tempestive
diagnosis: due to its highly sensitivity (94–98%) and specificity (up to 97%) for the
diagnosis of acute appendicitis; additionally, CT allows for alternative causes of
abdominal pain to be ruled out [47]. Typical CT findings include appendiceal
9 The Gastrointestinal System in Geriatric Patients 229

a b

Fig. 9.10 Axial unenhanced CT (a), axial (b), and coronal (c) portal venous phase CT of a
73-year-old man with acute cholecystitis. Note the thickened and enhancing gallbladder wall sur-
rounded by fluid and adjacent fat stranding (arrows). Unenhanced CT depicts also hyperdense
gallbladder stones in the infundibulum (arrowhead)

dilatation (>6 mm diameter), wall thickening (>3 mm), periappendiceal inflamma-

tion (fat stranding, thickening of the lateroconal fascia, mesoappendix extraluminal
fluid phlegmon, and abscess) [48].

9.6.3 Bowel Obstruction

Surgical adhesions and hernias are the main causes of small bowel obstruction,
while malignancy is the most frequent cause of large bowel obstruction.

9.6.3.1 Imaging Findings

A plain radiograph is the first imaging modality usually performed when a small or
large bowel obstruction is suspected. It can show bowel distention, air-fluid levels,
and a reduced bowel air in the segment downstream the obstruction. CT examina-
tion can nearly always detect the point of obstruction and its cause (Fig. 9.12). The
addiction of water-soluble contrast can be helpful in distinguishing complete from
incomplete small bowel obstruction [49].
230 D. Caruso et al.

a b

Fig. 9.11 Axial T2-weighted (a, b) and T2-weighted fat saturated (c) MR images of a 73-year-old
man with acute cholecystitis. MR images confirm the presence of gallstones in the gallbladder
infundibulum and show dilation of in the main biliary duct (arrows)

a b c

Fig. 9.12 CT scout image (a), coronal (b), and axial (c and d) portal venous phase CT images of
a 79-year-old man with volvulus. Note the “whirlpool sign” (arrows) and the dilated proximal
bowel loops filled with air
9 The Gastrointestinal System in Geriatric Patients 231

9.6.4 Acute Pancreatitis

Acute pancreatitis is an acute inflammation of the pancreatic gland, mostly caused

by gallstones, characterized by abdominal pain, usually radiating to the back, nau-
sea, vomiting, and high level of serum amylase. The risk of necrotizing pancreatitis
is significantly higher in patients older than 80 years [50].

9.6.4.1 Imaging Findings

Although diagnosis is based mainly on clinical data, imaging plays an important
role. In particular CT typical findings include focal or diffuse parenchymal enlarge-
ment, density reduction due to edema, and indistinct pancreatic margins owing to
inflammation and surrounding retroperitoneal fat stranding; complications include
pancreatic fluid collections and necrosis, pseudocyst, and vascular complications
[51] (Fig. 9.13).

9.6.5 Acute Mesenteric Ischemia

Postprandial pain, nausea, and vomiting can be symptoms of an acute mesenteric

ischemia, with a peak of incidence in the elderly. Etiology is mainly due to embolic
and thrombotic causes, other causes include nonocclusive mesenteric ischemia,
veno-occlusive mesenteric ischemia, and strangulating bowel obstruction [52].

9.6.5.1 Imaging Findings

Contrast-enhanced CT is the technique of choice for the diagnosis of acute mesen-
teric ischemia. Typical CT findings are related to bowel wall necrosis and perfora-
tion and include pneumatosis intestinalis (gas in intestinal wall), hepatic portal
venous gas, pneumoperitoneum, and variable amounts of free fluid. The intravenous
contrast medium administration is crucial to detect the vascular cause [53]
(Figs. 9.14 and 9.15).

a b

Fig. 9.13 Axial unenhanced CT (a, b) of a 71-year-old man with acute pancreatitis. Indistinct
pancreatic margins, surrounding retroperitoneal fat stranding (arrowhead), and diffuse pancreatic
calcifications (arrows) are showed
232 D. Caruso et al.

a b

Fig. 9.14 Axial portal venous phase CT images (a, b) of a 67-year-old woman with mesenteric
ischemia. Note the intramural bowel gas and adjacent fat stranding adjacent to bowel loops in left
hypochondrium (arrows)

a b

Fig. 9.15 Multiple axial arterial phase images (a) and coronal maximum intensity projection CT
images (b) of a 67-year-old woman with mesenteric ischemia, depicting obstructed superior mes-
enteric artery (arrows)
9 The Gastrointestinal System in Geriatric Patients 233

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The Male Urogenital System in Geriatric
Patients 10
Emilio Quaia and Filippo Crimí

Population aging is taking place throughout the world, and about 13% of the 76 mil-
lion persons in the USA were aged 65 years and older [1]. In Europe, there is the
oldest population in the world, with almost 25% of European projected to be aged
65 years or older by 2030. In particular, Italy and Germany are estimated to have the
oldest population in Europe. The progressive increase in the proportion of a popula-
tion that is elderly depends on changes in the survival of older persons and in the
birth rate [1]. The increasingly greater life expectancy of the population has been
mainly determined by reduced mortality at older ages. The five leading causes of
death, including heart disease, cancer, stroke, chronic lower respiratory tract dis-
ease, and Alzheimer’s disease, account for 69.5% of all death [1]. The renal causes
of death account only for 2% of all deaths and for 4% of chronic conditions in per-
sons aged >65 years, even though these represent an important cause of disability
and comorbidity in older patients.
Due to the progressive increase in the mean age of the population, it is very
important to know the morphologic changes of the kidney according to aging. As a
matter of fact, older individuals, often with a compromised renal reserve and sub-
stantial comorbidities, are the norm in the hospitalized population [2]. The func-
tional alterations of the aged kidney are characterized principally by a progressive
reduction of renal blood flow from about 600 to 300 mL/min/1.73 m2 and of glo-
merular filtration rate (GFR) from 130 to 60–80 mL/min. An accurate quantitation
of the GFR should always be performed in elderly patients before injection of iodin-
ated and gadolinium-based contrast agents. Moreover, when exposed to iodinated

E. Quaia (*)
Institute of Radiology, Padova University Hospital, Padova, Italy
Department of Medicine-DIMED, University of Padova, Padova, Italy
e-mail: [email protected]
F. Crimí
Institute of Radiology, Padova University Hospital, Padova, Italy
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 235
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_10
236 E. Quaia and F. Crimí

contrast agents, non-steroidal anti-inflammatory drugs, aminoglycosides, or hemo-

dynamic challenges (e.g., surgery and anesthesia, sepsis, volume depletion), this
at-risk patient population often develops an abrupt decline in GFR.
The kidneys undergo involutional changes with age. There is a gradual decline in
kidney weight starting after the age of 50 years, with the most marked decrease
occurring between the seventh and eighth decade. The progressive loss of kidney
mass appears to affect the renal cortex more than the renal medulla [3].
Microscopically, there is a reduction in the number of glomeruli and an increase in
glomerular sclerosis with increasing age [4]. The glomerular sclerosis in the elderly
is different from diabetic intercapillary diffuse sclerosis and focal glomerulosclero-
sis and corresponds to a progressive glomerular hyalinization, such that glomeruli
become shrunken, eosinophilic, and hypocellular masses.
The increase in the percentage of sclerotic glomeruli has been attributed to the
protein-rich diet characteristic of modern society which probably determines a state
of chronic glomerular hyperfiltration and hyperperfusion. A further cause would be
glomerular ischemia secondary to the changes in the renal blood flow occurring
with ages. The presence of atherosclerosis increases the incidence of glomerular
sclerosis, raising the possibility that glomerular sclerosis in the elderly is nothing
other than a reflection of vascular disease and thus should be considered a second-
ary phenomenon. On electron microscopic analysis, there is an increase in focal
thickening of both glomerular and tubular basement membranes, probably due to
the accumulation of type IV collagen [3]. The loss of glomerular mass is propor-
tional to the loss of tubular mass, so that the tubular balance is well preserved. The
outer cortical glomeruli are more extensively involved than the deeper glomeruli.
Moreover, in addition to glomerular sclerosis, there is a gradual increase in the
interstitial fibrosis.
Although most would agree that there is a decrease in the total number of glom-
eruli, there is a very wide scatter in the data, and many elderly people seem to retain
the same number of glomeruli as expected in younger persons [4]. The average
thickness of the glomerular basement membrane increases with age, but this does
not appear to be associated with any change in function. The volume of the mesan-
gium increases, but as this is accompanied by a decrease in glomerular volume, it is
difficult to draw any significant conclusion. The most significant changes appear in
the juxtamedullary glomeruli. Changes also take place in the tubules where there
may be irregular thickening of the basement membrane and, particularly in the dis-
tal tubule, the formation of diverticula. There is overall reduction in the tubular
volume, and this seems to parallel the reduction in glomerular volume. The intersti-
tium may contain areas of tubular atrophy and fibrosis. Renal arteries develop inti-
mal thickening and reduplication of the elastic lamina. Increasing tortuosity and
tapering of the interlobular arteries have been reported. Changes have been recog-
nized in the afferent arterioles, and there is evidence that there are differences
between those arterioles supplying the juxtaglomerular glomeruli and more cortical
glomeruli. It would appear that with increasing age, shunts develop between the
10 The Male Urogenital System in Geriatric Patients 237

afferent and efferent arterioles in the juxtamedullary glomeruli, whereas in the cor-
tical glomeruli the vessels become obliterated. The significance of these findings is
unclear, as it is difficult to separate out changes which may have been engendered
by hypertension and those due to aging alone [4].
BPH is an “age-dependent” disease with a reported prevalence in patients older
than 60 years of 50% that increases to 90% in patients older than 85 years. Half of
these patients show lower urinary tract symptoms and, therefore, should undergo
medical or surgical therapy. Imaging by US and MRI plays a fundamental role in
the detection of this condition and in the clinical decision-making for treatment.
Prostate cancer is the second most common cancer affecting men worldwide and the
risk of prostate cancer increases with age, it has been reported that the median age
of symptoms onset is 72 years. US was the most used technique to identify prostate
cancer but in the last years, thanks to the PI-RADS standardized reporting system,
MRI has progressively become the gold standard for the detection of prostate can-
cer. Prostatitis is also quite common in old men, especially chronic prostatitis, and
is pivotal to correctly identify this infection that in some cases can be misdiagnosed
as prostate cancer both at US and MRI.

10.1 Morphologic Alterations in the Kidney

of an Elderly Patient

Aging induces in the kidney a progressive, functional, and anatomic decay that does
not have a particular clinical impact. The fundamental alterations of renal morphol-
ogy in elderly patients include size reduction, parenchymal thickness reduction,
margin irregularities, and increased corticomedullary differentiation. In particular,
the most important morphologic alteration of the aged kidney is the volume reduc-
tion, approximately 20–30% in 80-year-old men, and a loss of weight that decreases
from 250–270 to 180–200 g after age 65 [5].
In elderly patients, the kidneys appear frequently reduced in their largest dimen-
sion (within the range of 9–9.5 cm) on grayscale US, with reduction in the renal
parenchymal thickness due to chronic reduction of the renal parenchymal perfusion
from nephroangiosclerosis. The renal capsule becomes thicker and there is an
increase of the renal sinus fatty tissue, in particular at the level of the renal hilum
(Fig. 10.1). Typically, there is evidence of irregular margins (Fig. 10.2a), frequently
with a pseudolobular appearance (Fig. 10.2b) and/or coexisting with renal paren-
chymal scars due to previous renal cortical infarctions (Fig. 10.2b). The corticome-
dullary differentiation appears usually increased due to the relative higher
echogenicity of the renal cortex compared to the medulla due to nephroangiosclero-
sis. Anyway, less frequently, the corticomedullary differentiation may also be
reduced. On color/power Doppler US, the renal peripheral vessels are usually not
visualized in the subcapsular renal parenchyma (Fig. 10.3).
238 E. Quaia and F. Crimí

Fig. 10.1 Kidney in an

80-year-old patient.
Contrast-enhanced CT,
transverse plane.
Reduction of renal cortical
thickness and increase of
the renal sinus fatty tissue
at the renal hilum

a b

Fig. 10.2 (a, b) Different grades of renal margin irregularities. Longitudinal grayscale US scan.
(a) Reduction of the renal parenchymal thickness with renal contour irregularities (arrows) and
increased corticomedullary differentiation. (b) Diffuse renal margin irregularities also with evi-
dence of renal parenchymal scars (arrows) due to previous regional infarctions. The interposed
renal parenchyma presents a pseudolobar appearance

On contrast-enhanced CT a typical diffuse irregularity of margins is identified,

often associated with a reduced cortical thickness or renal parenchymal scarring due
to previous renal infarcts (Fig. 10.4). Renal parenchymal retention cysts (Fig. 10.5a)
and renal sinus cysts (Fig. 10.5b) are frequently identified and probably develop
because of inflammatory reactions and infections that occur in the distal tract of the
tubuli [6]. On CT urography these fundamental morphologic changes are frequently
associated with calyceal alterations with narrowing of the first-order calyces and
multiple cysts of the renal sinus.
10 The Male Urogenital System in Geriatric Patients 239

a b

Fig. 10.3 (a, b) Fundamental morphologic alterations of the kidney in the elderly patient. (a)
Grayscale US. Increased echogenicity of the renal parenchyma with reduced corticomedullary
differentiation. (b) Power Doppler US. Reduced renal parenchymal vascularization at the level of
the subcapsular region (arrows)

a b

Fig. 10.4 (a, b) Fundamental morphologic alterations of the kidney in the elderly patient.
Contrast-enhanced CT, excretory phase. Coronal reformation. Diffuse reduction of the renal corti-
cal thickness with overt focal irregularities of renal margins (arrows)
240 E. Quaia and F. Crimí

a b

Fig. 10.5 (a, b) Contrast-enhanced CT showing a large renal parenchymal retention cysts (a) and
renal sinus cysts (b)

10.2 Nephrosclerosis

Nephrosclerosis is the term used for the renal pathology associated with sclerosis of
renal arterioles and small arteries due to medial and intimal thickening as a response
to hemodynamic changes, aging, genetic defects, or some combination of these and
to hyaline deposition in arterioles [7]. The resultant effect is focal ischemia of the
renal parenchyma supplied by vessels with thickened walls and consequent nar-
rowed lumen [7]. Some degree of nephrosclerosis is present at autopsy with increas-
ing age preceding or in the absence of hypertension. Hypertension and diabetes
mellitus increase the incidence and severity of the lesions. In nephrosclerosis, there
is a general hardening of the kidney due to overgrowth and contraction of interstitial
connective tissue. Nephrosclerosis may be compared to the arteriosclerosis of the
small renal arteries, and it is due to renovascular disease, mainly chronic hyperten-
sion. The renal vascular alterations of hypertension depend on the severity of the
blood pressure elevation and whether the process accelerates to malignant hyperten-
sion. Arteriolosclerosis of small cortical renal arteries, interlobar, arcuate, and inter-
lobular is a common feature of the kidney in patients with systemic arterial
hypertension and particularly in elderly patients [8].
In nephroangiosclerosis, both kidneys are usually symmetrically reduced in their
diameters with cortical scars. Cortical echogenicity is increased with increased or
reduced corticomedullary differentiation according to the grade of echogenicity of
the renal medulla. Color and power Doppler US reveal nonspecific reduction of
vascularization (Fig. 10.6). If compared to the younger population, renal RIs are
typically increased (>0.7 and frequently around 0.8) (Fig. 10.7). Renal perforating
arteries and veins [9] are much more visible in the kidneys of nephroangiosclerotic
patients in comparison with normal subjects since they enlarge in nephroangioscle-
rosis and present normally directed flows from the kidney toward the renal capsule.
10 The Male Urogenital System in Geriatric Patients 241

a b

c d

Fig. 10.6 (a–d) Fundamental morphologic alterations of the kidney in the elderly patient.
Reduction of the renal parenchymal thickness, margin irregularities, and increased corticomedul-
lary differentiation are evident on grayscale US (a). (b) Color Doppler US, longitudinal scan.
Reduction of renal cortical vascularization. (c, d) Doppler interrogation of the intrarenal segmental
arteries with increased arterial resistive indices

Fig. 10.7 Fundamental morphologic alterations of the kidney in the elderly patient. Color Doppler
US with Doppler interrogation of renal segmental artery. Increased arterial resistive index mea-
sured at the level of one renal segmental artery of the lower renal pole
242 E. Quaia and F. Crimí

10.3 Renovascular Disease

The geriatric population is affected by many vascular diseases since the incidence
of atherosclerosis increases with age. Generally, the imaging of vascular diseases
in the elderly is complicated by the presence of coexisting diseases, while the
image quality is degraded due to obesity and limited patient compliance.
Renovascular hypertension accounts for 0.5–5% of patients who have hyperten-
sion. The renovascular disease may manifest as asymptomatic renal artery steno-
sis, intractable or uncontrollable hypertension requiring multiple medications, or
ischemic nephropathy with progressive loss of renal function [10]. In young
patients, the most common cause of renovascular hypertension is fibromuscular
dysplasia, while in the elderly the most common cause is atherosclerosis mainly
localized in the ostial or proximal tract of the renal artery. Color Doppler US, heli-
cal computed tomographic (CT) angiography, angiotensin converting enzyme
(ACE) inhibitor scintigraphy with captopril, and magnetic resonance (MR) angiog-
raphy have been assessed in the diagnosis of renal artery stenosis. Digital subtrac-
tion angiography remains the gold standard for the diagnosis of renal artery
stenosis, and it is part of any endovascular intervention. Contrast-enhanced CT and
MR imaging angiographic techniques have improved in their detection of renal
artery stenosis, and MR angiography is generally considered more sensitive for
renal artery stenosis than US [11]. Anyway, kidney disease limits the use of con-
trast agents during CT and MR imaging examinations, and this is particularly true
in elderly patients. Moreover, coexistent cardiopulmonary diseases, such as con-
gestive heart failure, arrhythmias, and chronic obstructive lung diseases, limit the
ability of the elderly to hold breath during image acquisition [10]. Additionally,
cardiopulmonary diseases may preclude the use of some of the imaging modalities
because of the inherent contraindications, such as pacemakers in MR examina-
tions. Consequently, color Doppler US is the principal imaging technique employed
in the elderly for renovascular disease diagnosis.
The velocimetric analysis of Doppler trace derived from renal arteries is of pri-
mary importance to identify renal artery stenosis. Direct Doppler criteria have been
proposed for the detection of renal artery stenosis, including an increased peak sys-
tolic velocity (>150–180 cm/s) (Fig. 10.8) and end-diastolic velocity at the level of
the stenosis [12, 13], a poststenotic flow disturbance resulting in spectral broaden-
ing and reversed flow [12], an increased ratio (≥3.5) of peak systolic velocity in the
renal artery and aorta (renal-aortic ratio), and the presence of turbulence within the
renal artery [14, 15]. Although this technique is easy to perform, its accuracy is
questionable because the lack of an early systolic peak has a low sensitivity for
10 The Male Urogenital System in Geriatric Patients 243

a b c

d e f

Fig. 10.8 (a–f) Renal artery stenosis in a 75-year-old male patient. Worsening renal function was
precipitated by the treatment of hypertension with angiotensin converting enzyme (ACE) inhibi-
tors. (a) Doppler interrogation revealed aliasing at the level of the proximal tract of the right renal
artery with spectral broadening of the Doppler trace and increase of the peak systolic velocity. (b)
“tardus et parvus” profile of the waveform at intrarenal arteries. (c, d) CT angiography (CTA).
Severe stenosis of the right renal artery is confirmed (arrow) and a moderate stenosis of the left
renal artery (arrowhead). (e, f) angiography confirmed the stenosis that was treated with a stent

moderate stenoses, and the waveform is dependent on the maintenance of vessel

compliance, which limits its effectiveness in elderly patients and patients with ath-
erosclerosis [16, 17].
Downstream hemodynamic repercussions of renal artery stenosis in the distal
intrarenal arterial bed may be identified by Doppler US and may provide an indirect
diagnosis of renal artery stenosis. Numerous parameters are still debated [12],
except in cases of critical stenosis (>80%). In fact, even though intraparenchymal
arterial examination is technically easier than the evaluation of the main renal artery,
Doppler US findings in interlobar-arcuate renal cortical arteries are less reliable
than Doppler US findings on stenotic site since downstream repercussions are
absent in 20% of principal renal artery tight stenosis (>80%), for a well-developed
collateral blood supply. In the presence of a hemodynamically significant renal
artery stenosis, the Doppler trace reveals a “tardus et parvus” profile at poststenotic
or intrarenal tract of the renal artery [18, 16], consisting of an increased time to
reach the peak of the trace (acceleration time >70 ms) with loss of early systolic
peak and decreased acceleration index (<300 cm/s2). Poststenotic pulsus tardus is
caused by the compliance of the poststenotic vessel wall in conjunction with the
stenosis, which produces the tardus effect by damping the high-frequency
244 E. Quaia and F. Crimí

components of the arterial waveform. This information allows to identify those con-
ditions, which may produce false-positive or false-negative results when the tardus
phenomenon is used to predict hemodynamically significant upstream stenosis [16].
This is the case of the loss of vascular compliance in severe diffuse atherosclerosis
of elderly patients, which may prevent the tardus-parvus phenomenon decreasing
the sensitivity of color Doppler US [13]. Other findings that may be observed in the
intraparenchymal arteries in the presence of renal artery stenosis are decreased
resistive indices in interlobar-arcuate renal cortical arteries with increased side dif-
ference higher than 10% [12].
Contrast-enhanced CT angiography (CTA) and MR imaging angiography
(MRA) are also very sensitive and specific for the demonstration of renal artery
occlusion. Additional views provided by CTA allow for display of the renal arteries
in multiple planes and projections, often necessary for the depiction of stenosis
(Fig. 10.8). Calcified plaques limit the CT evaluation of luminal narrowing. In par-
ticular, in cases with extensive calcification, as is frequently observed in elderly
patients, renal artery stenosis can be obscured by MIP technique and requires care-
ful evaluation of the volume-rendered images. CTA can also depict secondary signs
of renal artery stenosis, including poststenotic dilatation and renal parenchymal
changes of atrophy and decreased cortical enhancement. CTA is also very helpful in
the post-treatment evaluation of renal stent grafts and can usually delineate between
the highly attenuating graft material and the intraluminal contrast material.
MRA is well suited for the evaluation of renal artery stenosis in the elderly.
Calcified atheromatous plaques do not hamper the assessment of the arterial lumen.
MR angiography provides information about the size of the kidney, collateral ves-
sels, and poststenotic dilatation. Contrast-enhanced axial MR imaging can directly
show the narrowing of the stenosis, and reformatted multiplanar imaging is often
used. Both MIP and volume rendering are useful and complimentary in the evalua-
tion of renal artery stenosis. Axial images alone are not sufficient for the evaluation
of renal artery stenosis because the renal arteries often have a tortuous course, espe-
cially in elderly patients. Multiplanar reformations are very useful, in particular to
show renal artery occlusion.

10.4 Renal Infarction

Nontraumatic acute renal infarction is quite common in elderly patients, and it may
present the same symptoms of stone colic or acute pyelonephritis. Renal infarction
may be caused by tight stenosis or occlusion of segmental or of the main renal artery
or by renal artery embolization due to renal angioplasty, atrial fibrillation, and car-
diac valvular defects. Other causes of renal infarction are vasculitis, systemic lupus
erythematosus, drug-induced vasculitis, paraneoplastic syndrome, hypercoagulable
state, or acute venous occlusion [19]. Both CT and angiography are reference imag-
ing techniques in renal infarct detection, whereas US presents a lower sensitivity.
Even though large renal infarcts may be hypoechoic in comparison with the viable
renal parenchyma, segmental renal infarcts are usually isoechoic or rarely hyper-
echoic if hemorrhagic component is present.
10 The Male Urogenital System in Geriatric Patients 245

Renal infarcts often reveal a wedge shape with capsular base. Even though base-
line color Doppler US and power Doppler US present overt limitations to detect
renal perfusion defects due to the low sensitivity to low-velocity and low-amplitude
flow states, they may increase diagnostic capabilities of US in detecting renal
infarcts, especially in elderly or obese patients and in patients with renal diseases.
In renal infarct, color Doppler US and power Doppler US reveal absolute absence
of renal cortical flows, even though it is very difficult to differentiate renal segmen-
tal infarct from areas which appear poorly perfused due to underlying parenchymal
disease, deep renal position, and artifacts. Moreover, color Doppler US presents a
low accuracy in the detection of small renal infarcts in the subcapsular region for
limited spatial resolution and in the superior renal pole for the high Doppler angle
and for the depth position [20].
Recent advances in microbubble-based contrast agents, and dedicated contrast-­
specific modes, have determined the achievement of increased image contrast in
tissues. By transmitting at the fundamental frequency and receiving selectively har-
monic frequencies, the background signal from stationary tissues is markedly sup-
pressed resulting in a greater signal-to-noise ratio and a better visibility of renal
infarcts. Blooming and flash artifacts are eliminated, shadowing artifacts are less-
ened, both spatial and temporal resolutions are improved, and the brightness of
grayscale pixel does not depend on angle-dependent frequency shift estimates.
Differently from iodinated contrast agent and gadolinium-based contrast agents,
microbubbles are pure intravascular agents which are not excreted in renal tubules
and may be safely employed in patients with advanced chronic renal failure, which
is frequently observed in the elderly. Microbubble-based contrast agents and
contrast-­specific imaging techniques improve significantly the diagnostic confi-
dence level in identifying nonperfused renal parenchymal zones and allow a reliable
depiction of renal perfusion defects (Fig. 10.9). Renal perfusion defects due to renal
parenchymal infarction appear as single or multiple focal wedge-shaped areas of
absent, diminished, or delayed contrast enhancement in comparison to the adjacent
renal parenchyma after microbubble injection [21].

a b

Fig. 10.9 (a) Contrast-enhanced US after sulfur hexafluoride-filled microbubble injection. (b)
Contrast-enhanced CTA, corticomedullary phase. The left kidney shows partial parenchymal
infarction (arrow) in a 72-year-old woman with atrial fibrillation
246 E. Quaia and F. Crimí

a b

Fig. 10.10 (a, b) Renal artery thrombosis in a 75-year-old male patient. (a) Contrast-enhanced
CTA. Coronal reformation. The left renal artery is occluded by a complex thrombus (arrow) with
relative avascularity of the left kidney. (b) Contrast-enhanced CT. Corticomedullary phase shows
a complete renal infarction

Fig. 10.11 Renal

shrinkage due to chronic
vascular hypoperfusion
due to the tight stenosis of
the left renal artery.
Contrast-enhanced
CT. Corticomedullary
phase. The left kidney
(arrow) appears small and
without any sign of
function (contrast
excretion)

Contrast-enhanced CT is the reference imaging technique in renal infarct detec-

tion. The parenchymal appearance of renal perfusion defects depends on the site of
arterial occlusion, if segmental (Fig. 10.9) or the main renal artery is involved
(Fig. 10.10), and on thrombus age [19]. Contrast material-enhanced CT shows the
absence of enhancement in the affected renal tissue. Acute renal infarctions typi-
cally appear as wedge-shaped areas of decreased attenuation, while after the acute
phase of renal infarction, atrophy begins and the infarcted tissue contracts, leaving
a cortical scar. Chronic renal artery stenosis with persistent renal parenchymal
hypoperfusion leads to progressive shrinkage of the parenchyma with absent resid-
ual function (Fig. 10.11).
10 The Male Urogenital System in Geriatric Patients 247

10.5 Atheroembolic Renal Disease

Atheroembolic renal disease (renal artery atheroembolization) is a complication

of severe ulcerative atheromatosis of the abdominal aorta [22] or may be due to
renal angioplasty, atrial fibrillation, and cardiac valvular defects. Atheroemboli
localizes in vessels smaller than the interlobular arteries, so that renal infarction
does not occur and clinical picture is frequently bland [22] even though acute
renal failure is the mode of presentation in most cases. Atheroembolic renal
disease with acute renal failure may develop during or immediately after intra-
vascular surgical intervention, intravascular interventional procedures (e.g.,
renal angioplasty), or anticoagulation due to atheroemboli detached from the
renal artery wall. The most common clinical manifestation is the sudden onset
of flank or back pain with or without hematuria, proteinuria, fever, and
leukocytosis.
Color and power Doppler US is a first-line imaging procedure to detect renal
perfusion defect but presents clear limitations due to the relative insensitivity to
low-velocity and low-amplitude flow states [23]. Coley et al. [24] found a global
accuracy of color Doppler US for the detection of partial renal infarction of 20%.
Contrast-enhanced color and power Doppler US are limited by blooming and
flash artifacts, which may be attenuated by reducing the instrument gain settings,
also diminishing the detection of focal abnormalities in renal blood flow [23].
Contrast-­enhanced CT (Fig. 10.12) is the reference imaging technique to identify
renal perfusion defects [19]. Contrast-enhanced US (Fig. 10.13) represents a
very sensitive and reliable imaging technique in revealing the renal parenchymal
perfusion defects due to renal artery embolization [21]. Renal perfusion defects
may appear as multiple focal wedge-shaped areas of absent, diminished, or
delayed contrast enhancement in comparison to the adjacent renal parenchyma
after microbubble injection [21].

a b

Fig. 10.12 (a, b) Contrast-enhanced CT. Multiple renal parenchymal perfusion defects (arrows)
due to diffuse septic embolization are evident on both kidneys of an 85-year-old patient
248 E. Quaia and F. Crimí

a b

c d

e f

Fig. 10.13 (a–h) Renal artery embolization in an 82-year-old male patient presenting at the emer-
gency unit with acute flank pain on the right side. (a–d) Contrast-enhanced US after sulfur
hexafluoride-­filled microbubble injection. (e–h) Contrast-enhanced CT, nephrographic phase.
Multiple bilateral renal parenchymal perfusion defects (arrows), involving mainly the right kidney,
due to embolization of an ulcerated plaque of the thoracic aorta
10 The Male Urogenital System in Geriatric Patients 249

g h

Fig. 10.13 (continued)

10.6 Renal Vein Thrombosis

Renal vein thrombosis in elderly patients, as in adults and differently from infants,
is typically of insidious onset and is almost always overimposed on an established
disease [22]. Causes of renal vein thrombosis in elderly patients include idiopathic
nephrotic syndrome, especially that due to membranous glomerulonephritis, vol-
ume loss due to dehydration (often aggravated by diuretic therapy) with altered
renal blood flow, hypercoagulable states (malignancy), renal cell carcinoma, or
extrinsic compression of the renal vein (retroperitoneal fibrosis, lymphoma, etc.).
The process may progress without any clinical sign. Mild abdominal or back pain
may be present, but severe pain is uncommon. Pulmonary emboli occur during the
course of approximately 50% of patients with chronic renal vein thrombosis and are
frequently the first manifestation of this condition [22].
Diagnosis of renal vein thrombosis relies on the visualization of an echogenic thrombus
within a dilated renal vein devoid of flow signals on CD corticomedullary differentiation
on grayscale US. Doppler spectral analysis of renal arteries may reveal slightly increased
RIs and normal parenchymal venous flows, since collateral venous supplies open after
renal vein thrombosis. Absent or reversed end-diastolic flow in renal interlobar–arcuate
arteries has been described in transplanted kidney which lacks collateral venous supply.
US contrast agents facilitate identification of renal vein patency and thrombosis in cases of
technical failure and enhance detection of collateral venous blood supply. A mass is evi-
dent in the renal vein with renal enlargement and delayed renal function.
CTA and MRA show complete occlusion of the renal vein [19] which appears
dilated and heterogeneous, while the infracted kidney appears enlarged and with a
diffuse alteration of the nephrographic phase (Fig. 10.14). Renal vein involvement
by tumor (Fig. 10.15) is frequently identified in elderly patients and it is crucial in
the determination of surgical options for removing a renal tumor. The renal veins
are well depicted on CT during the corticomedullary or nephrographic phase of
contrast enhancement.
250 E. Quaia and F. Crimí

Fig. 10.14 Thrombosis of

the right renal vein.
Contrast-enhanced
CT. Nephrographic phase.
The renal vein appears
dilated and heterogeneous,
while the right kidney
appears enlarged and with
diffuse alteration of the
nephrographic phase

a b

Fig. 10.15 (a, b) Thrombosis of the left renal vein due to infiltrating papillary renal cell carci-
noma. (a) Unenhanced CT. (b) Contrast-enhanced CT. Contrast-enhanced CT. Nephrographic
phase. The renal vein appears dilated and heterogeneous (small arrow), while the left kidney (large
arrow) appears enlarged and with diffuse alteration of the nephrographic phase. The inferior vena
cava (IVC) is also involved and appears occluded by a tumoral thrombus

10.7 Renal Failure

10.7.1 Acute Renal Failure

In the elderly, the kidneys are more vulnerable when other pathologies occur, in
particular, atherosclerosis, arterial hypertension, diabetes mellitus, bacterial infec-
tions, and malnutrition. Most cases of acute renal failure in elderly patients are
caused by drugs or are secondary to dehydration, especially in patients with hyper-
tensive intrarenal nephrosclerosis. In elderly patients, the differentiation between
renal and prerenal cause of acute renal failure may be difficult because the RIs are
usually elevated for the preexisting renal parenchymal disease. Moreover, an elderly
patient with severe and prolonged prerenal acute renal failure leading to acute tubu-
lar necrosis may present increased RIs.
10 The Male Urogenital System in Geriatric Patients 251

Acute renal failure is a common complication of hypertensive nephrosclerosis in

elderly patients with mild chronic renal failure [25]. Worsening renal function may
be precipitated by the treatment of hypertension, mainly with ACE inhibitors, or by
other causes such as nephrotoxic drug or dehydration. The evidence of acute renal
failure without an apparent cause following therapy with ACE inhibitors highly sug-
gests renal artery stenosis in well-hydrated elderly patients. Other possible causes
of acute renal failure in these patients are renal artery thrombosis and atheroembolic
renal disease. Doppler US examination is the first imaging modality to be employed
in these patients to rule out renal artery stenosis. Identification of the kidneys of two
different sizes is suggestive of ischemic disease.
The demonstration of increased flow velocity at the level of renal artery stenosis is
diagnostic. Anyway, the Doppler evaluation of intrarenal and renal perforating arteries
can be useful in these patients since the direct assessment of the main renal artery may
be difficult due to bowel gas interposition and incomplete patient compliance. The
intrarenal vessels may show an altered waveform with a pattern corresponding to
pulsus tardus and parvus. Perforating arteries are vessels connecting the capsular
plexus with the interlobar and interlobular arteries, which became hypertrophic in
those pathologic conditions that reduce the blood flow through the renal artery.
Perforating arteries with flow toward the kidney have been detected and interrogated
in about 60% of kidneys with renal artery stenosis of hypertensive elderly patients
with acute renal failure. Conversely, in the kidneys with no ischemic arterial lesions,
only perforating arteries with flow toward the renal capsule were identified [9].
Acute cortical necrosis is a rare cause of acute renal failure, usually occurring in
extremely ill individuals, often as a result of obstetric complications, hemorrhagic
shock, disseminated intravascular coagulation, severe trauma, sepsis, shock, or
burns. Contrast-enhanced US or CT (Fig. 10.16) has been shown to be diagnostic of
acute cortical necrosis showing necrosis of the renal cortex with sparing of the renal
medulla appearing as enhancing renal medulla, nonenhancing renal cortex and a
thin rim of subcapsular tissue, and absent renal excretion of iodinated contrast agent
[26]. Necrosis results from constriction of small intracortical blood vessels with
preferential flow of blood away from the renal cortex. The likelihood that normal
renal function will return is low. Usually, the involved kidney becomes shrunken
and scarred. Cortical nephrocalcinosis may then develop [27].
Cholesteric renal embolization represents an acute diffuse renal vessel emboliza-
tion, frequently manifesting with acute renal failure. Clinical diagnosis includes the
presence of livedo reticularis due to distal embolization in the lower extremities and
cholesterol crystals on the eye fundus examination. Color Doppler US examination
is not useful to diagnose this pathologic entity due to the small size of renal perfu-
sion defects. In cholesteric renal embolization, the identification of small renal per-
fusion defects in the renal subcapsular region is penalized by the limited spatial
resolution of US which cannot identify renal perfusion defects smaller than 5 mm
since in this clinical situation the renal perfusion defects are often very small to be
detected by contrast-enhanced US. Anyway, if larger or equal to 5 mm, renal perfu-
sions defects may be identified on contrast-enhanced US after microbubble injec-
tion (Fig. 10.17). Microbubble-based agents should be always employed to exclude
252 E. Quaia and F. Crimí

a b

Fig. 10.16 (a–c) Renal acute cortical necrosis. An 80-year-old patient with aortic endoprosthesis
was admitted to the emergency unit with acute renal failure. The absence of contrast enhancement
in the superficial cortex of the left kidney (arrow) is identified after microbubble injection (a). (b,
c) Contrast-enhanced CT confirmed the existence of diffuse renal cortical necrosis in the left kid-
ney (arrow)

a b

c d

Fig. 10.17 (a–d) Cholesteric renal embolization in a 70-year-old female patient presenting with
acute renal failure. Baseline color Doppler US (a, b) does not allow the identification of renal
perfusion defects. Contrast-enhanced US (c, d) allows a reliable depiction of renal perfusion
defect (arrow)
10 The Male Urogenital System in Geriatric Patients 253

renal infarcts in every old patient presenting with a renal colic-like pain in the
flank region.

10.7.2 Chronic Renal Failure

The proportion of elderly individuals is growing rapidly in all societies, and the
incidence of chronic kidney disease among elderly people increases constantly [28].
Therefore, the accurate monitoring of kidney function, that is GFR, in elderly peo-
ple is of considerable clinical interest in order to detect individuals who are at risk
for developing chronic kidney disease. The management of end-stage renal failure
in the elderly should not be significantly different from that in younger patients and
should be based on the capacity for rehabilitation.
Chronic kidney disease is an important problem in the elderly and is associated
with a high risk of kidney failure, cardiovascular disease, and death [29]. The disor-
der is indicated either by a GFR of less than 60 mL/min/1.73 m2 of body surface
area or by the presence of kidney damage, assessed most commonly by the finding
of albuminuria for 3 or more consecutive months [30–32]. In persons 70 years of
age or older, the percentage of people with a chronic kidney disease is around
30% [29].
Risk factors for chronic kidney disease include an age of more than 60 years,
hypertension, diabetes, cardiovascular disease, and a family history of the disease.
According to a recent series, diabetic nephropathy, obstructive uropathy, and hyper-
tensive nephrosclerosis were the major causes of chronic renal failure and accounted
for 80% of total chronic renal failure in the elderly [33].
Recommendations for evaluating people at increased risk are to measure urine
albumin to assess kidney damage and to estimate the GFR with an equation based
on the level of serum creatinine [32]. Older adults who suffer an acute injury to the
kidneys—from trauma, surgery, or illness—are at dramatically increased risk of
later end-stage renal disease.
Special care should be used in patients with chronic renal failure when the IV
injection of iodinated or gadolinium-based agents is planned. Iodinated contrast
agents should be employed in patients with chronic renal failure only before and
after proper hydration, while gadolinium-based contrast agents should not be
employed in patients with a GFR value below 30 mL/min. Differently from iodin-
ated contrast agent and gadolinium-based contrast agents, microbubbles may be
safely employed in patients with advanced chronic renal failure, especially in the
evaluation of renal masses and perfusion defects.
US reveals reduced renal length and cortical thickness and a hyperechoic renal
parenchyma with a poor visibility of renal pyramids and of renal sinus. Doppler US
reveals a reduced parenchymal perfusion and increased resistive index (RI) values.
In elderly patients with mild chronic renal failure, acute renal failure represents a
254 E. Quaia and F. Crimí

common complication of hypertensive nephrosclerosis [25]. Worsening renal func-

tion may be precipitated by the treatment of hypertension, mainly with ACE inhibi-
tors, or by other causes such as nephrotoxic drug or dehydration.
The evidence of acute renal failure without an apparent cause following therapy
with ACE inhibitors highly suggests renal artery stenosis in well-hydrated patients.
Doppler US examination is the first imaging modality to be employed in these
patients to rule out renal artery stenosis. Other possible causes of acute renal failure
in patients with mild chronic renal failure are renal artery thrombosis and atheroem-
bolic renal disease. Many urological interventions can precipitate or exacerbate
chronic kidney disease, most notably radical nephrectomy.

10.8 Obstructive Uropathy

In elderly patients, acute urinary tract obstruction can occur anywhere in the urinary
tract from the renal papilla to the urethral meatus and may be determined by a plenty
of causes. As in some patients, obstruction may be completely asymptomatic even
though, most frequently, it manifests with clear clinical symptoms.
Hydronephrosis may also be absent in the acute obstruction of the urinary tract
principally due to hypovolemia, dehydration, or nephrosclerosis. The most impor-
tant causes of urinary tract obstruction in elderly patients are urinary stones, tumors
of the urinary tract and ureter, and benign prostatic hyperplasia (Fig. 10.18).
The obstruction of the urinary tract, if not treated, usually determines a progres-
sive atrophy of the renal parenchyma which is frequently observed in elderly
patients.
Chronic obstructive uropathy (Fig. 10.19) may be determined by the tumoral
infiltration of the ureteral wall or by chronic incomplete obstruction of the ureter,
which may be suddenly complicated by an acute event such as infection.
10 The Male Urogenital System in Geriatric Patients 255

Fig. 10.18 Static-fluid

MR urography in an
85-year-old man patient
with benign prostatic
hyperplasia. Bilateral
fourth-grade
hydronephrosis

a b

Fig. 10.19 (a, b) Contrast-enhanced CT, excretory phase. Chronic urinary tract obstruction of the
right kidney (arrow) due to tissue scarring of the lower ureter. The kidney appears small and with-
out any sign of function (contrast excretion). Perirenal strands with dilatation and wall thickening
of the renal pelvis are also evident on the right kidney
256 E. Quaia and F. Crimí

10.9 Renal Infections

Acute pyelonephritis is an infectious disease involving both renal parenchyma and

renal pelvis mucosa which can be diffuse or focal. Diffuse pyelonephritis is an
infection involving the entire kidney, even though the severity of the process may
vary in extension (in one or both kidneys). Focal pyelonephritis is a localized infec-
tion of the kidney appearing as a wedge- or round-shaped parenchymal lesion,
which can regress if well treated or evolve to a collection extending toward the peri-
and pararenal spaces. Focal and diffuse pyelonephritis may resolve with the evi-
dence of normal renal parenchyma or scarring or may evolve with liquefaction and
formation of nephric or perinephric abscesses.
Pyelonephritis is the most common cause of gram-negative bacteremia in elderly
patients admitted to a community hospital. Acute pyelonephritis can be severe in the
elderly as in people who are diabetic or immunosuppressed with frequent evidence
of renal abscesses (Fig. 10.20). Appropriate antibiotic therapy and, of equal impor-
tance, a lack of serious associated medical illnesses contributed to the 97% survival.
An increased incidence of bacteremia and septic shock distinguishes acute, symp-
tomatic, and bacterial pyelonephritis in the elderly from that in young patients and
particularly in women [34].
Pyonephrosis is the most common complication of pyelonephritis in elderly
patient when ureteral obstruction is present. Urinary tract obstruction due to a uri-
nary stone is the most common cause of pyonephrosis (Fig. 10.21).

a b

Fig. 10.20 Pyelonephritis with diffuse abscessual evolution in a 70-year-old diabetic woman pre-
senting with septic shock (a) Grayscale US. Longitudinal scan. The left kidney appears increased
in dimension with multiple cystic lesions (arrows). (b) Contrast-enhanced CT during the nephro-
graphic phase after iodinated contrast injection. Both kidneys appear involved by multiple absces-
sual lesions (arrows). (c) Gross autopsy specimen confirming multiple renal abscesses (arrows)
10 The Male Urogenital System in Geriatric Patients 257

a b

c d

e f

Fig. 10.21 (a–f) Pyonephrosis in an 82-year-old woman presenting with acute right flank pain.
Grayscale US, longitudinal (a) and transverse scan (b). The right kidney presents dilatation of the
intrarenal urinary tract (white arrow) with diffuse corpuscular echogenic content and evidence of
renal stones (black arrow) lying in the renal pelvis with posterior acoustic shadowing. (c–f) Contrast-
enhanced CT, nephrographic phase. The right kidney (large arrow) presents increased dimensions,
multiple renal stones lying in the renal pelvis, and dilatation and diffuse thickening of the renal pel-
vis. Renal parenchyma presents also some abscesses (small arrows) due to infection diffusion
258 E. Quaia and F. Crimí

10.10 Neoplastic Pathologies

Frequently, urologists are confronted with an elderly patient (≥75 years of age) with
a renal mass seeking treatment. As the population ages, comorbidities become more
confounding in predicting patient outcome to therapy and may influence the appli-
cation of surgical therapy with curative intent to elderly patients [35]. Epidemiological
studies show an increasing incidence of renal cell carcinoma over the past two
decades, and interestingly, this increase has included a larger proportion of elderly
people. The presentation of renal cancer has evolved. There has been an increase in
the incidence of cases in the USA and several European countries and, at the same
time, a shift to incidentally diagnosed, smaller, localized tumors in a slightly older
population [36].
Generally, in elderly patients there is an increase in neoplastic disorders includ-
ing clear cell-type renal carcinoma and transitional cell carcinoma (TCC). The
median age of presentation of renal cell carcinoma is in the sixth decade of life.
Conversely, transitional cell carcinoma of the upper urinary tract is commonly seen
in older patients, usually between the sixth and eighth decade of life. This increased
incidence is mainly due to the more widespread use of imaging technology [37].
Most renal tumors are completely asymptomatic and are found incidentally in
elderly patients during imaging of the upper abdomen mainly by US (Fig. 10.22).
There is a great variance of growth rate with the majority of small renal tumors
(≤3 cm in diameter) in the elderly, with a prevalence of low growth rate (0.35 cm/
year with a median range of 0–10 cm), and a low incidence of distant metastases
[38]. Conversely, the majority of larger renal tumors usually present local invasive-
ness (Figs. 10.23 and 10.24) and distant metastases (Fig. 10.25). A “wait and see”
observational approach for renal masses 1.5 cm or smaller in the elderly can be
suggested [39].
TCCs are relatively rare tumors of the kidney, while they are commonly seen in
older patients usually between the sixth and eighth decade of life with a mean age

a b

Fig. 10.22 (a, b) Small renal tumor incidentally found in a 75-year-old male patient during US
examination of the abdomen. Unenhanced CT scan (a) showed a solid exophytic mass (arrow)
with enhancement after contrast injection in arterial phase (b). Clear cell-type renal cell carcinoma
is identified after partial nephrectomy
10 The Male Urogenital System in Geriatric Patients 259

a b

c d

Fig. 10.23 (a–d) Clear cell-type renal cell carcinoma in a 75-year-old man with hematuria. Local
tumoral invasiveness. (a) Grayscale US. A solid renal mass (arrow) is identified on the right kid-
ney. (b, c) Contrast-enhanced CT. Nephrographic phase shows a renal mass (arrow) on the right
kidney with invasion of the renal pelvis. (d) Photograph of gross specimen. Evidence of invasion
of the renal pelvis which justified the presenting symptom hematuria

of 65 years. TCCs of the renal pelvis or calices present an incidence of 5–15% of all
malignant tumors of the kidney [40, 41]. The incidence in men exceeds that in
women and the usual sex ratio is between 2:1 and 4:1 [41]. Over 85–90% of upper
urinary tract tumors are TCCs, with the renal pelvis (Fig. 10.26) being more com-
monly involved than the ureter [42]. Renal lymphoma occurs in all age groups, even
though the disease usually affects adults (average age, 60 years) and frequently
elderly patients. Renal involvement with lymphoma occurs much more commonly
with non-Hodgkin disease, the majority of patients having intermediate- or
260 E. Quaia and F. Crimí

a b

Fig. 10.24 (a, b) Clear cell-type renal cell carcinoma in an 82-year-old man. Local tumoral inva-
siveness. Contrast-enhanced CT. (a) Transverse plane. (b) Sagittal plane. Corticomedullary phase
shows a large solid renal mass of the right kidney invading the adjacent liver parenchyma (arrow)

high-­grade lymphomas including Burkitt and histiocytic types [43]. Lymphoma that
is isolated to the kidney as a primary site of involvement is quite rare, whereas addi-
tional sites of extranodal involvement are common and are seen in most patients at
the time of diagnosis. Lymphoma typically involves the kidney in one of the several
recognizable patterns including multiple renal masses, solitary masses, diffuse renal
infiltration, renal invasion from contiguous retroperitoneal disease (Fig. 10.27),
perirenal disease, or atypical patterns of renal involvement with invasion of the
renal pelvis.
10 The Male Urogenital System in Geriatric Patients 261

a b

c d

Fig. 10.25 (a–d) Clear cell-type renal cell carcinoma in a 77-year-old man. (a) Contrast-enhanced
CT. Nephrographic phase shows a heterogeneous large renal mass on the lower pole of the right
kidney. (a, b) Multiple enlarged lymph nodes (small white arrow) are identified in the retrocaval
nodal site. (c) Floating thrombus (large white arrow) in the inferior vena cava is also present. (d)
Distant bone metastasis is visualized on the right acetabulum (large arrow)
262 E. Quaia and F. Crimí

a b

Fig. 10.26 (a, b) Transitional renal cell carcinoma in a 70-year-old man with hematuria. (a)
Contrast-enhanced CT. Coronal (a) and sagittal reformations (b). A solid endoluminal tumor
(arrow) in the left kidney pelvis

a b

Fig. 10.27 (a, b) Renal lymphoma in a 67-year-old male patient with a known non-Hodgkin
disease retroperitoneal disease. (a) Contrast-enhanced CT, transverse plane. Direct and extensive
renal parenchymal invasion from contiguous retroperitoneal disease. (b) Photograph of gross spec-
imen from autopsy. Gross pathologic examination reveals yellow/gray tumor with extensive renal
parenchymal invasion
10 The Male Urogenital System in Geriatric Patients 263

10.11 Prostate

10.11.1 Benign Prostatic Hyperplasia (BPH)

In elderly patients it is common to find a condition of BPH, since it is an “age-­

dependent” disease with a reported prevalence in patients older than 60 years of
50% that increases to 90% in patients older than 85 years [44]. Up to 50% of these
patients show lower urinary tract symptoms that include obstructive symptoms,
such as incomplete emptying, intermittent voiding, weak stream, and straining, and
irritative urinary symptoms, such as frequent voiding, urgency, and nocturia [44–
46]. A clinical questionnaire, the International Prostate Symptom Score, divides the
patients in those with mild, moderate, or severe symptoms [47]. Men showing mod-
erate or severe symptoms are addressed to medical therapy, with α-blockers or
5α-reductase inhibitors, or minimally invasive surgical interventions to reduce pros-
tate volume and improve the symptoms [48]. Anatomically, the prostate is divided
into a stromal zone, named fibromuscular stroma, and four glandular zones that are,
respectively, periurethral, transition, central, and peripheral zone [44, 49]. Posteriorly
to the preprostatic urethra is located a zone of glandular tissue, named periurethral
glands [44, 49]. The first signs of BPH can be detected in the periurethral glands,
while later the glandular tissue of the transition zone is affected by the pathology,
producing consequently a hyperplasia of the surrounding fibromuscular stroma. The
progression of the hyperplastic glandular growth brings an increase in the gland
volume directed toward the bladder neck [44, 50]. Since hyperplasia affects both the
glandular and stromal tissue, there are two main mechanisms that produce the
symptoms and signs of urinary obstruction: the first is a compressive narrowing of
the urethra and bladder neck due to glandular hypertrophy and the second is an
increased tone of the muscles of the stroma around the urethra [44, 50]. Imaging is
indicated in case of hematuria, abnormal findings at digital rectal examination,
increased prostate-specific antigen (PSA), increased serum creatinine or urinary
retention [44]. Ultrasound (US) is the most common imaging technique used for
prostate examination. On US the BPH appears first ad spherical hypoechoic areas
antero-laterally and cranially to the verumontanum and, later, as multinodular
isoechoic nodules on a hypoechoic background in the transition zone [44, 51]. The
US examination can be transrectal, transabdominal, and transperineal and is crucial
to correctly evaluate the prostate volume and bladder voiding [52]. The total volume
can be calculated by measuring length, height, and width of the prostate, multiply-
ing the product by π/6 (Fig. 10.28); the dimensional cut-off that is generally used to
identify a BPH is 25 cm3 [44, 53]. In magnetic resonance imaging (MRI) examina-
tion the same formula can be used to calculate the prostate volume, allowing a better
definition of the intra-glandular anatomy and of the morphological changes caused
by BPH (Fig. 10.29) [48, 53].
264 E. Quaia and F. Crimí

a b

Fig. 10.28 (a, b) Benign prostatic hyperplasia (BPH) at ultrasound in sagittal (a) and transverse
plane (b). The calculated volume of the prostate is 65 cm3. Multiple isoechoic nodules on a
hypoechoic background are detected in the transition zone

a b

Fig. 10.29 (a, b) Benign prostatic hyperplasia (BPH) at MRI in transverse (a) and sagittal plane
(b). The calculated volume of the prostate is 52 cm3. Multiple typical encapsulated nodules of the
BPH can be appreciated in the transition zone
10 The Male Urogenital System in Geriatric Patients 265

10.11.2 Prostatic Cancer

Prostate cancer is the second most common cancer affecting men worldwide, with
an estimated number in 2020 of 1,400,000 new cases and 375,000 deaths [54]. The
vast majority of tumors arising from the prostate are carcinomas of epithelial origin
[55]. Prostate cancer originates mainly from the peripheral zone that is located pos-
teriorly and constitutes the main glandular component, nevertheless among one-­
fourth of the tumors originate from the transition zone that is located more anteriorly
[56]. The risk of prostate cancer increases with age: foci of prostate cancer have
been identified in 30–40% of men aged 60 years or older and the median age of
symptoms onset is 72 years [57, 58]. Hence, it is fundamental to have screening
procedures performed, especially in elderly patients. The screening tests are two:
the first is the physical examination with the digital rectal examination (DRE) and
the second one is the serum prostate-specific antigen (PSA) measurement that is
more reliable and widely used [59]. Anomalous findings in DRE or increased PSA
levels bring the suspect of prostate cancer and, therefore, imaging and eventually
biopsies are required to confirm the diagnosis. Since a few years ago, endorectal US
was the main imaging modality to verify the presence of prostate cancer [60]. At US
prostate cancer in around 60–70% of cases is detected as a hypoechoic nodule in the
gland, although the remaining 30–40% are iso or hyperechoic; anyway, the reported
accuracy of this technique is low, around 50–60% [60]. The accuracy of the tran-
srectal US has been reported to improve with the use of color/power Doppler tech-
niques, with the use of microbubble contrast agents and with elastography [60].
Nevertheless, in the last 10 years MRI has increasingly been used for the detection
of prostate cancer and its risk stratification. The first standardized system to report
MRI results was published in 2013, the Prostate Imaging Reporting and Data
System (PI-RADS), that was later updated in 2015 and now is currently used with
the 2.1 version published in 2019 [61–63]. The PI-RADS system assigns a score to
the lesions found by MRI in the prostate from PI-RADS 1 (very low risk of prostate
cancer) to PI-RADS 5 (very high risk of prostate cancer). The MRI characterization
of the lesion changes in the peripheral zone compared to the transition zone, in the
first one is mainly based on diffusion weighted imaging (DWI) signal of the nodule,
while in the second one on T2-weighed signal of the lesion [63]. For the peripheral
zone, the characteristics of the lesions are the following that are based mainly on
diffusion weighted imaging (DWI): PI-RADS 1 normal signal in DWI without
alteration at the apparent diffusion coefficient (ADC) map; PI-RADS 2 mild hypoin-
tensity in the ADC map but not focal hyperintensity in high b value DWI images;
PI-RADS 3 focal mild or moderate hypointensity in ADC map and mild hyperinten-
sity in high b value DWI images; PI-RADS 4 focal and marked hypointensity on the
ADC map with marked hyperintensity in high b value DWI images. <1.5 cm;
PI-RADS 5 same as 4 but ≥1.5 cm in greatest dimension or definite extraprostatic
extension/invasive behavior [63]. The contrast enhancement pattern plays a role in
this scale since PI-RADS 3 lesions with hypervascularization in arterial phase
should be classified as PI-RADS 4 [63] (Fig. 10.30).
266 E. Quaia and F. Crimí

a b

c d

Fig. 10.30 (a–d) Prostate MRI in a 72 years-old patient with PSA elevation. (a) T2-weighted
image showing a hypointense lesion (arrow) of the peripheral zone with a maximum diameter of
14 mm and without extracapsular extension; (b) focal and marked hypointensity of the lesion on
the ADC map (arrow); (c) marked hyperintensity of the lesion (arrow) in 1500 b value DWI
images; (d) contrast enhancement of the nodule after contrast injection (arrow). The lesion was
scored as a PI-RADS 4 nodule and targeted biopsies revealed a Gleason 7 prostate
adenocarcinoma

In the transition zone, the grading is based on the T2-wighted signal of the lesion:
PI-RADS 1 normal appearing transition zone (rare) or a round, completely encap-
sulated nodule; PI-RADS 2 a mostly encapsulated nodule or a homogeneous cir-
cumscribed nodule without encapsulation (“atypical nodule”), or a homogeneous
mildly hypointense area between nodules; PI-RADS 3 heterogeneous signal inten-
sity with obscured margins; includes others that do not qualify as PI-RADS 2, 4, or
5; PI-RADS 4 lenticular or non-circumscribed, homogeneous, moderately hypoin-
tense, and <1.5 cm in greatest dimension; PI-RADS 5 same as 4 but ≥1.5 cm in
greatest dimension or definite extraprostatic extension/invasive behavior [63]. If a
10 The Male Urogenital System in Geriatric Patients 267

PI-RADS 3 lesion ≥1.5 cm shows marked hypointensity on the ADC map and
marked hyperintensity in high b value DWI images, it should be classified as
PI-RADS 4 [63].
The PI-RADS system divides the prostate into 39 sectors/regions for three parts
of the prostate, the apex, the mid prostate, and the base of the prostate [63].
Multi-parametric MRI results allow to identify the suspicious lesions in the pros-
tate and to target the biopsies on them [64]. There are three techniques of MRI guid-
ance to perform a targeted prostate biopsy: the first is the cognitive fusion in which
the US operator performs the biopsy aiming in the prostate area where the MRI
results showed a lesion, the second is the direct MRI-guided biopsy that is a biopsy
performed directly in the MRI tube and guided by the images acquired during the
procedure and finally using device for images fusion where there is a co-registration
of stored MR images with real-time US scan [64].
MRI and contrast-enhanced CT can also identify loco-regional lymph node
metastases, at MRI or CT nodes with a short axis ≥1 cm, or ≥0.8 cm if round
shaped, are suspect for metastatic involvement [65]. A better accuracy for nodal
metastases detection has been reported for choline-PET/CT and prostate-specific
membrane antigen (PSMA)-PET/CT compared to CT and MRI [66].
For distant metastases contrast-enhanced CT is routinely used but MRI, choline-­
PET/CT, PSMA-PET, and NaF-PET/CT showed a better accuracy, especially in
detection of bone metastases [66].

10.11.3 Prostatitis

The bacterial prostatitis can be acute or chronic, with an estimated prevalence

around 10% [67]. Acute infections are most common in young men, while chronic
prostatitis often occurs in elderly patient with obstruction of the lower urinary tract,
even in absence of prior history of acute prostatitis [68]. The prostatitis can be focal
or diffuse, the peripheral zone is most frequently involved than the transition zone
and the most frequent cause is an ascending urethral infection from urine infected
by Escherichia Coli [68, 69]. During bacterial prostatitis, US shows a hypoechoic
rim around the gland with an increased flow at color Doppler, while MRI features
are low T2 signal intensity with increased contrast enhancement in arterial phase
and mild/moderate signal restriction in DWI sequences, due to infiltration of the
glandular tissue by inflammatory cells [68, 69]. Acute prostatitis could progress in
intraprostatic abscesses that at US and MRI examination appears as a fluid collec-
tion with thick irregular walls that present increased flow at color Doppler and con-
trast enhancement at MRI [68, 69]. In case of granulomatous prostatitis that can be
idiopathic, infective, iatrogenic, malacoplakia, or associated with systemic granulo-
matous disease, the US and MRI signal is very similar to prostate cancer., hence, it
is fundamental to collect a correct clinical history in order to avoid unnecessary
biopsies [68].
268 E. Quaia and F. Crimí

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The Female Urogenital System
in Geriatric Patients 11
Maria Assunta Cova, Lorella Bottaro, Cristina Marrocchio,
and Alessandro Marco Bozzato

11.1 Techniques of Imaging and Normal Anatomy

The female genital system includes the ovaries, fallopian tubes, uterus and cervix,
and vagina. The imaging appearance of the female genital system changes signifi-
cantly during a woman’s lifespan, reflecting the influence of hormones. After meno-
pause, hormonal levels diminish, leading to a progressive involution of the uterus,
cervix, ovaries, and vagina. The observed genital diseases also change in the elder-
lies, with increased incidence of neoplastic processes and of organ prolapse due to
laxity of the pelvic floor musculature and less frequent ovarian functional disor-
ders [1, 2].
Common indications for imaging the pelvis of a post-menopausal patient include
post-menopausal bleeding, pelvic pain or pressure, history of ovarian cysts, increas-
ing abdominal girth, or adnexal masses. Knowing the anatomy and normal imaging
appearance of the female pelvis in the post-menopausal woman is fundamental
since findings that can be normal in the reproductive years can be pathological when

M. A. Cova (*)
Department of Medicine, Surgery and Health Sciences, University of Trieste, Azienda
Sanitaria Universitaria Giuliano Isontina, Trieste, Italy
Department of Radiology, Azienda Sanitaria Universitaria Giuliano Isontina, Cattinara
Hospital, Trieste, Italy
e-mail: [email protected]
L. Bottaro
Department of Radiology, Azienda Sanitaria Universitaria Giuliano Isontina, Cattinara
Hospital, Trieste, Italy
e-mail: [email protected]
C. Marrocchio · A. M. Bozzato
Department of Medicine, Surgery and Health Sciences, University of Trieste, Azienda
Sanitaria Universitaria Giuliano Isontina, Trieste, Italy
e-mail: [email protected]; [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 271
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_11
272 M. A. Cova et al.

a b

c d

Fig. 11.1 Normal anatomy. (a) Normal US anatomy of the ovaries after menopause, appearing
small and homogeneously hypoechoic due to the lack of follicles (between calipers). (b) MR
appearance of the involuted ovaries, which have a decreased volume and a homogeneous interme-
diate signal intensity on T2-weighted images (arrows). (c) US appearance of the uterus after meno-
pause, decreased in size (between calipers). (d) Sagittal T2-weighted imaging showing an involuted
uterus, decreased in dimension and with less defined anatomical layers

observed in this age, and, conversely, physiological post-menopausal changes

should not be interpreted as pathological findings (Fig. 11.1).

11.1.1 Ultrasound

The first imaging modality is commonly a pelvic ultrasound since it is a widely

available, low-cost technique that does not use ionizing radiation. The transabdomi-
nal US allows the assessment of the uterus, the higher part of the cervical canal, and
the ovaries and should be performed with a full bladder. It provides a wider field of
view that can be useful to assess large pelvic masses, or in case the transvaginal
11 The Female Urogenital System in Geriatric Patients 273

approach does not allow an adequate assessment because of its smaller field of view,
e.g., in case of large uterine size or ovaries or other lesions located high in the pel-
vis. Transvaginal ultrasound (TVUS) is performed after bladder voiding and using
high-frequency probes. This approach has higher resolution in assessing the uterus,
the cervix, and the adnexa [3]. This is particularly true in older patients, in whom
decreased urinary bladder capacity, increased body habitus, and involution of the
organs to be studied may decrease the diagnostic accuracy of the transabdominal
approach [3].
The ovaries are generally identified by knowing their location with respect to the
uterus and recognizing the broad ligaments on whom posterior aspect they are
attached; however, they can be difficult to assess after menopause for their reduction
in volume and reduced number or absence of follicles [4]. The normal ovarian vol-
ume starts decreasing after 30 years, passing from 6.6 cm3 in women younger than
30 years to 2.6 cm3 in women 50–59 years old, and can continue decreasing during
menopause [5]. The mean post-menopausal volumes range from 1.2 to 5.8 cm3, and
a volume greater than 8 cm3 is always considered abnormal [3, 6, 7]. The post-­
menopausal ovaries appear more hypoechoic and homogeneous because of the
fewer or absent follicles. Small echogenic foci, 1–3 mm in size, with no associated
soft-tissue component, may be recognized, generally at the periphery. These may be
related to dystrophic calcifications in atretic follicles, epithelial inclusion cysts, or
millimetric cysts causing reverberation artifacts [3]. The fallopian tubes are not nor-
mally seen unless abnormal or surrounded by fluid. When recognized, the normal
tubes appear as elongated echogenic structures, directed posterolaterally from the
uterine horns, with echogenic fingerlike projections (fimbriae), and about 10–12 cm
in length and 1–4 mm in diameter [8]. The appearance and the size of the uterus
vary depending on the woman’s age [3, 9]. The uterine size in young women ranges
from 5 to 9 cm, while it decreases after menopause, varying from 3.5 to 7.5 cm in
length and from 1.2 to 3.3 cm in the anteroposterior diameter. On TVUS, a hyper-
echoic thin endometrium and a myometrium with coarse, speckled echotexture can
often be seen [3]. Free peritoneal fluid, when small and simple, can be normal in
early menopause, but in late menopause its presence is always abnormal and can be
related to gynecological and non-gynecological diseases [3].

11.1.2 Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a panoramic imaging modality with high con-
trast resolution. It provides an excellent assessment of the female pelvis as a second-
line imaging modality after US or as a primary imaging modality when US is not
feasible [3]. MRI can be performed on both 1.5 T and 3 T and pelvic phased array
coils are recommended at both 1.5 T and 3.0 T to increase signal-to-noise ratio (SNR),
with anterior and superior saturation bands. Antiperistaltic agents can be optionally
used to minimize artifact caused by bowel movement or contraction. The exam is usu-
ally performed with the patient in the supine position. The acquisition protocol will
depend on the specific pathology and organ to study; the standard protocol should
274 M. A. Cova et al.

include: T2-weighted images, which provide the most information, fat-saturated

T1-weighted sequences, useful to differentiate fat from hemorrhage in lesions with
high T1 signal intensity, diffusion-weighted images, and fat-saturated sequences after
the intravenous administration of gadolinium-based contrast medium [10].
The normal ovaries in the elderly patient can be difficult to recognize on
MRI. After menopause, the relative increase of stromal cells and reduction of follicu-
lar cells within the cortex results in a decreased T2-signal intensity and a homoge-
neous intermediate to low T1-signal intensity. Moreover ovaries show an enhancement
less or equal than the uterine myometrium, after contrast administration [3, 11].
Usually, the normal fallopian tubes are not visible on cross-sectional imaging. If
ascites are present, they may be outlined as serpiginous structures near the uterus,
and their course within the pelvis helps to differentiate them from the broad ligament.
The uterus usually has intermediate or low signal intensity on T1-weighted
sequences [12, 13], while, on T2-weighted images, it has three layers with different
signal intensities: the inner one, corresponding to the endometrium, is hyperintense,
the intermediate one, the junctional zone, is hypointense, whereas the outer one, i.e.,
the myometrium, has intermediate signal intensity [3, 14]. This uterine zonal anat-
omy may not be present in older women [3]. The endometrium is characterized by
the presence of glands, and its thickness usually ranges from 1 to 2 mm in old
patients [3]. The junctional zone can be hardly recognizable after menopause, and
its thickness must not be greater than 12 mm [3, 15, 16]. On post-contrast
T1-weighted sequences, the endometrium presents later and lower enhancement
than myometrium, which is characterized by high signal intensity in the early phases
[9]. A study with a small sample size has also reported that zonal fractional anisot-
ropy and ADC values of endometrium and myometrium in women after menopause
are lower compared to those in women before menopause [17].
On T2-weighted sequences, the cervix has three layers with different signal
intensities: the hyperintense innermost one, the so-called central zone, consists of
mucus and palmate folds; the hypointense middle one is the innermost part of the
fibromuscular stroma and is in continuity with the uterine junctional zone; the outer
one, i.e., the outermost part of the fibromuscular stroma, has intermediate signal
intensity [3, 9, 18, 19]. On post-contrast T1-weighted sequences, the middle zone
presents earlier enhancement than the other ones [9].
The vagina is a fibromuscular structure about 7 cm to 9 cm long, located poste-
riorly to the urethra and vesical trigone and anteriorly to the rectum [20]. It can be
divided anatomically into a lower third, below the level of the bladder base, a mid-
dle third, at the level of the bladder base, and an upper third, at the level of the vagi-
nal fornices [20]. The division is important for tumor staging and because of the
different lymphatic drainage, which is into the internal and external iliac lymph
nodes for the upper two-thirds, and the superficial inguinal nodes for the lower third
[20]. The vaginal mucosa appears as a T1-hypointense and T2-hyperintense thin
layer with enhancement after contrast administration. The mucosal layer appears to
be thinner in menopausal patients unless they are on hormonal replacement therapy
[20–22]. External to the mucosa, the vaginal wall appears hypointense on both T1-
and T2-weighted images, corresponding to the submucosal layer, consisting of
11 The Female Urogenital System in Geriatric Patients 275

collagen and elastic fibers, and the muscular layer, composed of smooth muscle
cells organized in an inner circular and outer longitudinal layer. Most externally,
there is the adventitia layer, in which a serpiginous T2-high-signal intensity can be
recognized, corresponding to the vaginal venous plexus [20, 21].
The vulva includes the mons pubis, labia majora and labia minora, clitoris, and
vestibule. It has low-to-intermediate signal intensity on T1-weighted images and
slightly high signal intensity on T2-weighted images [20].

11.1.3 Computed Tomography

The role of computed tomography (CT) in studying the female pelvis is limited and
is generally reserved to acute settings or for pelvic malignancies systemic staging.
When recognizable, the ovaries appear as small, roughly triangular structures of
soft-tissue density, often near the iliac vessels or uterus [3]. The gonadal vessels
may be an important anatomical landmark for their identification. On non-contrast
CT, the uterus appears as a uniform hypoattenuating formation, with a central zone
of lower attenuation representing the endometrial canal [9]. The vaginal mucosa,
which in fertile women is hyper-enhancing, becomes of similar density to that of the
vaginal wall in the post-menopausal age. The vaginal wall shows poor enhancement
after contrast administration [20]. Vaginal pathologies may be difficult to assess at
CT because of the similar density with the adjacent soft-tissue structures. The vulva
is identified as a triangular soft-tissue density structure within the perineum, poste-
rior to the symphysis pubis and anterior to the anal sphincter [23].

11.2 Ovaries

11.2.1 Endometriosis

Endometriosis results from the presence of aberrant endometrial tissue outside the
uterine cavity [24]. It is a common occurrence in the female population, with an
estimated 5 to 10% of women in the reproductive age being affected [25].
The pathogenesis of endometriosis is complex, particularly after menopause,
when it is unclear if it is a continuation or a reactivation of a previously existing
disease or a de novo condition. Estrogen exposure appears to have a key role;
indeed, due to the decreased estrogen levels after menopause, endometriotic lesions
in most cases regress in this age group [26] (Fig. 11.2).
Although endometriosis in post-menopausal patients is relatively uncommon, it
is estimated that about 2 to 5% of post-menopausal women are affected [27], and it
should be considered as a possible diagnosis. Hormone replacement therapy, espe-
cially estrogen-only treatments without progestin, and Tamoxifen use have been
associated with post-menopausal endometriosis [28–30]. Other risk factors include
a history of symptoms before menopause suggestive of endometriosis and condi-
tions that may raise the level of serum estrogens, such as obesity [28].
276 M. A. Cova et al.

a b

e f

Fig. 11.2 Endometriosis. (a) TVUS showing a unilocular lesion in the right ovary, with a homo-
geneous hypoechoic content and diffuse low-level internal echoes, the so-called ground glass
appearance (between calipers). (b–f) MRI of a different patient showing an endometrioid cyst in
the left ovary. Axial T2-weighted image (b) showing an ovoid mass with regular margins (white
arrow). The mass is characterized by a mostly cystic T2-hyperintense (b) and T1-hypointense (c)
content, and a hematic component in the dependent regions, separated by a fluid-fluid level. The
hematic component is in the subacute phase, showing T1-hyperintensity and T2-hypointensity
(black arrows), with restricted diffusion on DWI (d), as confirmed on the ADC map (e). In the
presence of a T1-hyperintense cystic content, it is always important to obtain fat-suppressed
T1-weighted images (f) to exclude the presence of fat. Note the large simple cystic mass in the
right ovary (asterisk, b)
11 The Female Urogenital System in Geriatric Patients 277

The identification of endometriosis in older patients may be an incidental finding

during imaging or surgery performed for other reasons. If symptoms occur, they are
non-specific and include pelvic pain, dyspareunia, dyschezia, and abnormal vaginal
bleeding. Symptoms can also be related to the specific organ involved, which may
be outside the pelvis [30].
Endometriosis is associated with an increased risk of ovarian cancer, particularly
the clear cell, endometrioid, and low-grade serous types [31–33]. The risk of malig-
nant degeneration of an endometrioma is estimated to be about 1% [34, 35]. In the
post-menopausal patient, the risk of malignancy is further increased because of the
older age and the long-standing history of ovarian endometriosis [35]. Therefore, it
is important to identify endometriosis in post-menopausal patients and carefully
assess the lesions to identify any suspicious features.

11.2.1.1 Imaging Findings

Endometriosis is characterized by endometrial implants, endometrial cysts, called
endometriomas, and adhesions [36]. The endometrial implants can be superficial
peritoneal deposits or deep infiltrating implants or nodules at least 5 mm in depth
[37]; extra-pelvic implants can also occur. Endometriomas, also called “chocolate
cysts” for their appearance, result from repeated cyclic hemorrhages within a deep
implant. The small endometrial implants, when active, may cause an inflammatory
response that ultimately leads to fibrosis and adhesions.
The most common localization of the endometrial foci are the ovaries, followed
by the uterine ligaments, posterior cul-de-sac, pelvic peritoneum, fallopian tubes,
sigmoid and rectal serosa, anterior cul-de-sac, and bladder [10]. In general, endo-
metriotic lesions after menopause seem to be less active and less extensive than in
pre-menopausal women [38].
Laparoscopy is the gold standard for the diagnosis of endometriosis [39].
Imaging is indicated when there is a clinical suspicion of endometriosis but equivo-
cal clinical history and examination. MRI is indicated as a second-line imaging
modality after US, if the lesions remain undetermined at US, before surgery for
optimal preoperative staging, or if there is a clinical suspicion of malignant degen-
eration [10, 40, 41].

US Findings
US is the most common modality used in the suspect of endometriosis. Particular
attention should be paid to the evaluation of the ovaries and the cul-de-sac, common
sites involved [39].
The US appearance of endometrial cysts is highly variable. The most common
one is a unilocular cystic lesion with a homogeneous hypoechoic content, with dif-
fuse low-level internal echoes, sometimes referred to as “ground glass” [39, 42].
Rarely, they may be completely anechoic, similar to a functional cyst [39].
Endometriomas may also appear as multilocular complex lesions, with thick
walls and septa, wall nodularity, and echogenic foci within the cyst wall [43, 44].
These echogenic foci are thought to be related to cholesterol deposits in the endo-
metrial wall and should be differentiated from wall nodules, which usually appear
278 M. A. Cova et al.

larger and less echogenic [39]. Also, the multilocularity may in some cases be due
to multiple adjacent separate cysts [39]. Malignancy should always be suspected in
the presence of a solid mural nodule; an increasing size of the cyst is another less
reliable signs of degeneration [45].
The heterogeneous appearance of the endometrioid cysts results in a broad range
of differential diagnoses, including functional cysts, tubo-ovarian abscesses, der-
moid cysts, and benign or malignant lesions [41]. The stability or minimal growth
at follow-up represents an important distinguishing feature from functional cysts, in
particular hemorrhagic ones, which may be very similar in appearance but generally
have a more acute onset and resolve in 4–6 weeks [39].

MRI Findings
Endometrial cysts have two typical patterns of presentation. In the early subacute
bleeding phase, they will be T1-hyperintense and T2-hypointense. In the later sub-
acute phase, they will be hyperintense on both T1 and T2 weighted images [39, 46,
47]. The shading sign, i.e., loss of signal within the lesion that can be seen on
T2-weighted images, is an important sign of endometriomas. This is due to the pres-
ence of hematic products in different stages of degeneration because of repeated
bleedings [39]. After contrast administration, subtraction images help detect any
enhancing tissue if there is a concern of malignant degeneration [37]. The differen-
tial diagnosis of endometriomas includes dermoid cysts, hemorrhagic cysts, muci-
nous cystic neoplasms, and an ovarian carcinoma with internal hemorrhage. The
absence of signal loss on fat-suppressed T1-weighted images confirms the hematic
content and rules out fat-containing lesions such as dermoid cysts [39, 48].
T1-weighted images help in the differential with mucinous cystic neoplasms, which
will show a high signal intensity but less than fat or blood. Differentiating an endo-
metrioma from a hemorrhagic corpus luteum can be more difficult; hemorrhagic
cysts are usually unilocular (while endometriomas are often multilocular and bilat-
eral), do not show the T2-shading sign, and mostly disappear at follow-up. An ovar-
ian carcinoma with internal hemorrhage will have features suggestive of malignancies
such as solid components, larger dimensions, and septations [39].
Endometrial implants will have variable signal intensities. They may have low
T1 signal intensity and high T2 signal intensity, similar to the normal endometrium,
or they can be hyperintense or hypointense on both T1- and T2-weighted images [39].
Adherences will appear as spiculated hypointense bands between organs, with or
without anatomical distortion, that in advanced disease may result in the so-called
kissing ovaries configuration, i.e., the ovaries displaced posteriorly and medially
toward one another [49].
Imaging features of endometriosis-associated malignancy are similar to the other
malignancies not related to endometriosis. On MRI, it will often have an intermedi-
ate T2 signal intensity, with avid enhancement and restricted diffusion. Enhancing
mural nodules and septations will be best appreciated on post-contrast T1-weighted
images with fat suppression and subtraction [30]. Restricted diffusion may also
occur in benign endometriomas due to the presence of blood products [50]. Another
non-specific sign is the loss of T2 shading [51]. Extra-ovarian malignancy
11 The Female Urogenital System in Geriatric Patients 279

associated with endometriosis may have an infiltrative appearance, and benign vari-
ants, e.g., polypoid endometriosis, may mimic features of malignancy [30].

11.2.2 Ovarian Masses

11.2.2.1 Imaging Approach to Adnexal Masses

The first imaging modality in women with a suspected ovarian mass is usually
TVUS [52]. US can provide important information on adnexal masses, including
their dimension, walls, margins, content (liquid or solid), presence of any septation,
and any associated finding such as the presence of free fluid in the pelvis. The color
Doppler can also provide important information on their vascularization.
Numerous scoring systems and algorithms have been proposed to develop more
objective US-based approaches to differentiate benign from malignant adnexal
lesions, among them, more recently, an Ovarian-Adnexal Reporting and Data
System for Ultrasound (O-RADS US) and for MRI (O-RADS MRI) [53–60].
The International Ovarian Tumor Analysis (IOTA) group published a consensus
paper to standardize the terms and definitions used when reporting an ovarian mass
at US [58]. According to their paper, when approaching an ovarian mass, its dimen-
sion, its morphologic features (presence of septa, solid components, solid papillary
projections, a regular or irregular internal wall), and its content (anechoic, low-level
echogenic, ground glass, hemorrhagic, or mixed echogenic) should be noted. Based
on these features, adnexal lesions can be classified qualitatively into one of the six
categories: unilocular cyst (unilocular cyst without septa and without solid parts or
papillary structures), multilocular cyst (at least one septum but no measurable solid
components or papillary structures), unilocular-solid cyst or multilocular-solid cyst
(unilocular or multilocular cyst with measurable solid component or at least one
papillary structure, respectively), solid tumor (solid component constituting 80% or
more of the tumor when assessed on two-dimensional section), or not classifiable
because of poor visualization. They also described the scoring for a subjective semi-
quantitative assessment of flow on color Doppler imaging, ranging from a score of
1, in which the lesion has no blood flow, to a score of 4, in which the lesion is highly
vascular with marked blood flow. The IOTA “Simple Rules” can be used to classify
an adnexal mass as benign, malignant, or indeterminate and are applicable to about
80% of ovarian masses [52, 61]. The IOTA “Easy Descriptors,” four for features
typical of common benign lesions and two suggestive of malignancy, can also help
recognize those lesions with typical characteristics of benignity or malignancy;
these descriptors are applicable to about 43% of adnexal masses [57].
Even using the IOTA Simple Rules, 22% of lesions remain indeterminate on US
[62]. As most of these turn out to be benign lesions, such as fibromas, MRI is indi-
cated in sonographically indeterminate masses, as their characterization has an
important impact on the therapeutic management of the patient [63]. In particular,
MRI is useful to further characterize a solid adnexal mass, or a complex adnexal
mass with equivocal features of malignancy, or to determine the organ of origin in
case of large pelvic masses or a mass adjacent to the uterus but whose origin cannot
280 M. A. Cova et al.

be clearly assessed [63]. Features that indicate a uterine origin are the presence of a
pedicle between the lesion and the uterus; the “bridging vessel sign” on contrast-­
enhanced T1-weighted images (i.e., the presence of vascular structures going from
the uterus to the lesion as it receives its blood supply from uterine vessels); and, in
case of uterine leiomyomas, the normal uterine tissue may be draped around the
lesion like a “claw” [46, 63]. Suggestive of an ovarian origin is the “ovarian beak
sign,” i.e., the presence of sharp angles between the lesion and the ovary [64]; also,
an ovarian fibroma will be separate from the uterus [63]. According to current
guidelines, the MRI protocol should include a sagittal T2-weighted sequence of the
pelvis, a T1- and T2-weighted sequences in the same orthogonal plane (axial or
coronal) and with the same slice thickness covering the mass, a DWI sequence, and
dynamic contrast-enhanced T1-weighted sequences [63]. If the lesion shows high
signal intensity on T1-weighted images, an axial fast spin-echo (FSE) T1-weighted
sequence with fat suppression needs to be acquired. If doubt exists on whether the
lesion belongs to the uterus or the ovary, 3D T1-weighted or FSE T1-weighted
sequences with fat suppression or FSE T2-weighted sequences may be acquired on
the axial plane of the ovary, which corresponds to the parallel plane of the endome-
trial cavity [10].

11.2.2.2 Ovarian Tumors

Ovarian cancer accounts for only 3% of female cancer, but it is the fifth most com-
mon cause of cancer-related mortality in women. The vast majority of ovarian can-
cers are detected at an advanced stage, with a poor prognosis. The strongest risk
factors for ovarian cancer are a familiar history of ovarian cancer and increasing
age, with an incidence steeply increasing after menopause [65]. In the early stages,
the tumor is often asymptomatic, while symptoms, such as bloating, pelvic or
abdominal pain, urinary symptoms, and palpation of an adnexal mass at physical
examination, are most frequent in an advanced disease [66]. US and MRI are used
to identify and further characterize adnexal masses, while contrast-enhanced CT,
MRI, and PET/CT are used for staging and follow-up [10]. MRI, in particular when
using DWI sequences, has a higher per-lesion sensitivity, especially for implants
smaller than 1 cm, smaller peritoneal implants, and involvement of adjacent
organs [10].

Epithelial Tumors
Epithelial tumors constitute 60% of all ovarian tumors and 85% of malignant ones
[67]. Their incidence increases with age, peaking in the sixth to seventh decade
[68]. They include serous, mucinous, seromucinous, endometrioid, clear cell,
Brenner tumors, and undifferentiated carcinoma [69].

Serous and Mucinous Tumors

Serous and mucinous tumors may be benign or malignant. Features suspicious for
malignancy include presence of solid tissue and papillary vegetations within mostly
multilocular cystic lesions, dimensions superior to 4 cm, thick (>3 mm) and irregu-
lar walls and thick septa, and large soft-tissue parts with necrotic foci [67, 70]
11 The Female Urogenital System in Geriatric Patients 281

a b

Fig. 11.3 Ovarian cystadenoma with features of malignancy. Coronal (a) and sagittal (b) CT scan
reconstructions showing a large abdominal multilocular cystic lesion (*) with the presence of
thick, irregular walls and septa, papillary projections within the lumen (arrow) and enhancing soft-­
tissue components with necrotic foci

(Fig. 11.3). The solid tissue will have intermediate signal intensity on T1- and inter-
mediate on T2-weighted images [70, 71]. The signal intensity of the papillary veg-
etations reflects their tissue architecture, composed of a stromal core lined by
neoplastic cells. They will appear as structures of intermediate signal intensity on
T1-weighted images and with a hypointense core lined by a hyperintense neoplastic
epithelium on T2-weighted images [67, 72]. Malignant lesions tend to have a faster
and more intense enhancement than benign lesions after contrast administration
[73]. Malignancy is also associated with ascites, lymphadenopathies, invasion of
pelvic organs, and peritoneal and omental implants, whose identification can be
helped by the DWI sequence, especially if small in dimensions [70, 71].
Serous cystadenomas appear as mostly unilocular cystic mass, with a thin wall or
septum and no vegetations. They have a homogeneous low signal intensity on
T1-weighted images and high signal intensity on T2-weighted images, with no
enhancement or enhancement of the thin walls alone after contrast administration
[67, 74, 75]. Serous cystadenocarcinoma can have discrete dimensions, are bilateral
in two-thirds of cases, and have malignant features at imaging [68].
Mucinous cystadenomas are multilocular cystic masses with thin walls or septa
and no vegetations, usually larger than serous cystadenomas [67, 71]. The signal
intensity will depend on mucin concentration, with T1 hypointensity and T2 hyperin-
tensity with higher water content, and T1 hyperintensity and T2 hypointensity with
thicker mucin [70]. Sometimes, multiple locules with variable signal intensities can be
observed, in an appearance referred to as “stained-glass” [76] (Figs. 11.4 and 11.5).
282 M. A. Cova et al.

a b

c d

e f

Fig. 11.4 Ovarian cystadenoma. (a, b) TVUS showing an ovoid mass with regular margins and
minimally thickened wall (3 mm) (between calipers, a), with a finely corpuscular content. At the
color Doppler analysis, neither the mass nor its thickened wall exhibit any significant vasculariza-
tion (b). (c–f) MRI exam of the same patient showing a mass in the left ovary with minimally
thickened wall, well appreciated on the coronal T2-weighted sequence (arrow, c), and a content
with high signal intensity on T2-weighted images and slightly low signal intensity on T1-weighted
images (arrow, d). There is no restricted diffusion (e) and only the wall shows enhancement (f).
The mass has no aggressive features
11 The Female Urogenital System in Geriatric Patients 283

a b

Fig. 11.5 Mucinous cystadenoma. Axial contrast-enhanced CT scan (a, b) and sagittal recon-
structions (c) showing a cystic mass of significant dimensions within the abdomen, with thin, mini-
mally enhancing wall and septa (arrows), and no vegetations. The mass dislocates the abdominal
organs posteriorly

Mucinous cystadenocarcinoma is a large multilocular cystic mass and can be associ-

ated with pseudomyxoma peritonei, due to rupture of the cyst or peritoneal metaplasia
[68, 74, 77].
Cystadenofibromas are uncommon epithelial neoplasms that are partly fibrotic.
The fibrotic component will have a low signal intensity on T2-weighted images and
the differential diagnosis with malignant solid neoplasms may be difficult [68, 78].

Non-Serous Non-Mucinous Epithelial Ovarian Tumors

Endometrioid carcinoma (Fig. 11.6) accounts for 10–15% of ovarian tumors. It may
occur in the setting of endometriosis, and in up to 33% of cases endometrial
284 M. A. Cova et al.

a b

Fig. 11.6 Endometrioid carcinoma. (a, b) Axial contrast-enhanced CT scan at different levels of
a patient admitted to the emergency room for left flank pain. In the abdomen, there is a hypodense
voluminous solid mass (white asterisks, a, b), slightly heterogeneous in density and with no
enhancement after contrast administration (unenhanced CT not shown). A small amount of fluid in
its most caudal region is also present (black asterisk, b). The patient underwent surgery, and this
was confirmed to be an endometrioid carcinoma

hyperplasia or synchronous endometrial carcinoma are also present [24, 63, 79].
The tumor appears as a complex cyst with solid components, with the solid compo-
nent having an intermediate or heterogeneous signal intensity and enhancement
after contrast administration [67, 80]. The involvement is bilateral in about 40% of
cases, and this frequently indicates the spread of the disease beyond the genital
tract [24].
Clear cell carcinomas (Fig. 11.7) represent about 5% of ovarian tumors and may
be solid or cystic [67, 68]. The usual MR appearance is a unilocular cyst with solid
protrusions into the lumen, with very variable T1 signal intensity [67].
Brenner tumors are rarely malignant and constitute 2–3% of ovarian tumors.
They are associated with other ovarian tumors in 30% of cases, and the large major-
ity are unilateral [67]. There is a cystic and a solid variant [24]. They appear as
multilocular cystic masses with a solid component that is T2-hypointense and has at
least a moderate enhancement after contrast administration. Amorphous calcifica-
tions may be present [46, 67].

Germ Cell Tumors

Germ cell tumors comprise about 20% of ovarian tumors and 2–5% of all ovarian
malignancies [81, 82]. They include mature teratomas (also called dermoid cyst),
immature teratomas, dysgerminomas, endodermal sinus (yolk sac) tumors, embryo-
nal carcinoma, choriocarcinoma, and mixed germ cell tumors [69]. Ovarian germ
cell tumors arise primarily in young patients, between 10 and 30 years of age, rep-
resenting 70% of ovarian neoplasms in this age group [83]; after menopause, malig-
nant ovarian germ cell tumors are very rare, while mature teratomas are uncommonly
seen [82, 84].
11 The Female Urogenital System in Geriatric Patients 285

b c

Fig. 11.7 Clear cell ovarian carcinoma. (a) Color Doppler US showing a unilocular cyst (*) with
solid protrusions (arrows) into the lumen, demonstrating high signal. (b, c) Axial contrast-­
enhanced CT showing enhancing nodules (arrows, b) and the infiltration of the sigma (arrow, c)

• Benign cystic mature teratomas are the most common germ cell tumor of the
ovary, composed of mature tissue of ectodermal, mesodermal, and endodermal
origin [48]. Therefore, hairs, skin glands, bone, cartilage, fat, and muscles may be
present within the mass. Monodermal tumors of the ovary, such as struma ovarii
or carcinoid tumors, also exist [48]. The US appearance is usually non-specific,
appearing as a predominantly cystic, solid, or complex mass with reflections and
shadowing. Findings vary from the classic presence of a so-called Rokitansky
nodule (cystic lesion with a densely echogenic tubercle projecting into the cyst
lumen), to an atypical diffusely or partially echogenic mass with sound attenua-
tion, due to the presence of sebaceous material and hair within the cavity, to mul-
tiple thin echogenic bands due to hairs. Fluid-fluid levels can result from the
separation of the sebum, which appears more hypoechoic than the fluid layer.
Shadowing may be present due to calcific or tooth components [48, 85]. At MRI,
286 M. A. Cova et al.

the tumor appears heterogeneous, with the sebaceous component being

T1-hyperintense, with a signal intensity similar to retroperitoneal fat and a T2
signal intensity similar to fat in most cases The lesion will show signal loss on
fat-saturated T1-weighted images or in the out-of-phase chemical shift sequence
[75], which allows the differential diagnosis with other lesions having high T1
and T2 signal intensities (hemorrhagic cysts or endometriomas) [48, 65].
Calcifications will show low signal intensity on T1- and T2-weighted images
(Fig. 11.8). At CT, fat can be easily recognized; wall calcifications or dermoid
plug may also be present [75] (Fig. 11.9). Complications of ovarian teratomas
may be torsion, rupture, or degeneration [86]. Mature teratomas can undergo
malignant degeneration in 1–2% of cases [86], although this rate increases in
post-menopausal women, with a study reviewing 20 cases of mature cystic terato-
mas in post-menopausal women reporting an incidence of malignant change of
15% [87]. Contrast enhancement of a Rokitansky nodule raises the possibility of
malign transformation; however, this finding does not always indicate malig-
nancy [88].

Sex-Cord Stromal Tumors

Sex-cord stromal tumors can affect patients from a broad range of ages [89]. They
account for about 8% of ovarian tumors, are mostly confined to the ovary at the time
of diagnosis, and may have hormonal activity [89]. They include pure stromal
tumors (e.g., thecomas, fibromas, fibrothecomas, and sclerosing stromal tumors),
pure sex-cord tumors (e.g., granulosa cell tumor), and mixed sex cord-stromal
tumors (e.g., Sertoli–Leydig cell tumor) [69]. Sclerosing stromal tumors and
Sertoli–Leydig cell tumors are rare and occur predominantly in patients of a younger
age [67].

• Granulosa cell tumors are the most common ovarian tumors to produce estrogens
and the most common malignant sex cord-stromal tumor [90]. The adult form
represents 95% of them and occurs mostly in perimenopausal and post-­
menopausal patients [89], with an incidence peaking at 50–55 years [91]. The
imaging characteristics are non-specific, as they may appear as a solid mass, a
tumor with hemorrhagic or fibrous components, or may be multilocular cystic or
entirely cystic tumors [67]. The multilocular cystic pattern with solid compo-
nents is the most common one, often resulting in a typical sponge-like appear-
ance on T2-weighted sequences [89]. For their hormonal production, endometrial
hyperplasia, endometrial polyps, or endometrial carcinoma can co-occur in
3–25% of cases [90]. Peritoneal dissemination is not frequent [67].
• Fibromas, fibrothecomas, and thecomas are a spectrum of benign tumors ranging
from purely fibrotic to lipid-rich tumors generally occurring in peri- and post-­
menopausal patients [89, 92]. Due to their fibrotic component, fibromas have a
11 The Female Urogenital System in Geriatric Patients 287

a b

c d

e f

Fig. 11.8 Teratoma. On T1-weighted (a) and T2-weighted images (b), the tumor (*) appears
heterogeneously hyperintense, with a signal intensity similar to retroperitoneal fat, and it contains
T2-hyperintense and T1-hypointense septa (black arrows). The lesion shows loss of signal on fat-­
saturated T1-weighted imaging (c). On the T1-weighted (d) and T2-weighted images (e) on a dif-
ferent plane, the so-called Rokitansky nodule (white arrows) can be appreciated. It appears
T1-hypointense and T2-hyperintense, with mild enhancement on fat-saturated contrast-enhanced
T1-weighted images (f, coronal plane)
288 M. A. Cova et al.

Fig. 11.9 Teratoma. Axial

CT scan showing a solid,
heterogeneous, ovoid mass
in the left adnexa, with
adipose density (asterisk)

homogenous solid appearance with delayed enhancement on CT [67] and have

low T1 and very low T2 signal intensity on MRI, with high-intensity areas due to
edema and cystic degeneration that may be present [67, 75, 93]. They have low
signal intensity on DWI sequence and only minimal enhancement after contrast
administration [65, 71, 75] (Fig. 11.10). At US, they appear as hypoechoic
masses with sound attenuation; however, findings are variable and sometimes
they can be seen as hyperechoic masses with increased through transmission
[70]. Uncommonly, they are associated with Meigs’ syndrome (ovarian tumor,
ascites, pleural effusion) [92]. The imaging appearance of thecomas is not spe-
cific and, especially if the fibrotic component is not prominent, they can be simi-
lar to malignant tumors [71, 89]. The differential diagnosis of these tumors
includes other fibrous-rich ovarian lesions (Brenner tumors, cystadenofibroma)
and pedunculated uterine leiomyomas [46].

11.2.3 Adnexal Torsion

Adnexal torsion is the twisting of an ovary, and often the fallopian tube, on their
ligamentous support, that may result in compromised blood flow [94]. It constitutes
a gynecological emergency requiring surgery, presenting with acute onset, intense,
and progressive pain, which in post-menopausal women may be continuous and
dull rather than acute and sharp [95, 96]. Adnexal torsion frequently is a complica-
tion of ovarian cysts and tumors [97], and most cases occur in pre-menopausal
patients because of the increased frequency of benign cysts and teratomas. It may
occur after menopause, although the incidence is low [95]. While the rate of malig-
nancy in younger patients is believed to be low, in post-menopausal patients, torsion
is more frequently associated with a malignant mass, but this occurs in a relative
minority of cases [95, 98].
11 The Female Urogenital System in Geriatric Patients 289

a b

c d

Fig. 11.10 Ovarian fibroma. (a–c) MRI showing a roundish mass in the left ovary, with very low
signal intensity on T2-weighted image (arrow, a) and low signal intensity on T1-weighted image
(arrow, b), with only mild enhancement after contrast administration (c), compatible with an ovar-
ian fibroma. (d) CT scan of a different patient showing a large solid abdominal mass with mild
enhancement and heterogeneous density (*), confirmed to be a fibroma after surgical excision

Imaging findings of ovarian torsion common to all modalities are an enlarged

ovary displaced supero-medially, a uterus displaced toward the affected side, a
thickened and twisted pedicle, a thickened tube, inflammatory changes surrounding
the involved adnexa with free pelvic fluid, and eventually a benign lead mass [98].
US is commonly the first imaging study performed and shows an enlarged, edema-
tous ovary in which the follicles are displaced peripherally [94]. The twisted pedicle
appears as a thickened tubular structure near the uterus and may show the “whirl-
pool sign,” that is, the twisting of the hypoechoic vessels, with or without a color
Doppler signal [98]. The findings of color Doppler analysis are variable: although
abnormal or reduced blood flow is a sensitive sign of torsion [99], normal vascular-
ity can be maintained until relatively late and should not exclude the diagnosis [98].
On CT and MRI, it appears as a mass located superiorly to the uterus and near the
midline [98]. Edema is seen as a hyperintensity of the central medulla on T2-weighted
images [98]. Features suggesting nonviability include hemorrhagic foci, which will
290 M. A. Cova et al.

appear hyperdense on CT and hyperintense on T1-weighted images and absent

enhancement [98]. Contrast-enhanced dynamic subtraction MRI can confirm the
absence of blood flow [100]. When the lead mass is a cyst, a smooth concentric cyst
wall thickening suggests simple edema, while an irregular or eccentric thickening
may indicate hemorrhagic infarction [97, 101].

11.2.4 Inflammatory Conditions of the Ovary

11.2.4.1 Tubo-Ovarian Abscess

Pelvic inflammatory disease is an uncommon condition in post-menopausal women,
and when it occurs it is usually polymicrobial and associated with the formation of
a tubo-ovarian abscess (TOA) [102]. US is the primary imaging modality for the
assessment of TOA, showing a cystic, solid, or complex mass in the adnexal or cul-­
de-­sac region, with adjacent fluid. Indistinct uterine margins and loss of midline
endometrial echoes may also be present [103]. CT can be useful to assess the extent
of the disease, presence of complications, and in case patients do not respond to
antibiotic therapy. Findings include a thick-walled hypodense adnexal mass with
internal septations and thickening of the uterosacral ligaments [104]. The pus-­
dilated tubes can be recognized as fluid-filled serpiginous structures with thick
enhancing walls. Internal gas bubbles are a specific sign of TOA but are rarely
observed. The rectosigmoid colon and ureter can be involved by the inflammatory
process [105]. On MRI, it appears as a mass heterogeneously hyperintense on
T2-weighted images and hypointense on T1-weighted images if the content is fluid,
but the imaging appearance depends on the hemorrhagic content and protein con-
centration. Fat-suppressed T2-weighted images are used to assess parametrial
inflammation, which appears as a hyperintense edematous area [105–107]. Contrast-­
enhanced fat-suppressed T1-weighted sequences are used to assess the extension of
inflammation and may show peritoneal enhancement [106]. Fibrosis and adhesions
may be present, appearing as T2-hypointense meshlike strands in the adjacent fat
with contrast enhancement [107]. There is considerable overlap in the imaging
appearance of TOA with that of other complex cystic masses, including neoplasms
and abscesses of non-gynecological origin [105].

11.3 Uterus and Cervix

11.3.1 Nabothian Cysts

A nabothian cyst is a mucus-filled cyst located usually on the surface of the cervix
[3]. On TVUS, it usually appears as an anechoic well-defined cystic lesion, with no
signal on color Doppler imaging [108], whereas, on non-contrast CT, it may appear
as a low attenuation formation. It is usually hyperintense on T2-weighted images,
while on T1-weighted images it appears as an intermediate or hyperintense lesion
because of its proteinaceous component and does not show enhancement after con-
trast administration [109, 110] (Fig. 11.11).
11 The Female Urogenital System in Geriatric Patients 291

a b

Fig. 11.11 Nabothian cyst (arrows). On gray-scale TVUS (a), a Nabothian cyst appears as an
anechoic well-defined cystic lesion, whereas it appears hyperintense on the axial T2-weighted MR
image (b)

11.3.2 Adenomyosis

Adenomyosis is defined as the ectopic presence of endometrial stroma and glands

within the myometrium, associated with surrounding hyperplasia and hypertrophy
of the myometrium. It can appear as a diffuse form, if less than 25% of the lesion is
surrounded by normal myometrium, or as a focal form (adenomyoma), if more than
25% of the lesion is surrounded by normal myometrium [111, 112]. Although the
histological exam is the gold standard for the diagnosis of adenomyosis, a non-­
invasive diagnosis can also be possible with TVUS and MRI. On TVUS, seven
items should be evaluated for the assessment of adenomyosis:

• its presence, according to the MUSA (Morphological Uterus Sonographic

Assessment) criteria: enlarged globular uterus, asymmetrical thickening of the
myometrium, myometrial cysts, echogenic subendometrial lines and buds,
hyperechogenic islands, fan-shaped shadowing, interruption of the junctional
zone, and high signal intensity on color Doppler imaging may be present because
of an increased vascularity,
• its location (anterior, posterior, lateral left, lateral right, or fundal), evaluated in
the sagittal and transverse plane,
• the differentiation between focal and diffuse disease,
• the evaluation of non-cystic or cystic adenomyosis, if there is at least a cyst with
largest diameter of more than 2 mm,
• the evaluation of myometrial involvement and serosa,
• the disease extension (mild, if less than 25% of the uterus is affected; moderate,
if between 50% and 75% of the uterus is affected; severe, if more than 50% of
the uterus is affected),
• the size of the lesion [111, 113].

On MRI, the diffuse form and the focal form of adenomyosis can be also evalu-
ated. The former presents itself with increased uterine dimensions (Fig. 11.12a). On
T2-weighted images, ill-defined hypointense foci, because of muscular hyperplasia
292 M. A. Cova et al.

a b

Fig. 11.12 Diffuse form of adenomyosis in a bicornuate uterus (a) and focal form of adenomyo-
sis (b, c). (a) Axial T2-weighted image showing increased uterine dimensions, ill-defined hypoin-
tense areas, due to muscular hyperplasia and hypertrophy, mildly hyperintense foci consisting of
ectopic endometrium, and markedly hyperintense cystic foci. Less than 25% of the lesion is sur-
rounded by normal myometrium. (b, c) In a different patient, axial (b) and sagittal (c) T2-weighted
images showing a hypointense mass-like formation (arrows) in the myometrium with hyperintense
cystic area (arrowheads). More than 25% of the lesion is surrounded by normal myometrium

and hypertrophy, and multiple hyperintense foci, consisting of ectopic endome-

trium, can be seen. On T1-weighted images, the areas of adenomyosis have the
same signal intensity compared to the surrounding myometrium, but sometimes
hyperintense hemorrhagic areas can be present in zones with ectopic presence of
endometrial stroma and glands [110, 114–116]. The focal form appears as a hypoin-
tense mass-like formation in the myometrium on T2-weighted images, and hyperin-
tense areas can also be present [110] (Fig. 11.12b, c).
Sometimes the differential diagnosis between adenomyosis and leiomyomas
may be difficult; nevertheless, the latter usually have well-defined margins, a pseu-
docapsule, and greater mass effect than the former [114, 117, 118].

11.3.3 Polyps

Polyps are benign lesions occurring in both perimenopausal and post-menopausal

women [110, 119]. They consist of endometrial glands, fibrotic components, and
vessels and can be sessile or pedunculated, usually located in the uterine fundus
[120]. On TVUS, a polyp may appear hypoechoic or hyperechoic [121] (Fig. 11.13),
11 The Female Urogenital System in Geriatric Patients 293

a b

Fig. 11.13 Cervical (a) and endometrial (b) polyps. (a) Gray-scale TVUS showing a hypoechoic
pedunculated cervical polyp (between calipers). (b) Gray-scale TVUS showing a mildly
hypoechoic endometrial polyp with hyperechoic periphery (between calipers)

whereas, on T2-weighted MR images, it appears slightly hypointense compared to

the endometrium and may have a hypointense fibrous core [117]. It also shows
higher ADC values compared to endometrial carcinoma [122]. Sometimes the dif-
ferential diagnosis between a polyp and a submucosal leiomyoma may be difficult;
nevertheless, the latter usually originates from the myometrium and has lower sig-
nal intensity on T2-weighted images [110, 119].

11.3.4 Leiomyomas

Leiomyomas are the most frequent uterine benign disease, occurring in about
20–30% of young women, usually regressing in post-menopausal women [64, 123].
Leiomyomas, generally affecting the body of the uterus and more rarely the cervix,
are uterine smooth muscle benign neoplasms that may also contain connective tis-
sue and have a pseudocapsule [119, 123]. They can be divided depending on their
location into: submucosal (in the subendometrial zone), intramural (within the myo-
metrium), subserosal (in the subserosal zone), or cervical (in the cervix) [110, 123].
On TVUS, leiomyomas may appear as well-defined lesions hyperechoic or
hypoechoic compared to the myometrium; they may show shadowing near and
within the formation, and calcifications with distal shadowing may also be present
(Fig. 11.14a). On MRI, leiomyomas can be appreciated as solid roundish forma-
tions with sharp borders [124]. Besides standard T1-weighted and T2-weighted
sequences of the female pelvis, additional coronal and axial oblique perpendicular
to the long axis of the uterus T2-weighted sequences are helpful to accurately local-
ize the lesions and to confirm their uterine origin. On T1-weighted sequences, they
can be hardly distinguished because they show intermediate signal intensity similar
to myometrium [119, 123], whereas, on T2-weighted images, they usually show
low signal intensity or slightly high signal intensity in case of high cellularity and
may have a hyperintense pseudocapsule [123] (Fig. 11.14b). When fat is present,
leiomyomas are called lipoleiomyomas, and they appear as high signal intensity
lesions on both T1 and T2-weighted images [110] (Fig. 11.15). After contrast
294 M. A. Cova et al.

a b

Fig. 11.14 Leiomyoma. (a) Gray-scale TVUS showing a large, well-defined subserosal leiomy-
oma (arrow). (b) Sagittal T2-weighted MR image in the same patient confirming the leiomyoma
(arrow), showing the typical hypointense signal

a b

Fig. 11.15 Lipoleiomyoma (*). It appears hyperintense on T2-weighted image (a) and on
T1-weighted image (not shown). The lesion shows loss of signal on fat-saturated T1-weighted
image (b) and no enhancement on fat-saturated T1-weighted image after contrast administration (c)
11 The Female Urogenital System in Geriatric Patients 295

administration, their behavior may vary depending on their cellularity [125].

Leiomyomas, particularly if large, may undergo degeneration, showing different
appearances depending on the type of degeneration: red, cystic, myxoid, hyaline, or
calcific [110, 123, 126]. Red degeneration shows T1-hyperintensity and variable
signal intensity on T2-weighted images, while cystic degeneration is characterized
by high signal intensity on T2-weighted sequences. Both types do not usually show
enhancement, differently from myxoid degeneration, which also appears hyperin-
tense on T2-weighted images and hypointense on T1-weighted images [64, 110].
Hyaline degeneration is characterized by low signal intensity on T2-weighted
sequences and intermediate signal intensity on T1-weighted sequences [110].
Moreover, in the end-stage, leiomyomas may undergo calcific degeneration, show-
ing signal void in all sequences [126] (Fig. 11.16).
Malignant evolution is quite rare and has to be suspected in case of a leiomyoma
increasing rapidly in size or with irregular borders [125, 127, 128]. When the tumor
shows an aggressive behavior, MRI can be used to assess the involvement of the
surrounding organs and lymph nodes [129]. However, it is not possible to certainly
differentiate large degenerated leiomyomas from leiomyosarcomas based on the
signal characteristics on MRI [123] (Fig. 11.17). Leiomyosarcomas usually show
low signal intensity on T1-weighted images and intermediate/high signal intensity
on T2-weighted images; the diagnosis of leiomyosarcoma may be suggested by
nodular borders, hemorrhage, T2-weighted dark areas, and central foci without
enhancement [64]. The solid components of the lesion are associated with necrosis,
showing high signal intensity on T2-weighted sequences, and are usually character-
ized by early enhancement after contrast administration. In addition, leiomyosar-
coma usually shows high signal intensity on DWI and low signal intensity on
ADC. Nevertheless, restricted diffusion on DWI may not help in the differential
diagnosis with leiomyomas, which also can show restricted diffusion on DWI
because of their high cellularity [126, 129].

a b

Fig. 11.16 Calcific leiomyoma. Gray-scale TVUS showing an end-stage leiomyoma (black
arrow, a and between calipers, b) with calcific degeneration (arrowheads) and distal shadowing
(white arrows)
296 M. A. Cova et al.

a b

Fig. 11.17 Large degenerated leiomyoma. Coronal (a) and sagittal (b) T2-weighted images
showing a large degenerated intramural leiomyoma. Some components show high signal on DWI
(arrow, c). In this case, it is not possible to certainly differentiate this large degenerated leiomyoma
from leiomyosarcoma based on MR imaging. Nevertheless, the absence of nodular borders, hem-
orrhage, T2-weighted dark areas, and central foci without enhancement is suggestive of a large
degenerated leiomyoma

11.3.5 Endometrial Carcinoma

Endometrial carcinoma (EC) is estimated to be the most common gynecologic

malignancy in western countries, ranging from 4 to 8%, with a maximal incidence
in post-menopausal women [130].
EC arises from endometrial glands and can be focal or diffuse [131]. It can be
divided into two types: type I (grade 1 and 2 endometrioid carcinoma), usually
affecting perimenopausal women, is characterized by estrogen dependency and
good prognosis, while type II (grade 3 endometrioid carcinoma and cancers of non-­
endometrioid histology), occurring in post-menopausal women, is characterized by
non-estrogen dependency and poor prognosis [122, 132, 133]. The most common
risk factors of EC are nulliparity, obesity, diabetes, hypertension, polycystic ovary,
older age, late-onset menopause, early menarche [130, 134, 135]. The most frequent
presenting symptom is abnormal uterine bleeding [130].
11 The Female Urogenital System in Geriatric Patients 297

TVUS should be the first imaging choice in older women with abnormal bleed-
ing to measure the endometrial thickness. An upper threshold of 5 or 4 mm is con-
sidered as the cut-off of normality in these patients [133].
Although the staging of EC, which follows the International Federation of
Gynecology and Obstetrics (FIGO) criteria [132], depends on surgical and histo-
pathological findings, MRI, thanks to its contrast resolution, can be an important
tool in the preoperative staging of the EC [122, 136].
According to current guidelines, the dedicated MRI protocol should include an axial
oblique perpendicular to uterus corpus T2-weighted sequence for an accurate evaluation
of the depth of myometrial invasion, an axial oblique DWI sequence to match the
T2-weighted sequence, and a T1- or T2-weighted sequence up to the renal hilum for
lymph nodes and hydronephrosis. In case of grade 3 endometrioid adenocarcinoma or
non-endometrioid carcinomas, an axial DWI sequence to match the sequence for lymph
nodes and hydronephrosis should be added. In addition, contrast-enhanced images
acquired after two and a half minutes should be usually performed [10].
EC is stage IA (Fig. 11.18) in case of a tumor confined to less than half of the
myometrium, whereas it becomes stage IB (Fig. 11.19) in case of involvement of

a b

Fig. 11.18 Endometrial cancer, FIGO stage IA: A tumor (arrow) confined to less than half of the
myometrium can be appreciated on the sagittal T2-weighted image (a), DWI image (b), and fat-­
suppressed T1-weighted contrast-enhanced image, on which it appears hypointense, being hypo-
vascular compared to the normal myometrium (c)
298 M. A. Cova et al.

a b

c d

Fig. 11.19 Endometrial cancer, FIGO stage IB. A tumor (asterisk) within the uterine lumen,
hyperintense on T2-weighted image (a) and hypointense being hypovascular compared to the
myometrium on the contrast-enhanced image with fat suppression (b), involving more than half of
the myometrium (arrow, b), can be appreciated. The lesion shows restricted diffusion, with high
signal intensity on DWI (c) and low signal on the ADC map (d)

more than half of the myometrium [136, 137]. Stage II EC is a tumor involving the
hypointense stroma of the cervix. A dynamic contrast-enhanced T1-weighted
sequence may be useful in the evaluation of difficult cases; indeed, if the enhance-
ment of the cervical mucosa is conserved in the delayed phase, the presence of
stromal infiltration can be excluded [136]. EC is stage III if the lesion interrupts the
outer contour of the uterus; EC in this stage remains confined to the true pelvis [136,
137]. EC is stage IVA in case of invasion of the vesical or rectal mucosa. This can
be excluded with high accuracy in case of preservation of the fat planes between the
lesion and bladder or rectum. When distant metastases are present, EC becomes
stage IVB [122, 136, 137] (Fig. 11.20).
11 The Female Urogenital System in Geriatric Patients 299

a b

Fig. 11.20 Endometrial cancer, FIGO stage IVB. A tumor involving less than half of the myome-
trium can be appreciated on the sagittal T2-weighted image (arrow, a). Axial T2-weighted imaging
(b) shows a peritoneal metastasis in the right iliac fossa (white arrow, b and c), which has high
signal intensity on DWI (c). The staging was histologically confirmed after hysterectomy

MRI can also be useful in the evaluation of myometrial and cervical stromal
invasion [136]. On T1-weighted sequences, EC usually appears as a lesion isoin-
tense to the myometrium [137], whereas, on T2-weighted images, it appears as a
diffuse or well-delineated mass with heterogeneous intermediate signal intensity,
higher than the hyperintense endometrium and lower than the hypointense myome-
trium [122, 136].
On post-contrast T1-weighted images, the lesion shows an early enhancement
compared to the surrounding endometrium and slow enhancement compared to the
myometrium, appearing hypointense compared to the myometrium in the late phase
[122]. Post-contrast T1-weighted sequences can play a key role in the evaluation of
the infiltration of the cervical stroma and the myometrium. In case of EC confined
to the endometrium, a continuous enhancement of the subendometrial zone can be
seen, whereas a disruption of this zone can be present in case of myometrial inva-
sion [136].
EC shows restricted diffusion on DWI due to increased cellularity. Indeed, DWI
increases the capability of detecting EC, in particular smaller ones, and can be use-
ful in the assessment of the infiltration of the myometrium and the cervical stroma;
DWI also improves the identification of metastases in the vagina, cervix, adnexa,
and peritoneum [122, 136, 137].
300 M. A. Cova et al.

DWI is sensitive but not specific for the identification of malignant lymph nodes
because reactive lymph nodes also show high signal intensity on this sequence.
Therefore, a size threshold of 10 mm in short axis diameter for para-aortic nodes
and 8 mm for pelvic ones is used to define neoplastic infiltration. Round shape,
spiculated margins, heterogeneous signal intensity, or necrosis are other morpho-
logic patterns suggesting tumor involvement [122, 136, 137].
After therapy, diffusion-weighted and post-contrast T1-weighted sequences can
also be used to differentiate the inflammation after radiotherapy from recur-
rence [122].
Sometimes the differential diagnosis between EC and uterine polyps or endome-
trial hyperplasia can be difficult: DWI may be a useful tool in these cases because
the ADC value of normal endometrium and polyps is significantly higher than
EC. Nevertheless, also hyperplastic endometrium may show low ADC values like
EC. Blood products may also show low ADC values; a careful evaluation of
T1-weighted images is important to confirm this finding. In addition, the evaluation
of T2-weighted images can be useful for the differential diagnosis between EC and
a leiomyoma mimicking an endometrial thickening because leiomyomas appear
hypointense on this sequence [112].

11.3.6 Squamous Cell Carcinoma of the Uterine Cervix

Cervical cancer (CC) is the fourth most frequent neoplasm in women, with an aver-
age age of 53 years at diagnosis [138]. Patients usually present with vaginal bleed-
ing and discharge [139, 140]. Various risk factors are associated with CC, including
young age at first sexual intercourse, multiple sexual partners, sexually transmitted
viral infections (HPV, HSV2), and multiparity [140–142]. CC usually arises from
the transformation zone, between the ectocervix and the endocervix [143]. The
most common cancer histotypes are adenocarcinoma and squamous cell carcinoma
(up to 89% of cases) [140]. Dysplasia, which can be divided into mild, moderate,
and severe, precedes the development of neoplasia, which is defined as preinvasive
(cervical intraepithelial neoplasia, CIN) if the basement membrane is not involved,
and as invasive in case of penetration of the basement membrane and involvement
of stroma of the cervix.
Staging is obtained according to the FIGO system [132]. While TVUS is an
important tool for the initial evaluation of EC, evidence supporting its use in CC is
weak because the parametrial involvement cannot be surely assessed on
11 The Female Urogenital System in Geriatric Patients 301

transvaginal ultrasonography. CT is a rapidly acquired exam with high spatial reso-

lution, but it has lower soft-tissue contrast than MRI and it is usually not adequate
for the differentiation between CC and normal cervical stroma or parametria. In
contrast, MRI is the imaging method of choice for staging and restaging CC because
of its high soft-tissue contrast on T2-weighted images [139, 144]. On this sequence,
CC appears as an intermediate/high signal intensity mass within the hypointense
cervical stroma [137]. The most adequate plan to evaluate enhancement in the cer-
vix is the sagittal one [10]. On post-contrast T1-weighted sequences, small CC usu-
ally shows an early homogeneous enhancement, while large ones show a
heterogeneous enhancement because of necrotic components [145]. Nevertheless,
there is no consensus in the literature about the use of intravenous contrast agents
for CC staging [137, 144].
DWI images may be useful in detecting small tumors because CC usually shows
high signal intensity on DWI and low signal intensity on ADC; indeed, CC reveals
statistically significant lower ADC values compared to the normal cervix [137].
CC is stage IA in case of a tumor not detectable on MRI [146], while it is stage
IB if an intermediate/high signal intensity lesion is seen within the hypointense
stroma of the cervix on T2-weighted images. CC is a stage IIA tumor if it involves
the low signal intensity of the upper two-thirds of the vagina, whereas it is stage IIB
if there is infiltration of the parametria, appearing as a disruption of the hypointense
cervical stroma ring [122, 137]. In this case, an evaluation in the oblique plane per-
pendicular to the endocervical canal longitudinal axis is mandatory to detect para-
metrial invasion. On this plane, a T2-weighted sequence and a late phase acquisition
after contrast should be usually done. In stage IIIA, CC involves the lower third of
the vagina, and in stage IIIB, it infiltrates the pelvic wall or the ureters. CC is stage
IV when it has extended beyond the true pelvis or has involved the rectal or bladder
mucosa (Fig. 11.21). On T2-weighted images, the organ involvement appears as a
focal disruption of the hypointense muscular layer of the bladder or rectum by the
hyperintense CC. Also post-contrast T1-weighted sequences can be useful in evalu-
ating tumor infiltration because CC usually shows stronger enhancement than the
muscular layer [139].
302 M. A. Cova et al.

a b

c d

e f

Fig. 11.21 Cervical cancer, FIGO stage IV. Gray-scale TVUS (a) showing a hypoechoic cervical
lesion (between calipers). Contrast-enhanced axial CT scan (b) showing the cervical cancer
involving the posterior wall of the bladder (black arrow). Note the dilation of the right ureter, better
shown on curvilinear sagittal reconstructions (white arrow, c), secondary to the infiltration of the
right ureteral meatus. Axial (d) and sagittal (e) T2-weighted images showing the cervical cancer
involving the bladder; the organ involvement appears as a focal disruption of the hypointense mus-
cular layer of the bladder (arrow, e). The post-contrast axial T1-weighted sequence (f) is useful in
the evaluation of tumor infiltration because the lesion usually shows stronger enhancement than
the muscular layer; note also the involvement of the anterior wall of the rectum (arrow, f)
11 The Female Urogenital System in Geriatric Patients 303

11.4 Vagina and Vulva

11.4.1 Malignant Tumors of the Vagina

11.4.1.1 Primary Tumors

For a tumor to be considered a primary vaginal cancer, it must originate from the
vagina, with no involvement of the external os superiorly and the vulva inferiorly,
and with no clinical or histological evidence of cervical or vulvar cancer or a prior
history of these tumors within 5 years [147]. Tumors that extend to the external os
are classified as cervical cancer, and vaginal tumors occurring within 5 years from
a malignant cervical or vulvar cancer are considered recurrences of these tumors
rather than a new primary malignancy [148, 149].
Primary vaginal cancer is a rare entity, constituting about 10% of vaginal cancers
and 1–2% of gynecological malignancies [150]. The incidence of the disease
increases with age, with about 50% of patients presenting after 70 years of age
[151]. The most common cancer histotype is squamous cell carcinoma (90%),
which is typical of an older age and is frequently associated with HPV; other risk
factors are a history of previous cervical or vulvar carcinoma [152]. Adenocarcinoma
(9%) is not typical of post-menopausal patients, occurring in much younger women
(mean age 19 years) [151]. The remaining primary vaginal cancers are melanomas,
sarcomas, and lymphomas [148].
Patients may be asymptomatic or may present with painless vaginal bleeding,
vaginal discharge, urinary tract symptoms, pelvic pain, or a pelvic mass [153]. At
clinical examination, it may appear as an ulcerating lesion, a fungating mass, or an
annular constricting mass [152].

Imaging Findings of Vaginal Squamous Cell Carcinoma

The diagnosis of primary vaginal cancer is obtained clinically by biopsy. Staging is
clinical as well and follows the American Joint Committee on Cancer TNM staging
and the FIGO system [154, 155].
Imaging should not be used to change the clinical staging; however, FIGO rec-
ommends cross-sectional studies to better define the tumor volume and extension of
the disease, in order to guide management. Specifically, MRI is more sensitive in
detecting the tumor size and the paravaginal and parametrial involvement and can
also be used in individual cases when the clinical assessment of the tumor is difficult
[148]. MRI is also useful to evaluate for local recurrences after therapy. Contrast-­
enhanced CT is used to detect distant metastases and lymph node spread. US can be
used to evaluate inguinal nodes and to guide biopsy, if necessary [10].
The MRI protocol to study vaginal cancer should include at least T2-weighted
images of the pelvis in the axial, sagittal, and axial oblique (perpendicular to the
long axis of the vagina) plane and axial T1-weighted and DWI sequences of the
pelvis. The use of endovaginal gel and obtaining axial pre- and dynamic contrast-­
enhanced T1-weighted fat-saturated images of the pelvis and sagittal contrast-­
enhanced T1-weighted fat-saturated sequences are optional [10].
304 M. A. Cova et al.

The squamous cell vaginal carcinoma occurs more commonly in the upper third
of the vagina, on the posterior wall, and can appear as a diffuse mass with ill-defined
and irregular margins, as a well-defined lobulated mass, or as a circumferential
thickening [152, 156]. The tumor is best assessed on T2-weighted images, on which
it shows an intermediate signal intensity, which is distinguished from the low inten-
sity of the vaginal wall. On T1-weighted images, it is isointense to muscles and can
be identified only when large enough to alter the contour of the vagina [152].
Vaginal cancer spreads by direct extension to the surrounding pelvic organs,
including paravaginal tissue, parametria, urethra, bladder, and rectum [148]. If the
T2-hypointensity of the outer layer of the vaginal wall is preserved, the tumor is
limited to the mucosa and is a stage I; when the wall hypointensity is disrupted,
the tumor has extended to the paravaginal tissues and is stage II. The extension
through the vaginal wall is best assessed on the oblique axial plane. A stage III
tumor involves the pelvic sidewalls, which are best assessed on axial and coronal
planes, and it is seen as a higher T2-signal intensity within the muscles due to
edema or direct tumor invasion. In stage IVA, the cancer involves the mucosa of
the rectum or bladder, and direct infiltration with loss of the normal hypointensity
of the bladder and rectal walls as well as loss of the vesicovaginal fat plane or
rectovaginal septum is appreciated. Bullous edema may be difficult to differenti-
ate from tumor infiltration and may result in overstaging. A stage IVB tumor
spreads to distant organs, and lungs, liver, and bones are commonly involved sites
[151, 152, 155] (Fig. 11.22).
The lymphatic spread of the tumor is complex and is often present, even in ear-
lier stages (6–14% in stage I, 26–32% in stage II) [156, 157]. In general, upper vagi-
nal tumors drain to pelvic lymph nodes, including obturator, internal and external
iliac lymph nodes; involvement of para-aortic nodes is rare. The lower vagina drains
to inguinal and femoral lymph nodes. The middle third of the vagina can follow
either route. Posterior wall lymphatics drain to the inferior gluteal, sacral, and rectal
nodes [148, 152].
After treatment, recurrences are most commonly seen within the first 2 years.
Tumors of the upper third tend to recur locally, while lower tumors are more
often associated with pelvic sidewalls invasion or distant recurrences [151, 152].
MRI is useful in differentiating residual tumor from post-treatment changes
although it may be difficult, especially in the few months after treatment, when
T2-hyperintense edema is also present. In time, the scar tissue appears T2
hypointense, while the tumor has T2-intermediate to high signal intensity and
enhances avidly [151].
Complications after treatment generally occur within 5 years, but they may be as
late as 20 years and are due to radiation-induced bladder, vaginal, and rectal toxic-
ity. They include cystitis, proctitis, bowel stricture and perforation, bone osteone-
crosis, and stress fractures [151, 158]. Common complications are rectovaginal and
vesicovaginal fistulas, best demonstrated on axial or sagittal high-resolution
T2-weighted or short tau inversion recovery (STIR) sequences, where they appear
as a tract with fluid hyperintensity and air hypointensity [151, 152].
11 The Female Urogenital System in Geriatric Patients 305

a b

c d

Fig. 11.22 Vaginal cancer. Axial T2-weighted sequence (a), axial fat-suppressed sequence (b),
and fat-suppressed contrast-enhanced T1-weighted sequences on the axial (c) and sagittal (d)
plane, showing a prevalently exophytic mass (white arrow, a) with spiculated margins, involving
the postero-lateral fornix and the postero-lateral region of the cervix on the left. The mass infil-
trates the adjacent adipose tissue and the left uterosacral ligament, and it infiltrates the rectal serosa
at 2 o’ clock (black arrow, a). Note the right presacral small lymph node with irregular margins
(arrow, c). According to FIGO staging, this is a stage IV tumor

11.4.1.2 Secondary Tumors

Most vaginal malignancies are secondary tumors, accounting for more than 80% of
vaginal cancers [148]. Most malignant tumors of the vagina are due to secondary
involvement by adjacent tumors, but lymphatic or hematogenous metastatic spread
from distant cancers can also occur. The primary tumors most frequently metasta-
sizing to the vagina are ovarian, cervical, endometrial, and rectal cancer, but also
vulvar and bladder carcinoma can involve the vagina. Only very rarely vaginal
metastases from other extra-genital cancers, e.g., colon, breast, pancreas, small
306 M. A. Cova et al.

bowel, occur [152]. In general, the MR features of vaginal metastases mimic the
primary tumor [152].

11.5 Vulva

11.5.1 Malignant Tumors of the Vulva

Vulvar cancer accounts for 2% to 5% of gynecological malignancies peaking in the

seventh decade, with about 66% of cases occurring after the age of 70 years; how-
ever, the mean age of occurrence is decreasing in the last years due to an increased
rate of HPV infection [20, 159]. The most common vulvar cancer is squamous cell
carcinoma (90%), followed by melanoma (5–10%) and basal cell carcinoma
(2–4%). Rarer occurrences are Paget’s disease (1–2%), affecting mainly post-­
menopausal women of a median age of 72 years, sarcoma, adenocarcinoma, and
Bartholin gland carcinoma. Metastases from other primary cancers constitute 5–8%
of vulvar malignancies [160].
In pre-menopausal women, vulvar squamous carcinoma is more likely to be
associated with HPV infection, while older patients often have vulvar dermatoses,
like lichen sclerosis. Clinically, many patients are asymptomatic; when symptoms
are present, they include pruritus, burning, pain, abnormal bleeding or discharge, or
the occurrence of a lump or an ulcer. It can appear as a warty or polypoid mass or a
raised, flat ulcerated plaque-like lesion at clinical examination.

11.5.1.1 Imaging Findings of Vulvar Squamous Cell Carcinoma

Diagnosis of vulvar cancer is usually made by clinical examination and biopsy
[159]. Imaging, and in particular CT and MRI, has a role especially in locally
advanced disease to identify the local extent of the tumor and the infiltration of
adjacent structures, to evaluate lymphadenopathies and distal metastases, and to aid
in surgical planning [159]. US may be useful to evaluate nodal involvement and to
guide biopsies. On US, the tumor appears as a soft-tissue mass with internal vascu-
larity [161, 162]. CT is not useful for local staging because of its low contrast reso-
lution, but it may identify the bladder or rectum involvement and can detect distant
metastases [163]. On CT, the tumor appears as a non-specific vulvar thickening or
mass with soft-tissue density [162].
Vulvar squamous cell carcinoma is staged according to the American Joint
Committee on Cancer TNM staging and the FIGO system. The FIGO staging was
11 The Female Urogenital System in Geriatric Patients 307

revised in 2009 and can be applied to most vulvar cancer except melanoma [159].
MRI is preferred for local staging. The exam is performed after bladder emptying,
and ultrasound gel may be used to distend the vagina to better assess vaginal wall
infiltration and possibly to identify smaller vulvar lesions. The protocol should
include axial T1-weighted FSE images with a large FOV to evaluate lymphade-
nopathies and bone marrow abnormalities; axial and coronal high-resolution
T2-weighted FSE sequences to evaluate the primary tumor; and sagittal dynamic
fat-saturated contrast-enhanced T1-weighted images with a small FOV for the
extent of tumor involvement. High-resolution axial T2-weighted FSE sequences
with a small FOV and 3-mm thick sections can be obtained through the perineum.
The tumor may be better appreciated on T2-weighted images with fat suppression
than non-fat saturated images, and contrast-enhanced sequences can help identify
small tumors and assess invasion of the urethra, anus, and vagina. Diffusion-­
weighted sequences can also be useful to assess the primary tumor and lymphade-
nopathies [163].
On MRI, the tumor has low signal intensity on T1-weighted images and
intermediate-­to-high signal intensity on T2-weighted images [20]. In two-thirds
of cases, the labia are involved, with the clitoris and Bartholin glands [20]
(Fig. 11.23). Small stage I cancers may be missed and stage I or II tumors with an
“en-plaque” aspect may also be difficult to identity on MRI [164]. The urethra,
anorectum, vagina, perineal muscles, and the bladder should be carefully assessed
for signs of infiltration, which will appear as a tissue of intermediate signal inten-
sity, in continuity with the primary tumor, within the hypointense muscular walls
of the urethra, vagina, and anorectum. T2-weighted images in the sagittal and
coronal planes could be helpful to assess the whole tumor if deep infiltration is
suspected [164].
The tumor spreads mainly by local invasion, followed by lymphatic spread and
hematogenous spread to distant organs (lung, liver, bone) [161]. Inguinal and femo-
ral lymph nodes are the first to be involved, followed by pelvic nodes [165]. Lymph
node involvement can be uni- or bilateral, depending on tumor size and its closeness
to the middle line [159].
The most important prognostic factors in vulvar cancer are tumor size, depth of
infiltration, and particularly the presence of lymph node metastases. Recurrences
can be local or distant and are generally seen within 2 years after initial treatment
[20] (Fig. 11.24).
308 M. A. Cova et al.

a b

c
d

e f

Fig. 11.23 Vulvar cancer. At the vaginal introitus, on the right side, there is a vulvar lesion (arrow,
a), with intermediate T2 signal intensity (a), restricted diffusion (b, c), and enhancement after
contrast administration (d). At the PET/CT (e–g), on the unenhanced CT, a paravaginal hypodense
tissue in the perineum can be recognized (arrow, e), and it shows an intense uptake of the
[18F]-fluorodeoxyglucose tracer (f), well-shown on the fusion imaging (g)
11 The Female Urogenital System in Geriatric Patients 309

a b

c d

e f

g
310 M. A. Cova et al.

Fig. 11.24 Locoregional recurrence of vulvar cancer. Patient with previous vulvectomy per-
formed 5 years before and a urinary catheter in place. At the vaginal introitus, there is a solid lesion
(black arrow, a), heterogeneously hypointense on T2-weighted sequences (a, b), that involves the
full thickness of the vaginal wall, extending cranially up to the middle vaginal third (b), and sur-
rounding the urethra in its inferior two-thirds (white arrow, a). The lesion shows restricted diffu-
sion (c, d) and a heterogeneous enhancement for the presence of central necrotic areas (e). At the
PET/CT scan, the lesion can be seen as a solid mass on the unenhanced CT images (arrow, f), with
an intense uptake of the [18F]-fluorodeoxyglucose tracer (g)

11.6 Pelvic Organ Prolapse

Functional disorders of the pelvic floor refer to a group of medical conditions affect-
ing the ligaments, fasciae, and muscles, supporting the pelvic organs [166]. These
conditions are relatively common and predominantly affect older women [167].
The appearance of the pelvic organs can be evaluated on MRI at rest and during
active contraction, the so-called Valsalva maneuver. A state-of-the-art MRI protocol
includes axial, coronal, and sagittal rapid half-Fourier T2-weighted imaging
sequences at rest; successively, six to eight rapid T2-weighted images are also
acquired during the Valsalva maneuver [168].
The pelvic floor can be divided into three anatomic compartments: the anterior,
the middle, and the posterior. In the anterior compartment there are the bladder and
the urethra, in the middle one the uterus, the cervix, and the vagina, in the posterior
one the rectum, the anus, and the anal sphincter. This paragraph will be focused on
the pathology of the middle compartment, while the pathology of the anterior and
the posterior ones will not be included in this chapter.
In the pelvic middle compartment, disorders include uterine or cervical prolapse.
Pelvic organ prolapse is the abnormal descent or herniation of the pelvic organs
through their respective hiatus due to failure of support structures and perineal hia-
tal weakening. Uterine prolapse is the uterine herniation beyond the vagina, caused
by a failure of the ligamentous and fascial supports (the pubocervical ligaments,
parametrium and paracolpium, uterosacral ligaments, rectovaginal fascia, and peri-
neal body). The laxity of the uterosacral ligaments contributes to an anterior move-
ment of the cervix with progressive uterine retroversion, causing the prolapse [168,
169]. Cervical prolapse can be seen as a bulging mass outside the external genita-
lia [168].
On MR defecography, it can be diagnosed when the cervix is located 1 cm below
the pubococcygeal line (PCL), a straight line connecting the inferior border of the
pubic symphysis to the last coccygeal joint [167]. The distance between the PCL
and the most anterior and inferior aspect of the cervix is used as reference for grad-
ing: a prolapse is considered small when the distance is less than 3 cm, moderate if
3 to 6 cm, and severe if over 6 cm [166]. In case of previous hysterectomy, the vagi-
nal apex should be at least 1 cm above the PCL line, using the most posterior and
superior aspect of the vaginal vault [166]. Vaginal vault prolapse is generally associ-
ated with other pelvic prolapses, most commonly an enterocele [170].
11 The Female Urogenital System in Geriatric Patients 311

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Osteoarthritis in Axial Skeleton
in Geriatric Patients 12
Francesca Serpi, Salvatore Gitto,
and Luca Maria Sconfienza

12.1 Degenerative Pathology

With the increase in life expectancy, degenerative pathologies of the spine are
becoming more and more common during clinical practice, with a high medical and
socioeconomic impact.
Degenerative changes in the spine are usually associated with back pain and/or
symptoms of neural structure compression, caused by anatomical and biomechani-
cal alterations.
Imaging the degenerative spine might be quite challenging. In fact, the presence
of symptoms and pain does not always correspond to abnormal findings at imaging,
as well as the presence of degenerative imaging changes does not necessarily cor-
relate with the presence and the severity of pain. In addition, sometimes it is not
easy to discriminate between imaging findings of normal aging and degenerative
pathology.
The spine is a multiarticular structure, which enables motions in different direc-
tions and absorbs multidirectional loads. Specifically, two adjacent vertebrae, the
intervertebral disc, spinal ligaments, and facet joints between them constitute a
functional spinal unit [1].
The main functions of the spine are to provide structural support, enable trunk
movement, and protect the neural elements [2].
Approximately 70% of applied axial compression is transmitted by the vertebral
body and the intervertebral disc, with the remaining 30% of the load being distrib-
uted through the facet joints (Fig. 12.1) [3].

F. Serpi · S. Gitto · L. M. Sconfienza (*)

Unit of Diagnostic and Interventional Radiology, IRCCS Ospedale Galeazzi-Sant’Ambrogio,
Milan, Italy
Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 319
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_12
320 F. Serpi et al.

Fig. 12.1 Schematic

representation of a
functional spinal unit.
Axial compression is
transmitted 70% by
vertebral body and the
intervertebral disc, 30% of
load is distributed through
the facet joints

Degenerative changes are considered an adaptive response to insults, such as

mechanical (micro or macro-insults) or metabolic injuries (chondrosis or muco-
polysaccharidoses), rather than a true disease [4].
In the majority of cases, degenerative changes are related to mechanic causes,
such as chronic micro-insults, trauma, and vertebral fractures or load redistribution
that occurs after spinal surgery.
It is important to notice that the pathogenesis of the degenerative process repre-
sents a biomechanically related continuum of anatomical alterations that evolves
over time [3]. A good knowledge of the pathophysiology of these biomechanical
changes in the spine is essential for radiologists to characterize radiological abnor-
malities. Therefore, degenerative changes should not be considered as an isolated
event or reported as a random finding. All elements of the spine, including the inter-
vertebral discs, facet joints, ligaments, and bony structures, may undergo morpho-
logical changes that can be classified as degenerative. However, in the majority of
cases the degenerative process starts within the nucleus pulposus and progresses to
the other elements of the functional spinal unit (horizontal or segmental degenera-
tion) [5–7], such as the annulus fibrosus, endplates, and bone marrow of the adja-
cent vertebral bodies. Advanced degeneration may eventually lead to facet joint
osteoarthrosis, ligamentum flavum hypertrophy, and spinal canal stenosis [3].
Degenerative changes can also alter the entire biomechanics of the spine, includ-
ing the adjacent functional spinal units (adjacent segment disease) [8, 9].
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 321

12.2 Functional Spinal Unit

12.2.1 Intervertebral Disc

12.2.1.1 Anatomy and Pathophysiology

Intervertebral discs are located between adjacent vertebral bodies, acting as shock
absorbers. They are complex structures composed of nucleus pulposus, annulus
fibrosus, cartilaginous endplates, and vertebral body ring apophyseal attachments of
the annulus [10]. The intervertebral disc is mainly avascular and supplied by passive
diffusion from the vertebral endplates. The L4/L5 disc space is the largest avascular
structure in the body. Therefore, all structural changes are usually irreversible as
adult discs have limited healing potential [3]. A normal nucleus pulposus is a gelati-
nous structure with high viscosity and elasticity, comprised of proteoglycans and
intermolecular water (up to 80%), which acts hydrostatically by transmitting
mechanical forces evenly to the annulus fibrosus and endplates in every direction.
Abnormal mechanical axial stress impairs nucleus biochemical turnover and com-
position. As degeneration progresses, the nucleus pulposus becomes dehydrated
and results in reduced intradiscal pressure, thus passing the mechanical load to the
annulus fibrosus which acts like a fibrous solid to resist compression directly [3].
Each annulus fibrosus comprises 15–20 collagenous laminae running obliquely
from the edge of one vertebra down to the edge of the vertebra below and merging
anteriorly and posteriorly with longitudinal ligaments. Increased stress on the annu-
lus fibrosus may lead to cracks and cavities in the fibers, subsequently progresses
with clefts and fissures [11]. Inhomogeneous mechanical stress on the annulus
fibrosus and on their insertion on the vertebral body can produce hyperplastic
changes at the edges of the vertebral body with osteophytes formation [3]. Moreover,
this loss of fibers structural integrity of the annulus fibrosus may favorite disc her-
niation and failure to maintain anatomical alignment and vertebral position, leading
to instability and/or spondylolisthesis [3].

12.2.1.2 Imaging
At imaging, normal nucleus pulposus has a hyperintense signal on T2-weighed
images (WI), which directly correlates with proteoglycan and subsequently water
concentration. Disc dehydration corresponds to progressive signal loss on T2-WI
and loss of disc height [12].
Pfirrmann et al. developed a grading system for lumbar disc degeneration accord-
ing to magnetic resonance imaging (MRI) T2-WI, discal structure, distinction
between nucleus pulposus and annulus fibrosus and disc height (Table 12.1) [13].
Other imaging signs that can be associated with disc degenerations are: the vac-
uum phenomenon (Fig. 12.2), accumulation of nitrogen within the disc, which can
be visible both on X-ray and computed tomography (CT) as the presence of gas
within the disc and represented as a signal void on both T1 and T2-WI at MRI [14,
15]; intradiscal fluid accumulation, with hyperintense signal at T2-WI, which can
be associated with endplates degeneration, mimicking early spondylodiscitis [15];
intradiscal calcification (Fig. 12.2), which frequently involves the annulus fibrosus
and is located in the lower part of the thoracic spine [16].
322 F. Serpi et al.

Table 12.1 Classification of disc degeneration at MRI

Distinction
of nucleus Height of intervertebral
Grade Structure and anulus Signal intensity disc
I Homogeneous, bright Clear Hyperintense, Normal
white isointense to
cerebrospinal fluid
II Inhomogeneous with or Clear Hyperintense, Normal
without horizontal isointense to
bands cerebrospinal fluid
III Inhomogeneous, gray Unclear Intermediate Normal to slightly
decreased
IV Inhomogeneous, gray Lost Intermediate to Normal to moderately
to black hypointense decreased
V Inhomogeneous, black Lost Hypointense Collapsed disc space

a b

Fig. 12.2 Signs of disc degeneration. The vacuum phenomenon is due to the accumulation of
nitrogen within the disc (arrows), represented as air density within the disc in CT (a). Intradiscal
calcification typically involve the annulus fibrosus, as in this picture (arrow) at the level of the
posterior fibers of the intervertebral disc L5-S1 (b)

A normal annulus fibrosus has a hypointense signal in all MR sequences.

Annulus fissures can be located within the fibers or can either involve the fibers at
their insertions on the adjacent endplates. The term “annular tear” should be dis-
couraged because it might be misunderstood as an injury [10].
A small amount of fluid interposes in the annular fissure, corresponding to
T2-weighted MRI scans of localized high intensity zones (HIZ) within the annulus
[10]. Annulus fibrosus fissures can be circumferential, radial, or peripheral [3] or
concentric, radial, or transversal, according to another classification system [10].
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 323

A circumferential or concentric fissure (Fig. 12.3) is a separation or delamination

of annular transverse fibers parallel to the peripheral contour of the disc. A radial
fissure is a vertically, horizontally, or obliquely oriented separation of annular fibers
that extends from the nucleus peripherally to or through the annulus. A peripheral
or transverse fissure is a horizontally oriented radial fissure, usually limited to the
peripheral annulus that disrupts Sharpey’s fibers (Fig. 12.4) [3, 10].
Acute fissure can be associated with pain, although the MRI appearance does not
change over time, thus it is not possible to discriminate between acute and chronic
fissures at imaging [3, 17].
An HIZ itself may represent the actual annular fissure or alternatively may rep-
resent vascularized fibrous tissue (granulation tissue repair) within the substance of
the disc in an area adjacent to a fissure, with a positive Gadolinium contrast uptake
on MRI. Therefore, visualization of an HIZ does not imply a traumatic etiology or
that the disc is a source of pain [10].

Fig. 12.3 Circumferential fissure of the posterior annular fibers at L4-L5. It consists of the separa-
tion or delamination of annular transverse fibers parallel to the peripheral contour of the disc (arrows)

Fig. 12.4 A circumferential or concentric fissure is a separation or delamination of annular trans-

verse fibers parallel to the peripheral contour of the disc. A radial fissure is a vertically, horizon-
tally, or obliquely oriented separation of annular fibers that extends from the nucleus peripherally
to or through the annulus. A peripheral or transverse fissure is a horizontally oriented radial fissure,
usually limited to the peripheral annulus that disrupts Sharpey’s fibers
324 F. Serpi et al.

12.2.1.3 Disc Displacement

Displacement of disc material beyond the normal margins of intervertebral disc
space can be either diffuse (“bulging”) or focal. According to the nomenclature of
the combined task forces of the North American Spine Society (NASS), the
American Society of Spine Radiology (ASSR), and the American Society of
Neuroradiology (ASNR), the presence of disc tissue extending beyond the edges of
the ring apophyses (exclusion of the osteophyte formation), throughout the circum-
ference of the disc, is called “bulging” and is not considered a form of herniation
[10]. On axial plane it involves more than 25% of the circumference of the disc and
typically extends a relatively short distance, usually less than 3 mm, beyond the
edges of the apophyses (Fig. 12.5). A bulging can be either symmetric or asymmet-
ric. Asymmetric bulging is defined as the presence of more than 25% of the outer
annulus beyond the perimeter of the adjacent vertebrae, more evident in one section
of the periphery of the disc than another, but not sufficiently focal to be character-
ized as a protrusion [10]. Asymmetrical bulging is often seen as an adaptation to
adjacent deformity, such as scoliosis.
Focal displacement, instead, refers to the extension of the disc material less than
25% of the periphery of the disc as viewed in the axial plane and it is called disc
herniation. The herniated material may be nucleus, cartilage, fragmented apophy-
seal bone, annular tissue, or any combination of them (Fig. 12.6) [10].
Herniated disc can be further classified according to:

• Shape of the herniated material: protruded or extruded (Fig. 12.7). Protrusion is

present when the distance between the edges of the disc herniation is less than
the distance between the edges of the base. Extrusion is present when, at least in
one plane, any distance between the edges of the disc material is greater than the

Fig. 12.5 Bulging L4-L5. A bulging refers to the presence of disc tissue extending beyond the
edges of the ring apophyses, involving more than 25% of the circumference of the disc on axial
plane and typically extending a relatively short distance
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 325

Fig. 12.6 A bulging is the presence of disc tissue extending beyond the edges of the ring apophy-
ses more than 25% of the circumference of the disc and typically extends a relatively short dis-
tance. Disc herniation refers to the extension of disc material less than 25% of the circumference
of the disc

a b

c d

Fig. 12.7 Protrusion L5-S1 (arrow), the distance between the edges of the disc herniation is less
than the distance between the edges of the base (a, b). Extrusion L5-S1 (arrow), the distance
between the edges of the disc material is greater than the distance at the base, extending in the right
subarticular space with possible conflict with the nerve root of S1 (c, d)

AL GRAWANY
326 F. Serpi et al.

a b

c d

Fig. 12.8 Contained left subarticular hernia at L5-S1. L5-S1 (arrows), without transligament
involvement (a, b). Uncontained right subarticular hernia at L5-S1 (arrows), with transligament
caudal migration (c, d)

distance at the base [10]. Extruded hernia on the sagittal plane sometimes causes
the posterior longitudinal ligament to tent, which often causes neurological
symptoms and pain [3].
• Containment: contained or uncontained (Fig. 12.8). A hernia is contained if the
displaced portion is covered by outer annulus fibers and/or the posterior longitu-
dinal ligament, or uncontained in the absence of posterior covering. Referring
specifically to the posterior longitudinal ligament, some authors have distin-
guished displaced disc material as subligamentous, extraligamentous, transliga-
mentous, or perforated. The term subligamentous is favored as an equivalent to
contained [10]. Due to limitation of CT and MRI, it is not always possible to
discriminate between contained and uncontained herniation. Nevertheless, if the
posterior margin of the herniated disc is smooth on axial plane, it is likely con-
tained, whereas if the margins are irregular, it is likely uncontained. CT discog-
raphy does not always allow to distinguish whether the herniated components of
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 327

a disc are contained, but only whether there is a communication between the disc
space and the vertebral canal [10].
• Continuity: Extruded discs in which all continuity with the disc of origin is lost
may be further characterized as “sequestrated.” A sequestrated hernia can be
either contained (subligamentous) or not. More generally, disc material displaced
away from the site of extrusion, in either sagittal or axial plane, may be character-
ized as “migrated.” Migration refers to the position of the displaced disc material,
rather than to its continuity with the disc of origin; therefore, it is not synonymous
with sequestration. A migrated disc can be sequestrated or not (Fig. 12.9) [10].
• Volume and Composition: Due to anatomical interindividual differences, there is
no universal classification to assess spinal canal involvement. A simple scheme
is to assess spinal canal compromission on axial plane. Less than one-third is
considered “mild,” from one- to two-third “moderate,” and more than two-third
“severe” [10]. Acute disc herniation has usually high water content with hyper-
intense signal on T2-WI and tends to dehydrated and shrink over time, which
leads to progressively volume decrease and loss of signal in T2-WI.

a b

Fig. 12.9 L4-L5 hernia (arrow), caudally migrated without sequestrum (a). L4-L5 hernia, crani-
ally migrated with sequestrum (arrow). The extruded material has lost the continuity with the disc
of origin (b)
328 F. Serpi et al.

• Location: Based on the position of the herniation compared to anatomical land-

marks, hernias can be classified on axial plane (Fig. 12.10) as central, right/left
subarticular, right/left foraminal, right/left extraforaminal, or anterior. On sagit-
tal plane (Fig. 12.11) they can be classified as discal, infrapedicular, pedicular, or
suprapedicular.

Principal disc displacement characteristics and classification are summarized in

Table 12.2.

Fig. 12.10 Location of

hernias classified on axial
plane
EXTRA-
FORAMINAL
OR ANTERIOR

FORAMINAL

SUBARTICULAR

CENTRAL

SUPRAPEDICULAR

PEDICULAR

INFRAPEDICULAR

DISCAL

Fig. 12.11 Location of hernias classified on sagittal plane

12 Osteoarthritis in Axial Skeleton in Geriatric Patients 329

Table 12.2 Summary of principal disc displacement characteristics and classification

Disc displacement
Bulging Symmetric/ Asymmetric bulging: more evident in one section of the periphery
(>25%) asymmetric of the disc than another
Hernia Protrusion/ Protrusion, when the distance between the edges of the disc
(<25%) extrusion herniation is less than the distance between the edges of the base.
Extrusion, when, at least in one plane, any distance between the
edges of the disc material is greater than the distance at the base
Contained/ Contained, if the displaced portion is covered by outer annulus
uncontained fibers and/or the posterior longitudinal ligament
Uncontained, absence of posterior covering
Sequestrated/ Sequestrated, extruded hernia in which all continuity with the disc
migrated of origin is lost
Migrated disc material displaced away from the site of extrusion,
independently from continuity
Volume Based on spinal canal compromission on axial plane: mild (<1/3),
moderate (1/3–2/3), severe (>2/3)
Composition Acute disc herniation: high water content, hyperintense signal on
T2 WI MRI
Chronic disc herniation: dehydrated, progressively volume
decreased, and loss of signal in T2 WI MRI
Location Axial plane: central, right left subarticular, right/left foraminal,
right/left extraforaminal or anterior
Sagittal plane: discal, infrapedicular, pedicular, or suprapedicular

12.2.1.4 Symptoms and Complications

• Neurological complications: Pain is usually associated with posterior/foraminal
spinal cord or neural compression. Annular fissure and acute disc herniation
involving the anterior aspect of the disc can also be responsible for back pain.
According to pathogenesis, nerve compression is not only related to disc hernia-
tion, but it can also be caused by other etiologies, such as hypertrophic joint facet
osteoarthritis or facet cysts. Indirect signs for nerve root compression are enlarge-
ment of the nerve root (pre- and post-compression) and nerve root enhancement
after intravenous Gadolinium administration. The underlying mechanism for
nerve enlargement and enhancement may relate to inflammation and alteration of
the blood/nerve barrier [18]. In the lumbar spine, nerve roots in the intervertebral
foramen are located superior to the intervertebral discs. Therefore, a foraminal
herniation does not necessarily affect the nerve root. Symptoms caused by neural
compression at the lumbar level has often a multifactorial etiology (disc hernia-
tion, dorsal spondylophytes, flavum ligament hypertrophy, and osteoarthritis of
the facet joint). Complete absence of fat around the nerve root in the interverte-
bral foramen is consistent with nerve root compression in the lumbar spine [19].
In contrast, in the cervical spine the nerve roots at the intervertebral foramen are
located at the same level or slightly below the interverbal discs. Therefore, a
small protrusion might already cause symptoms. Fat visibility around the nerve
root in the intervertebral foramen is an unreliable sign in the cervical spine [19].
There is no universally accepted radiological definition to distinguish between
acute, subacute, and chronic disc herniations. From a neurological point of view,
330 F. Serpi et al.

patients with symptoms and pain can be divided into acute (up to 4 weeks), sub-
acute (between 4 and 12 weeks), and chronic (more than 12 weeks) [20].
• Vascular complications: They develop secondary to acute or chronic com-
pression of the vertebral artery or medullary segmental arteries feeding the
spinal cord (large cervical radiculomedullary at C5–C7; dominant radiculo-
medullary artery at T4–T5; the artery of Adamkiewicz located at T10 and the
additional radiculomedullary artery of Desproges-Gotteron arises at L4–L5),
which may cause a severe neurological deficit and also may require interven-
tion [3].
• Focal complications: They can occur because of chronic persistent inflamma-
tion, such as epidural scarring, which may limit nerve roots passage through
foramina and may cause nerve root tethering. This process is virtually impossi-
ble to identify at imaging [3]. Intradural herniation (very rare) and epidural vein
varicosis are other possible focal complications [3].

12.2.2 Endplate Changes

Endplates play a crucial role to maintain the mechanical environment as well as

the proper nutrition of avascular discs. With aging, spinal bodies endplates
undergo changes which comprehend thinning of the endplates, focal endplate
defect, and somatomarginal osteophytes, all without alteration of signal of sub-
chondral bone marrow on MRI. On the contrary, abnormal load and stress affect
vertebral endplates bone marrow, leading to histological degenerative changes.
According to the Modic classification (Fig. 12.12), type I change corresponds to
bone marrow edema and vascularized fibrous tissues (decreased signal intensity
on T1-WI, increased signal intensity on T2-WI, and enhancement after contrast
administration), type II reflects the presence of yellow marrow (increased on
T1-WI, iso/hyperintense on T2-WI without contrast enhancement), and type III
represents sclerotic reaction (decreased on both T1- and T2-WI). Type I is strongly
associated with unspecific lumbar pain and can slowly progress to type II; how-
ever, reverse reconversion has also been reported [21]. Type I is related either to
biomechanical or biochemical factor. In fact, the uneven distribution of loads due
to disc degeneration creates fissures and microfractures of the endplates. Moreover,
the intravertebral migration of the nucleus pulposus with high concentration of
inflammatory substances results in local bone marrow inflammatory reaction [3].
Type III is stable and almost always asymptomatic [22]. Modic type I may some-
times mimic a vertebral infection. Diffusion weighted imaging (DWI) is useful for
differentiating degenerative and infectious endplates bone marrow abnormalities.
Modic I shows the so-called claw sign on DWI, which is a linear, well-margin-
ated, typically paired region of restricted diffusion, situated within the adjoining
vertebral bodies, at boundaries between normal marrow and vascularized end-
plates marrow. Typically, a slow progressive degenerative disease produces a
well-defined border response. Conversely, an infection process can develop very
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 331

Fig. 12.12 Modic classification of endplates degenerative changes. Modic I: bone marrow edema
and vascularized fibrous tissue; Modic II: yellow marrow metaplasia; Modic III: sclerotic reaction

quickly, with diffuse infiltrate of pathogens and edema of the marrow, without a
well-defined border and a claw sign [3, 23, 24].

12.2.3 Facet Joints

Facet joints are true synovial joints, presented at every intervertebral level, except at
C1-C2. They contribute to spinal movement and, as any other synovial articulation,
they can be subjected to degenerative disease. Although facet joint osteoarthritis
may occur independently and could be a source of pain on its own, it typically rep-
resents a secondary process that is associated with disc degeneration and loss of disc
height [3]. The consequently altered motion and increased stress on the facet joint
result in arthrosis, osteophytes, synovial cysts, and craniocaudal subluxation
(Fig. 12.13) [3]. Moreover, with aging, paraspinal muscles mass decreases, which
contributes to facet joint osteoarthrosis by allowing poorly controlled segmental
motion [25]. Joint osteoarthrosis can be classified based on osteophytes formation
and joint space narrowing [3, 26].
Degenerative synovial changes can also produce synovial cysts (Fig. 12.14),
with the majority located at the lumbar (L4-L5) level. They are usually hyperintense
on T2-WI but can also be hyperintense at T1-WI if they contain hemorrhagic or
proteinaceous components [3]. Clinically speaking, hypertrophic facet joint osteo-
arthritis can determine stenosis of the canal and of the preforaminal or foraminal
space, leading to symptoms related also to neural elements compression. Moreover,
facet joint osteoarthritis plays an important role in spinal instability and anterior
332 F. Serpi et al.

Fig. 12.13 Facet joint

osteoarthritis. Severe
narrowing and almost total
loss of joint space,
sclerosis and osteophyte
formation

degenerative spondylolisthesis (Fig. 12.15). The different orientation of joint facets

influences facet joints subluxation, which is more common at L4-L5, due to sagittal
orientation of facet joints, rather than L5-S1, where facet joints have a coronal-­
oblique orientation, thus preventing forward displacement [27].

12.2.4 Ligamentum Flavum

Ligamentum flavum is also called yellow ligament, due to the high content of yel-
low elastin. It is composed of two adjacent laminae, extending from the second
cervical vertebra to the first sacral vertebra, forming the posterior boundary of the
spinal canal [3]. Degenerative disc alterations and herniation, together with facet
joint osteoarthritis, determine abnormal movements and instability, which is a
potential trigger for ligamentum flavum thickening (Fig. 12.16). The term “hyper-
trophy” should be discouraged because the degenerative process is not character-
ized by an enlargement of cellular elements, but by a degeneration of elastic fibers
and an accumulation of collagen due to chronic inflammation; this process deter-
mines corrugation of the ligament and predisposes to calcification (Fig. 12.17) [28].
However, this can contribute to reduction of the diameter of the spinal canal and
represents one of the elements that can participate in the spinal canal stenosis [3].
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 333

a b

c d

Fig. 12.14 Left facet joint fluid accumulation at L4-L5, arrows (a, b), with initial formation of a
synovial cyst. In the axial plane, facet fluid is also accumulated on the right side (b) but in less
quantity. Left facet joint synovial cyst at L4-L5 (c, d), extending in the spinal canal (arrows)

12.2.5 Interspinous Processes

Degenerative changes of the interspinous processes, also known as Baastrup disease

or “kissing spine,” are less common than facet joint osteoarthrosis and predomi-
nately located in the lumbar spine. They are characterized by interspinous space
reduction, with marginal sclerosis, osteophytes, bony erosions, and the presence of
a neosynovial joint or interspinous bursitis, visible on MRI as a concave up liquid
signal between consecutive spinous processes (Figs. 12.18 and 12.19) [29].
Clinically, it is associated with lower back pain that increases with extension or after
pressing the spinous processes and that is relieved in flexion [29].
334 F. Serpi et al.

Fig. 12.15 L4-L5 anterior degenerative spondylolisthesis (star) with facet joints sublux-
ation (arrow)

Fig. 12.16 Ligamentum flavum thickening (arrows). This contributes to the reduction of spinal
canal size
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 335

Fig. 12.17 Chronic

inflammation predisposes
to ligamentum flavum
calcification (arrow)

Fig. 12.18 Degenerative changes of the interspinous processes: interspinous bursitis. L3-L4
small fluid collection both on STIR sequence of the left and T2 weighted sequence on the right
(arrows)

AL GRAWANY
336 F. Serpi et al.

Fig. 12.19 Degenerative

changes of the interspinous
processes: space reduction
with bone erosion and
bone edema the opposed
spinous processes, also
known as “kissing spine”
(arrows)

12.2.6 Instability, Spondylolisthesis, Spinal Canal, and Nerve

Foramina Stenosis

Due to degenerative changes of the disc, facet joints, and ligamentous apparatus, the
ability to maintain the anatomical alignment of the functional spinal unit, at static
position and/or during movements, decreases. This results in functional instability
and degenerative spondylolisthesis. It typically occurs at lumbar or cervical levels
and is virtually absent in the thoracic spine, thanks to costovertebral joints which act
as a further stabilizer.
Instability can be defined as an abnormal response to applied loads characterized
kinematically by abnormal movement beyond normal constraints [30].
Spondylolisthesis refers to forward slippage of a vertebra on the subjacent one in
the sagittal plane. Backward vertebral slippage, a type of spondylolisthesis, has
been called retrolisthesis [14].
The process of degenerative instability is divided into three phases: early dys-
function, instability, and stabilization [31]. The first phase (early dysfunction) is
characterized by initial and reversible anatomical modifications induced by altered
axial load. In the second phase (instability), anatomical changes progress with disc
height reduction, capsule-ligament laxity, and facet joint osteoarthrosis. Finally, in
the third phase (stabilization), new biomechanical constraints occur induced by ana-
tomical changes, such as osteophytes and intervertebral space reduction, which lead
to a new spinal mechanical stabilization, however at the cost of movement reduction
[32]. In the third stage sometimes spondylolisthesis has already occurred. In fact,
the radiologic observation of degenerative spondylolisthesis does not necessarily
imply intervertebral instability at the time of imaging because a new stabilization
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 337

may have already occurred [14]. Degenerative instability consists of pure motion
dysfunctional syndrome with no or minimal anatomical changes, undetectable on
imaging (microinstability), or overt instability, which can be radiologically detect-
able [33]. As persistent uni- or multisegmental instability progresses, it leads to
rotational and translational vertebral subluxation, resulting in degenerative spondy-
lolisthesis, which may be stable or unstable [3].
Conventional MRI and CT performed in the prone position provides limited
information on the functional status of the affected segment as spondylolisthesis
with instability may “self-reduce” without a normal axial load [3]. Therefore, diag-
nosis is based both on direct and indirect signs of instability, such as joint facets

INDIRECT SIGNS OF INSTABILITY

FACET SYNOVIAL INTERSPINOUS FACET JOINT VACUUM

FLUID CYSTC FLUID HYPERTROPHY PHENOMENOM

Fig. 12.20 Major indirect signs of instability

Fig. 12.21 Meyerding classification of spine spondylolisthesis

338 F. Serpi et al.

Fig. 12.22 Grade III of

spondylolisthesis
according to Meyerding
classification

fluid, facet synovial cysts, interspinous fluid, facet joints hypertrophy, and intradis-
cal vacuum phenomenon (Fig. 12.20) [3].
Functional flexion/extension radiographs are considered the gold standard for
diagnosing the presence of degenerative instability in the setting of spondylolisthe-
sis [34]. For lumbar spine spondylolisthesis, the Meyerding classification is a com-
mon method for grading anterior vertebral spondylolisthesis, based on the ratio of
the overhanging part of the superior vertebral body to the anteroposterior length of
the adjacent inferior vertebral body (Figs. 12.21 and 12.22).
For the lumbar spine, on flexion-extension radiographs, values of 10° for sagittal
rotation and 4 mm for sagittal translation are typically used to infer instability [14].
For the cervical spine, a slippage of 3 mm on functional radiographs is considered a
reliable cut-off [3].
Degenerative spondylolisthesis is an important factor that can contribute to spi-
nal canal stenosis, which is defined as a decrease in the area that can affect the spinal
canal, the lateral recesses, or neural foramina, compressing neural and vascular
structure, thus resulting in various degrees of clinical disabilities [3, 16].
Degenerative spinal canal stenosis is considered a multifactorial condition, rather
than an answer to a single insult. In fact, there are four major factors that can con-
tribute to spinal canal stenosis that should be always checked carefully: disc hernia-
tion, hypertrophic facet joint osteoarthrosis, ligamentum flavum hypertrophy, and
spondylolisthesis (Fig. 12.23) [3].
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 339

Fig. 12.23 Major factors that contribute to spinal canal stenosis, which is usually the result of a
multifactorial condition

Grading systems based on spinal canal measurements appear impractical; there-

fore, qualitative assessment of the relationships between the anatomical structures
plays a major role in establishing the presence of spinal canal stenosis [3].
According to the combined task forces of the North American Spine Society
(NASS), the American Society of Spine Radiology (ASSR), and the American
Society of Neuroradiology (ASNR), canal compromise less than one-third is con-
sidered “mild” between one-third and two-third “moderate,” and more than two-­
third “severe.” The same grading can be applied to neuroforaminal involvement [10].
Other lumbar spine stenosis classification systems, based on MR imaging, are
Lee and Schizas classification. The Lee system is a 4-grade classification system
based on the obliteration of cerebrospinal fluid (CSF) space in front of the cauda
equina in the dural sac and the separation degree of the cauda equina on T2-W axial
MRI. Grade 0, no lumbar central canal stenosis (LCCS), refers to no obliteration of
the anterior cerebrospinal fluid (CSF) space. Grade 1, mild LCCS, refers to mild
obliteration of the anterior CSF space but all elements of the cauda equina clearly
separated from each other. Grade 2, moderate LCCS, refers to moderate obliteration
of the anterior CSF space and some cauda equina aggregation where it is impossible
to identify each other visually. Grade 3, severe LCCS, refers to severe obliteration
of the anterior CSF space, marked compression of the dural sac and the entire cauda
equina appearing as one bundle [35].
The Schizas system is a 7-grade classification system based on the morphology
of the dural sac on T2-W axial MRI with the rootlet/CSF fluid ratio taken into
account. Grade A, no or minor stenosis, refers to clearly visible CSF inside the dural
sac within homogeneous distribution. Grade A1 refers to the condition where the
rootlets lie dorsally and occupy less than half of the dural sac area. Grade A2 refers
to cases where the rootlets lie dorsally, in contact with the dura but in a horseshoe
configuration. Grade A3 refers to rootlets lying dorsally and occupying more than
half of the dural sac area. Grade A4 refers to cases where the rootlets lie centrally
340 F. Serpi et al.

Fig. 12.24 Grade C

stenosis (Schizas
classification)

Fig. 12.25 Grade D

stenosis (Schizas
classification)

and occupy the majority of the dural sac area. Grade B, moderate stenosis, includes
cases where the rootlets occupy the entire dural sac, but can still be individualized.
Grade C (Fig. 12.24), severe stenosis, refers to cases where no rootlets can be rec-
ognized, with the dural sac demonstrating a homogeneous gray signal with no vis-
ible CSF signal, but epidural fat present posteriorly. Grade D (Fig. 12.25), extreme
stenosis, refers to no rootlets being recognizable and no epidural fat posteriorly [36].
12 Osteoarthritis in Axial Skeleton in Geriatric Patients 341

12.3 A Focus on Imaging Techniques and Their Role

in the Assessment of the Degenerative Spine

Conventional radiography usually represents the first level examination for the
spine, allowing a good assessment of spinal alignment, vertebral bodies morpholo-
gies, calcifications, and the vacuum phenomenon. However, it has a marginal role
due to technical limitations, mostly due to air and other structures overlap and the
impossibility to study bone marrow, neural structures, and soft tissue. The standard
projections are the anteroposterior and latero-lateral view. In addition, the oblique
view is used for the assessment of foramens and, eventually, spondylolysis (scotty
dog sign) [32]. Moreover, functional flexion/extension radiographs are considered
the gold standard for diagnosing the presence of degenerative instability in the set-
ting of spondylolisthesis [34].

Computed tomography has a better accuracy in the assessment of bone margins

and osteophytes, and it represents the reference standard for spondylolysis. Thanks
to its high resolution for small bone alteration of the posterior arch, it is useful for
the evaluation of the spinal canal and neural foramina [32]. However, like tradi-
tional radiography, it has a limited role in the assessment of soft tissue and neural
structures.

MRI is the first-choice technique for the study of discs and ligaments changes.
MRI of the spine is generally performed with the patient in supine position. Upright
MRI is also feasible and favored by some groups due to the plausible explanation
that axial loads on the intervertebral disc are reduced in supine position. However,
upright MRI is limited by poor resolution, very limited availability, increased
motion artifacts, and high false-positive findings [37, 38].

The standard MRI protocol typically includes two-dimensional (2D) sagittal

T1-W fast spin-echo (FSE), sagittal T2-W FSE, and axial T2-W FSE images. Most
institutions add a short tau inversion recovery (STIR) sequence, a gradient echo
sequence (particularly in the cervical spine), and coronal proton density weighted
(PDw), T2-W or T1-W sequence. High-resolution three-dimensional (3D) sequences
with secondary reconstruction are particularly helpful in the cervical spine. In fact,
secondary reformatted images can be better oriented along the oblique sagittal plane
to show the foramen and higher resolution allows better assessment of the relatively
small cervical nerve roots. The sagittal images are used to evaluate the vertebral
bodies, intervertebral discs, ligaments, facet joints, spinal canal, spinal cord and/or
sac and intervertebral foramen. The STIR images are usually performed in the sagit-
tal plane and are useful to identify bone marrow edema. Axial images are useful for
confirmation and evaluation of central canal stenosis, cord signal change, disc her-
niations, spinal cord compression, and nerve root compression. The facet joints are
best assessed on axial images for the presence of arthrosis, synovitis, and indirectly
for segmental instability. The coronal images, if performed, are particularly helpful
342 F. Serpi et al.

for identification and classification of lumbosacral transitional vertebra, for an over-

view of the extent of scoliosis and for detection of extraforaminal herniations.
Gradient echo sequences may be used to evaluate calcification and ossification of
the ligaments and to identify posterior endplate ridges, particularly in the cervical
spine. The use of contrast can be helpful in the postoperative setting. Contrast
administration is useful to discriminate between disc material and fibrosis. There is
a diffuse contrast-media uptake in epidural fibrosis/granulation tissue, while there is
only rim-enhancement in disc tissue. Further, partially healed chronic annular tears
may demonstrate enhancement due to the presence of granulation tissue, not identi-
fied in normal T2-W non-contrast MR images. MR neurography including diffusion
tensor imaging (DTI) techniques for the spinal cord and nerve roots are currently
only used for specific questions (e.g., in patients with neurofibromatosis) and for
research purpose, but not yet used in standard protocols. Novel functional imaging
techniques, such as T2/T2* mapping, T1ρ calculation, T2 relaxation time measure-
ment, diffusion quantitative imaging, chemical exchange saturation transfer, delayed
contrast-enhanced MRI of cartilage, sodium-MRI and MR spectroscopy, are prom-
ising tools that may allow the evaluation of early disc degeneration [3, 19].
However, independently from the imaging technique, it is important to keep in
mind that the presence of degenerative change is not itself an indicator of symp-
toms. In fact, altered radiological findings do not always have corresponding clini-
cal symptoms and pain and, conversely, clinical pain does not always correlate to
the presence and severity of radiological changes. Therefore, determination of the
relationship between imaging anatomical changes and its symptoms remains chal-
lenging. Moreover, some anatomical changes encompass the normal spectrum of
aging and are not associated with degenerative pathology. Further, the majority of
standard examinations are usually performed in supine position, in the absence of
axial load, and in static conditions, possibly increasing the number of false nega-
tive exams.
When patients with degenerative spine diseases are referred for imaging, the
important task is to identify the main cause of the patient’s pain or neurological
symptoms, keeping in mind that degenerative pathology is a biomechanical con-
tinuum of anatomical alterations and that a degenerative finding should not be con-
sidered an isolated event or reported as a random finding. This interpretation,
associated with the detection of direct and indirect signs of instability, is useful to
guide the referring physician to choose a targeted treatment option [3].

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Osteoarthritis in Appendicular Skeleton
in Geriatric Patients 13
Antonio Barile, Riccardo Monti, Federico Bruno,
Julia Daffinà, Francesco Arrigoni, and Carlo Masciocchi

13.1 Introduction

Osteoarthritis (OA) is the most common form of arthritis and is the third leading
cause of disease burden in developed countries with significant social and health
impact. As the average age and life expectancy are increasing, this form of arthritis
is expected to increase in the incoming decades. OA commonly affects weight-­
bearing joints such as the knee, which is most commonly affected, and the main
clinical features are pain and stiffness. The gravity of this disease leads to a progres-
sive decline in physical functioning. Imaging plays a vital role in initial diagnosis,
staging, and monitoring of longitudinal progression and provides indications for
conservative, minimally invasive, or surgical treatment. Although the primary focus
of imaging lies in bone alterations, osteoarthritis should be framed as a whole organ
disease, and multimodal instrumental evaluation is essential to highlight the various
joint components involved and their alterations.

13.2 Shoulder Osteoarthritis

Compared to other appendicular joints, the glenohumeral joint is one of the least
commonly affected by osteoarthritis. The estimated radiographic prevalence is in
the range of 16–20% in an elderly population. The main risk factor for glenohu-
meral osteoarthritis is age. Other factors that increase the likelihood risk of devel-
oping shoulder osteoarthritis include female gender, obesity, Caucasians, previous
trauma, rotator cuff tears, glenohumeral instability, and crystalline arthropathy. In

A. Barile (*) · R. Monti · F. Bruno · J. Daffinà · F. Arrigoni · C. Masciocchi

Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila,
L’Aquila, Italy
e-mail: [email protected]; [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 345
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_13

AL GRAWANY
346 A. Barile et al.

addition to idiopathic origin, further causes of glenohumeral osteoarthritis are the

presence of prior trauma, glenohumeral dislocation, proximal humeral fractures,
shoulder osteonecrosis, inflammatory arthritis, septic arthritis, hemochromatosis,
hemophilia, and iatrogenic causes such as multiple injections of intra-articular
steroids [1].
Symptoms are usually slowly progressive, characterized by posterior or deep
localized shoulder pain associated with limited range of motion and stiffness. Other
symptoms include blockage, grinding, and joint instability. As in other diarthrodial
joints, glenohumeral osteoarthritis is associated with the thickening of the subchon-
dral bone plate and the formation of marginal osteophytes, which can usually be
seen both on the posterior glenoid rim and on the central part of the humeral head.
The soft tissue changes associated with this condition are the capsular thickening
and contraction, potentially leading to a deficit of internal rotation, and the further
eccentric erosion of the posterior glenoid [2].
As with other joint OA involvements, general imaging hallmarks comprehend
osteophyte formation, joint space narrowing, and subchondral bone plate sclerosis,
whereas subchondral cyst formation and joint surface remodeling or deformity are
seen in later stages.

13.2.1 Conventional Radiography (CR)

To assess the presence and degree of arthritis in the glenohumeral joint the first step
is conventional radiography. Standard projections include an anteroposterior view,
a Grashey view (AP oblique internal rotation), and a further axillary view. These
views allow grant the assessment of the presence, type, and degree of arthritis and
rule out other conditions, including fractures, dislocations, and bone injuries [3].
To determine the extent of osteoarthritis of the glenohumeral joint various radio-
graphic classifications were established. The most widely adopted is the Samilson-­
Prieto classification. This classification acknowledges grade 0 is normal, grade 1 is
mild with osteophytes smaller than 3 mm on the humeral head, grade 2 is moderate
with osteophytes between 3 and 7 mm on the humeral head or glenoid rim, and
grade 3 is severe with osteophytes over 7 mm, with or without contextual joint
incongruity. The state of the rotator cuff can be inferred from the radiographic eval-
uation of Grashey’s view. This view is accessed from a lateral oblique projection at
30°, tangential to the glenohumeral joint, to obtain an image parallel to the glenoid
face in order to reveal any degenerative modifications [4].
For the rotator cuff the radiographic classification used integrity is the Hamada–
Fukuda classification, a radiographic morphological description of the natural
course of massive rotator cuff tear assessing the height of the acromiohumeral
space. There are five distinctions within this classification:

• Type 1: Normal joint morphology and acromiohumeral distance bigger than 6 mm

• Type 2: Acromiohumeral distance smaller than 5 mm
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 347

• Type 3: Type 2 plus the acetabularization (i.e., exaggerated undersurface concav-

ity) of the acromion
• Type 4: Types 2 and 3 plus the narrowing of the glenohumeral joint space
• Type 5: Types 2, 3, and 4 plus the humeral head collapse

Finally, an axillary view is essential in preoperative planning. It allows the

assessment of the posterior glenoid wear and deficiency, which has ramifications on
the glenoid preparation (concentric reaming) necessary to center the glenoid-based
implant [5].

13.2.2 Computed Tomography (CT)

For an effective preoperative planning and to assess the humeral and glenoid bone
condition, computed tomography (CT) provides greater bony detail compared to
radiographs. If there are concerns regarding the glenoid’s bone loss, the presence of
cyst, or retroversion on standard radiographs, CT should be suggested as it may
influence both the type of arthroplasty choice and the location of the glenoid com-
ponent. The CT study of the affected shoulder is necessary to estimate the glenoid
bone loss, which may require preoperative planning before eccentric reaming, aug-
mentation of bone graft, use of augmented glenoid components, or consideration of
total reverse shoulder arthroplasty. Therefore, CT evaluation should be considered
mandatory in all patients undergoing an arthroplasty procedure that requires glenoid
resurfacing (e.g., total shoulder arthroplasty and total reverse shoulder arthroplasty)
as it allows the quantification of the glenoid border and recognition of different
forms of glenoid bone loss such as cyst that can alter implant fixation and place-
ment [6].

13.2.3 Magnetic Resonance Imaging (MRI)

Besides visualizing the glenoid and humeral head morphology, MRI can help detect
the underlying etiology. Thanks to MRI, the evaluation of various tissue abnormali-
ties, regarding cartilage, labrum, and glenohumeral ligaments can be assessed.
However, the capacity of detecting cartilage lesions is limited by the comparison
with to other joints. Additionally, magnetic imaging provides valuable information
for the rotator cuff evaluation, which forms an integral part of surgical planning.
Shoulder MRI is suggested in patients with rotator cuff deficiency doubts on clinical
examination. Indeed, an intact rotator cuff is required for both hemiarthroplasty and
total shoulder arthroplasty. Therefore, the integrity of the rotator cuff is a crucial
factor in determining whether the patient is a candidate for total anatomical shoul-
der arthroplasty, hemiarthroplasty, or conversely to total reverse shoulder arthro-
plasty [7, 8]. MRI shows soft tissues with an excellent detail, it can also add
information on rotator cuff tears and on the presence and degree of muscle atrophy.
348 A. Barile et al.

The Goutallier Grading Scale of Fat Infiltration of Rotator Cuff Muscles was ini-
tially described using CT to assess the degree of fat infiltration of individual rotator
cuff muscles. Goutallier’s classification consists of: grade 0 is normal muscle, grade
1 is some fat streaks, grade 2 is less than 50% fat muscle atrophy, grade 3 is 50% fat
muscle atrophy, and grade 4 is greater than 50% of fat muscle atrophy. The impor-
tance of this classification scale is its implication in the reparability of the rotator
cuff: a degree of Goutallier fat infiltration of 3 or greater (i.e., fat infiltration equal
to or greater than 50% of muscle mass) has a 50–70% tear rate [9].

13.3 Acromioclavicular Osteoarthritis

Although AC osteoarthritis is less common than other locations such as the knee or
the hip, it is differently much more frequent than glenohumeral osteoarthritis.
Around 54–57% of elderly patients have an X-ray evidence of degenerative changes
in the AC joint. On the other hand, clinically relevant AC osteoarthritis is uncom-
mon, although it is more frequently related to other pathologies, such as the CR
upper impingement syndrome [10]. Primary osteoarthritis is strongly age-related, as
a matter of fact the degenerative process begins in early adulthood. Secondary
osteoarthritis, mainly following trauma such as joint sprains or distal clavicular
fractures, appears to be even more prevailing than primary osteoarthritis. The clini-
cal picture is pain in the anterior/superior aspect of the shoulder, sometimes radiat-
ing to the base of the neck/trapezius muscle. Daily movements or activities that
involve overhead or transverse movements increment pain. Local tenderness can be
caused by AC joint palpation. This range of symptoms is not specific and is also
reported in cervical spine disease and CR impingement syndromes, which, as afore-
mentioned, are predominant causes of shoulder pain. The direct intra-articular
injection of anesthetics can grant a differential diagnosis. The imaging evaluation of
the AC joint begins with an X-ray. This joint can be studied with average AP views
of the shoulder. However, the best option according to literature is the Zanca view
(a cephalad inclination of 10–15° with a 50% reduction in exposure compared to
standard AP view shoulder). Imaging findings are typical of degenerative diseases:
sclerosis, osteophytes, subchondral cysts, and joint space narrowing [11]. Bone
modifications seen on X-rays are evidenced more precisely on CT scan. At the same
time, MRI is more useful for evaluating changes in capsuloligamentous structures,
bone edema, and abnormalities in surrounding soft tissues (e.g., effusion of bursal
or tendon pathology) [12]. The AC joint can only be partially evaluated with
US. Still, it should be a part of routine shoulder examination, as AC joint osteoar-
thritis can sometimes mimic rotator cuff tendinopathy and may cause anterosupe-
rior impingement. AC osteophytes are found in 50% of patients with rotator cuff
tears but also in 14% of patients without rotator cuff tears. By placing the high-­
frequency linear probe on a coronal plane at the level of the joint, the evaluation of
the two articular ends of the acromion and clavicle is possible. The superior AC
ligament is clearly seen as a banded arch echo structure that overstays the bones;
below it, the joint space can vary in size and echogenicity with movements. In case
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 349

Fig. 13.1 US scan of the

acromioclavicular joint
showing capsular
distension with effusion
(arrowheads). A: acromion;
C: clavicle

of AC joint osteoarthritis, US can help evaluate superficial bone irregularities and

osteophytes, capsular hypertrophy, joint space narrowing, and joint effusion or
synovial hypertrophy (Fig. 13.1). Bilateral evaluation of the AC joint is always sug-
gested to evaluate capsular hypertrophy and joint space narrowing with increased
sensitivity. US AC joint findings should always be correlated with rotator cuff and
bursa findings and clinical picture. AC joint arthrosis-related shoulder pain can only
be diagnosed in the absence of RC abnormalities and with radiological proof show-
ing this condition. Besides, US signs of acromioclavicular osteoarthritis and rotator
cuff or bursal pathology are frequently connected; in this case, the joint injection
test can be a valuable diagnostic tool. Another frequent finding in US is an AC joint
cyst whose pathogenesis is still debated. They are however more commonly related
to full-thickness RC tears. Tendon tears cause the cranial migration of the humeral
head and damage the inferior AC joint capsule, creating a connection between the
glenohumeral joint and the AC joint [13].

13.4 Hand Osteoarthritis

Despite the high prevalence, hand OA generally receives less attention compared to
OA of the weight-bearing joints. It typically affects the distal interphalangeal (DIP)
joints and the thumb base and, less frequently, the proximal interphalangeal (PIP)
joints. Patients with hand OA can experience considerable pain, stiffness, and dis-
ability with a high impact on health-related quality of life. Outcome measures in OA
usually include evaluation of pain and disability and structural changes in the joint
can be studied with outcome [14].

13.4.1 Conventional Radiography (CR)

Currently the cheapest, most feasible, and available imaging modality for morpho-
logical assessment of the structural features of the OA hand is conventional
350 A. Barile et al.

Fig. 13.2 AP and oblique radiographic view showing initial osteoarthritis changes at the level of
the DIP with joint space narrowing and sclerosis (arrow). More advanced OA changes of the tra-
peziometacarpal joint (circle)

radiography (CR). At present, there is no established gold standard for the definition
of radiographic hand OA. Studies also differ in classification systems most com-
monly used and in the radiographic definitions of radiographic.
CR provides a two-dimensional picture of bone modifications, such as osteo-
phytes, erosions, cysts, and sclerosis and joint space narrowing (JSN) as an indirect
measure of cartilage loss (Fig. 13.2). Osteophytes can be divided into “true” intra-­
articular osteophytes and traction spurs. “True” intra-articular osteophytes are found
at joint margins and can be easily seen on CR with a traditional posteroanterior
view. Traction spurs are differently located at the extensor tendon insertion or on the
central shaft and are most easily seen on CR with an oblique or lateral view. Whether
these enthesophytic changes are related to OA is not entirely clear, previous studies
have suggested that they are mainly related to age and local biomechanical factors
and not to systemic enthesopathy [15].
Since cartilage is indirectly evaluated by the inter-osseous distance, the radio-
graphic measurement of JSN is currently recommended as an imaging endpoint for
clinical trials of disease-modifying OA drugs. The radiological assessment may be
affected by the hand positioning (e.g., flexion deformity) and is further complicated
by erosive development in the fingers joints, which can lead to increased joint space
width (JSW) (pseudo-enlargement) despite the worsening of the disease.
Radiographic erosions in hands with OA are seen as bone damage in the central part
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 351

of the joints with a typical gull-wing configuration. These erosions typically occur
in the DIP and PIP joints, but they have been described in the joints of the base of
the thumb as well. Longitudinal studies have shown that JSN precedes erosive
development, suggesting that local biomechanical factors are important for erosive
development. These findings may suggest that erosive hand OA represents severe
hand OA rather than a different disease entity. Whereas cysts are identified by the
loss of trabecular structure, sclerosis gives an increased density in the CR. Both
features can be related to bone remodeling [16].
At present, there is no consensus on the preferred grading scale. The first pro-
posed radiographic scoring system was the Kellgren and Lawrence (K&L) scale
which is the most widely used so far. The K&L scale classifies OA over a range
from 0 to 4 points (where grade of at least 2 is OA) based on different factors. These
include: the presence/severity of osteophytes, JSN, sclerosis, pseudocystic areas,
and altered shape of the bony ends. In spite of different grading descriptions for
various joint groups and difference between publications, there is general confusion
in the way of interpreting the various grades. Furthermore the K&L scale is criti-
cized for the emphasis given to osteophytes; however, sclerotic joints cannot be
classified as OA unless osteophytes are present. Therefore, several studies used
modified K&L scales to overcome these limitations. The evaluation of individual
characteristics instead of using a global score can optimize the joint assessment,
hence the OARSI (Osteoarthritis Research Society International) atlas is more fre-
quently used. With this atlas as a reference, the presence and severity of individual
characteristics (osteophyte, JSN, malalignment, erosion, subchondral sclerosis,
subchondral cysts) are assessed on semi-quantitative scales at the level of DIP, PIP,
first CMC, thumb and trapezionavicular joint. However, scoring individual features
can take longer [17].
Standard radiographs to characterize the basal thumb joint include PA, lateral
and oblique views of the hand or wrist. Arthritis of the basal joint of the thumb is
most commonly described using the Eaton-Littler classification which was first pro-
posed in 1973 and modified in 1987 by Eaton and Glickel. In this classification,
stage I is given by normal joint contours with mild joint widening (secondary to
synovitis, ligamentous laxity, or effusion), while stage II shows mild joint space
narrowing (<2 mm), mild sclerosis, subchondral cysts, and/or periarticular debris.
Stage III follows with noticeable joint space narrowing, prominent sclerosis, sub-
chondral cysts, and periarticular debris. Finally, stage IV concerns the scapho-­
trapezius joint, plus the narrowing’s worsening, increased sclerosis, and the presence
of subchondral cysts. In the clinical examination, CMC subluxation, metacarpal
adduction, and MCP hyperextension are seen. However, the Eaton-Littler classifica-
tion has its flaws, including only moderate compatibility with clinical presentations,
morphological findings and therapeutic recommendations, and sub-optimal inter-
and intra-observer variability. Although some authors underline the convenience of
transverse imaging (e.g., MRI, ultrasound, CT) in basal thumb joint arthritis diag-
nosing, there is currently no recommended role for advanced imaging [18].
352 A. Barile et al.

13.4.2 Ultrasonography (US)

In recent years, ultrasonography has been acknowledged as a useful tool for finger
joints’ inflammation evaluation in patients with rheumatoid arthritis. Recently, the
prevalence, validity, and reliability of US characteristics have also been studied in
patients with hand OA. By scanning the joint in both longitudinal and transverse
projection we can obtain conditions regarding the dorsal appearance with the joint
in full flexion, while volar aspects are studied with the joints in a neutral position.
US allows visualization of a broad spectrum of OA features of the hand, including
osteophytes, marginal erosions, and synovitis (Fig. 13.3). It may also be considered
a feasible and prompt tool for visualizing inflammation in patients with hand
OA. Conversely, one of the US disadvantages is the inability of the beam to pene-
trate the cortex. Because of joint anatomy, the visualization of the cartilage and
bone damage is mainly limited to its peripheral parts. Overlying osteophytes, which
interfere with the acoustic window, further complicate the assessment. In severely
damaged joints, it may be difficult to determine where an erosion begins and an
osteophyte ends. Most US studies of patients with hand OA reported a high preva-
lence of grayscale synovitis, while potency Doppler activity was less frequent. In
erosive OA, often called “inflammatory” OA, a greater power Doppler activity,
synovial hypertrophy, and joint effusion compared to patients with non-erosive
radiographic OA joints can be found. Synovitis appears to be more prevalent in
joints with active erosions, while the prevalence is lower in joints that have been
remodeled [19, 20].

Fig. 13.3 US scan of the

first carpometacarpal joint
(M: metacarpal bone, T:
trapezius) showing
capsular distension with
effusion (asterisk),
osteophyte and
periarticular calcifications
(arrow)
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 353

13.4.3 Magnetic Resonance Imaging (MRI)

With the use of MRI, OA is now recognized as a disease that affects the entire joint.
Currently, only limited research is available on the prevalence, reliability, and valid-
ity of pathology defined by MRI in hand OA. Common features of hand osteoarthri-
tis MRI can provide a multiplane image of all joint components, including structural
features such as osteophytes, cartilage, erosions/cysts, misalignment, and inflam-
matory features such as synovitis and tenosynovitis (Fig. 13.4). MRI is the only
technique capable of showing bone marrow’s injury, which is an important feature
of structural progression and nonetheless, a source of pain. The prevalence of MRI
pathology in patients with hand OA has been studied in several cohorts, founding a
high prevalence of synovitis based on gadolinium enhancement. Synovitis was also
widespread in joints without radiographic OA, and this is in line with previous
observations in knee OA. However, minimal gadolinium enhancement can also
occur in the population without OA, and therefore synovitis cannot be seen unless
there is an accompanying thickness of the synovium. In the joints of the little fin-
gers, it is also important to be aware of partial volume artifacts that can mimic
BMLs [21].
Haugen et al. recently proposed an extensive preliminary MRI scoring system
with an accompanying atlas for hand OA, validated with good intra- and inter-reader
reliability. Their system includes osteophytes evaluation, JSN, erosions, cysts, mis-
alignment, synovitis, flexor tenosynovitis, BML, and collateral ligament pathology
such as absence/discontinuity at insertion sites. The scoring was developed for the
DIP and PIP joints, and future studies need to confirm whether it can be further
applied to the metacarpophalangeal (MCP) and base of the thumb joints [22].

a b

Fig. 13.4 Coronal T1 (a) and STIR (b) slices of the hand showing advanced trapeziometacarpal
joint osteoarthritis changes with joint space narrowing, joint capsule thickening, and reactive bone
marrow edema
354 A. Barile et al.

13.5 Knee Osteoarthritis

Knee OA is the most common joint disease in the elderly and, overall, is very com-
mon. It is estimated to affect ~12.5% of patients >45 years. The medial femorotibial
joint district is more commonly affected and is usually more severe than the lat-
eral one.

13.5.1 Conventional Radiography (CR)

The hallmarks of knee OA are like the aforementioned for other joints, This includes
joint space narrowing which is usually asymmetric, typically regarding the medial
tibiofemoral and/or the patellofemoral region. JSN <3 mm on weight-bearing knee
radiographs is considered a finding of absolute joint space narrowing with a normal
joint space >5 mm (Fig. 13.5). Compared to non-weight-bearing radiographs,
weight-bearing radiographs evidence a bigger joint space narrowing, hence affect-
ing the radiographic severity.
Plain radiographs are the imaging flagships including follow-up, although there
is a poor correlation between radiographic findings and clinical symptoms. The ini-
tial study of a patient with knee OA suspect should include a Rosenberg view, a PA
radiograph with weight-bearing, and 45° flexion, which is more sensitive in detect-
ing joint space narrowing [23].

a b

Fig. 13.5 Frontal (a) and lateral (b) plain film view in a patient with knee osteoarthritis showing
marked medial joint space narrowing, subchondral bone sclerosis, and osteophytes
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 355

Kellgren and Lawrence first described a grading system in 1957 which was later
adopted as the standard measure for assessing radiographic OA by the World Health
Organization in 1961. The original description was graded as follows:

• Grade 0 (none): absence of X-ray osteoarthritic changes

• Grade 1 (doubtful): doubtful joint space narrowing and possible osteo-
phytic lipping
• Grade 2 (minimal): osteophytes and possible joint space narrowing
• Grade 3 (moderate): moderate multiple osteophytes, definite narrowing of joint
space and some sclerosis, and possible deformity of bone ends
• Grade 4 (severe): large osteophytes, marked narrowing of joint space, severe
sclerosis, and definite deformity of bone ends

Subsequently, methods were used to classify OA individual aspects, such as

osteophytes, JSN, and subchondral sclerosis. However, there are several limitations
associated with both these classifications. Firstly, they predominantly include ordi-
nal measures, with only a limited number of categories. Secondly, the osteophytes’
role is unclear, although their presence is crucial in the classification systems. For
example, despite being related to the presence of pain, osteophytes are not related to
severity and do not seem associated with disease progression. The underlying use of
JSN is the hypothesis that longitudinal joint space reduction is a valid measure of a
reduction in joint cartilage volume [24].

13.5.2 Magnetic Resonance Imaging (MRI)

For OA assessment, standard MR sequences allow morphological and qualitative

evaluation of articular cartilage and other joint structures. In the last years, several
advanced MR imaging sequences and techniques were developed to provide a
global, sensitive, and specific assessment of the joint degenerative processes with
semi-quantitative, quantitative, and compositional analysis methods [25].
Semi-quantitative MR scoring systems are based on the global morphological
evaluation of pathological changes (e.g., alterations of articular cartilage, subchon-
dral bone, fibrocartilages) that affect the functional and structural integrity of the
joint and determine the severity of the disease. These scoring systems are used with
standard morphological MR sequences, especially T2 and PD fat saturated
sequences. Four scoring systems were established for the knee: the Whole Organ
Magnetic Resonance Score (WORMS), the Knee Osteoarthritis Scoring System
(KOSS), the Boston-Leeds Osteoarthritis Knee Scoring (BLOKS), and the MOAKS
(MRI Osteoarthritis Knee Score). Equivalent scores were also created for other
peripheral joints, such as the Oslo Hand OA MRI Score (OHOA-MRI), the Hip
Osteoarthritis MRI Scoring System (HOAMS), and the Scoring Hip Osteoarthritis
with MRI (SHOMRI). Concerning the methodology, in brief, the joint is divided
into several articular compartments/subregions (e.g., medial and lateral tibia, medial

AL GRAWANY
356 A. Barile et al.

a b

Fig. 13.6 Coronal T1 (a) and STIR (b) knee MR images depicting high-grade lateral femoral
condyle and tibial plateau chondropathy

and lateral femoral condyle), and several joint features (e.g., cartilage signal and
morphology, synovitis, subchondral bone) are analyzed and scored according to the
severity of the involvement (Fig. 13.6). Numerous studies validated the reproduc-
ibility of these scoring systems; the MOAKS is currently the most used one for the
knee, bringing together the advantages of these scoring systems. The clinical assess-
ment of semi-quantitative analysis was demonstrated by the presence of some spe-
cific alterations (such as Hoffa synovitis, joint effusion, medial meniscus lesions)
associated with an increased risk of OA radiographic progression. Other studies,
using these transversal and longitudinal comparisons methods of disease evolution,
highlighted how the presence of cartilage damage and the presence of subchondral
edema correlate with an increased risk of prosthetic surgery necessity.
Quantitative MRI assessment provides a more sensitive and specific evaluation
of cartilage’s degeneration degree and it is superior to semi-quantitative techniques
in evaluating structural changes. Three-dimensional (3D), high-resolution sequences
are required to image the bone–cartilage interface and the cartilage surface with
adequate contrast. After image acquisition, the post-processing analysis involves
automatic or manual segmentation of the articular cartilage (that is, the separation
of the cartilage from the underlying bone and adjacent tissues). This data sets and
image reconstructions allow the evaluation of several quantitative features (e.g.,
cartilage thickness, area, volume) as continuous variables. Studies on quantitative
cartilage evaluation showed good inter-operator reproducibility at different degrees
of cartilage degeneration and excellent correlation with the surgical and histological
findings. Quantitative methods have a good correlation with semi-quantitative
results, even if more sensitive and specific in predicting cartilage loss (especially in
small widespread defects using regional analysis); therefore, some authors suggest
a combined use of these techniques. Modifications in the cartilage’s volume and
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 357

thickness were used as an outcome parameter in observational studies regarding

pharmacological treatments (e.g., chondroitin sulfate), physical therapy and reha-
bilitation, and surgical treatment trials. These assessments have become new quan-
titative metric parameters that can be considered as biomarkers, to improve the
prognostic value of conventional disease progression assessments. The necessity of
a dedicated software and the tedious analysis can be considered as a major disad-
vantage to ordinary clinical application.
Articular cartilage is made of chondrocytes which spread within a matrix com-
posed of water and a highly organized reticulum of collagen proteoglycans (PGs)
and glycosaminoglycans (GAGs). Collagen fibers orientation varies from the sur-
face to the deepest calcified zone. In OA, before cartilage fissuration, there is a
progressive disruption of the matrix’s architecture with GAGs and collagen loss and
a consequent increase of water content. Noticeably, these matrix modifications in
the early stages of OA development are not discernible in standard morphological
MRI sequences. Based on the known pathogenesis of joint degenerative processes,
we can appreciate the histological level of biochemical changes in cartilage ultra-
structure, including the reduction of proteoglycans (PGs) and glycosaminoglycans
(GAGs) and the increase in water content, anticipate morphological changes.
Advanced imaging technologies provide information on the ultrastructural and bio-
chemical composition of cartilage to detect and monitor the initial stages of the joint
degenerative processes. MR imaging techniques are in fact based on the cartilagi-
nous ultrastructural components modification (e.g., GAG, PG). In particular, we
consider relaxation times measurements (T2 and T1ρ mapping), sodium imaging,
delayed gadolinium enhancement MRI of cartilage (dGEMRIC) imaging, chemical
exchange saturation transfer imaging of GAG (gagCEST), and imaging and diffu-
sion imaging (DWI and DTI).
T2 and T1ρ mapping: These sequences measure the T1 and T2 relaxation times
(expressed in ms) of molecules present in the tissue. Briefly, T2 relaxation time
reflects the ease of protonic water molecules movement within the matrix. In the
articular cartilage, T2 relaxation times mainly depend on the collagen content of the
extracellular matrix and the orientation of collagen fibers, and higher relaxation
times are correlated with an increased deterioration of the cartilage matrix. The T2
relaxation time is measured as a function of the signal measured in multi-echo SE
and FSE T2-weighted images with mono- or multi-exponential decay curve at the
different echo times (TE). T1ρ mapping is a compositional approach which is sensi-
tive to regional changes in cartilage matrix proteoglycans characterized by continu-
ous resonance RF pulse. Water molecules protons associated with different
macromolecules such as PGs dissipate energy faster than protons of free water mol-
ecules, therefore long T1ρ relaxation times correlate with GAG depletion. The main
disadvantages are given by issues related to the high SAR (due to the application of
long-lasting RF pulses) and long acquisition times. A fundamental advantage of
relaxation mapping sequences is that contrast medium administration is not neces-
sary. Both T1ρ and T2 mapping can be assessed both qualitatively with colorimetric
scale and quantitatively by ROI positioning. Fibrocartilages (e.g., menisci) can be
studied using T1ρ and T2 mapping since they are composed of collagen,
358 A. Barile et al.

proteoglycans, and water as well. Ultrashort time echo (UTE) T1 and T2 mapping
sequences can be used to analyze low intrinsic relaxation time tissues such as
menisci, tendons, deep layers of cartilage, deep cartilage areas where non-UTE
imaging is not sensitive enough.
Sodium imaging (23Na): This compositional imaging technique is based on the
detection of sodium, the positive cation linked to the negatively charged glycosami-
noglycan (GAG) of the cartilage’s matrix. More specifically, the sodium concentra-
tion within the cartilage matrix is directly correlated to the concentration of GAG
and hence to proteoglycans. The main strength of sodium (23Na) MRI is in fact the
high specificity to proteoglycan. As in relaxometry and diffusion imaging, exoge-
nous contrast medium administration is not required to obtain sufficient tissue con-
trast. However, in vivo sodium imaging of cartilage limits includes low intrinsic
SNR, caused by the low 23Na MRI signal compared to the one from protons.
Delayed gadolinium enhancement MRI of cartilage (dGEMRIC): Contrast
medium (gadolinium), injected intravenously is necessary for this imaging method.
The scan is performed 60–90 min after injection, to allow diffusion of the contrast
medium into the cartilage matrix. Gadolinium is negatively charged and is rejected
by positively charged GAGs in cartilage, while in case of cartilage matrix degrada-
tion, the amount of contrast in cartilage tissue will be increased in an inversely
related manner. The dGEMRIC technique showed high sensitivity and specificity;
the routine clinical use is limited by the need for high doses of gadolinium.
Chemical exchange saturation transfer imaging of GAG (gagCEST): This
sequence is based on the constant labile protons transfer between solutes (in the
case of cartilage, GAGs) and water. The difference between water–water transfer
and water–GAG transfer is measured as the magnetic transfer ratio. The signal
obtained from the energy transferred after radiofrequency proton saturation is pro-
portional to the concentration of GAG in the tissue. Unfortunately, strong magnetic
fields (7 T scanners) are required to obtain sufficient signal, thus widespread use,
even in the research field, is currently limited.
Compositional MRI sequences were widely explored in literature for the assess-
ment of cartilage, menisci, and tendons in degenerative osteoarthropathies of periph-
eral joint, mostly the results concerning the use of T2 mapping on knee articular
cartilage. The most important results were obtained by longitudinal studies on disease
progression, demonstrating the association and the predictive value of compositional
cartilage changes with potential risk factors such as age, sex, BMI, sport, injuries,
surgery. Imaging with advanced MRI sequences is becoming increasingly important
in cartilage’s degeneration studies. Because of the recent widespread development of
disease-modifying drugs and regenerative therapies (e.g., platelet-­rich plasma, hyal-
uronic acid, chondrocyte implantation), MRI is also crucial in assessing new therapies
for OA prevention or for approaches to avoid progression. As the efficacy is closely
connected with early treatment, their use requires suitable biomarkers to provide an
early diagnosis and detect signs of progression during treatment. Advanced MRI find-
ings can represent, in this scenario, a powerful tool to understand how to better treat
and manage OA and this will possibly allow the creation of a “target-based therapy”
for every single component of the cartilage matrix [26].
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 359

13.6 Hip Osteoarthritis

The hip is the third most common joint affected by osteoarthritis after the knee and
the hand. Women are more commonly affected than men. The reported prevalence
varies in different studies and is also subject to geographic distribution. The risk of
symptomatic hip osteoarthritis in people reaching the age of 85 is estimated up to
25% in some regions. Attributes, characteristics, or exposures that increase the like-
lihood of developing hip osteoarthritis are advanced age, obesity, genetics, repeti-
tive stress and mechanical overload, acetabular dysplasia, femoroacetabular
impingement, epiphysis capital femoral slip, Perthes disease, and trauma.
Patients usually experience slowly progressive hip pain or hip-related groin pain
that radiates into the thigh, gluteus, or knee. Pain can be worse at night, during rest,
or after strenuous activity, reducing motion and limiting the walking distance. It can
be associated with morning stiffness or after rest. Other symptoms include joint
locking, grinding and instability, fatigue, and pain-related psychological distress.
Occasionally, a striking discrepancy is observed between radiological findings and
clinical symptoms, in fact, patients with pronounced radiological changes have only
mild symptoms, while patients with minor radiographic findings complain of acute
pain. Therefore, OA diagnosis and, above all, the therapeutic indication, should be
made only after both radiological and clinical evaluation [27].

13.6.1 Conventional Radiography (CR)

Plain hip radiographs are inexpensive, widely available, and readily obtainable, and
they allow a prompt OA assessment.
For hip osteoarthritis definition, an anteroposterior radiograph of the hip and a
lateral cross or lateral view of the frog leg are crucial. As for other joints, reliable
radiological indicators are joint space narrowing, subchondral sclerosis, subchon-
dral cysts, and the formation of osteophytes. Narrowing of the hip joint space
≤2 mm or <2.5 mm or the combination of joint space narrowing and the presence
of osteophytes, especially in the absence of elevated inflammatory markers (e.g.,
ESR < 20 mm/h), can be used as an indicator of osteoarthritis [28]. In addition,
loose bodies (<10), joint deformities, and subluxations can be observed. In advanced
stages of OA, the head of the femur is deformed assuming a cylindrical or mushroom-­
shaped form. The classic radiological sign of osteoarthritis is the joint space narrow-
ing, particularly seen on anteroposterior radiographs taken while the patient is
standing (Fig. 13.7). When joint space and cartilage narrowing occurs, the femoral
head changes its position relatively to the socket. Femoral head migration is primar-
ily cranial (combined with anterolateral or anteromedial motion) but occasionally
axial or medial. This description of the migration is based on what can be observed
in the anteroposterior X-ray image. Radiographic signs of medial-caudal migration
of the femoral head are the joint space narrowing in the medial joint with subchon-
dral sclerosis and the osteophytes formation in case of laterocranial joint space
enlargement. The orthopedic surgeon gives joint replacement indication without
360 A. Barile et al.

Fig. 13.7 Radiographic

findings in a patient with
bilateral hip osteoarthritis,
with joint space narrowing,
subchondral sclerosis, and
acetabular osteophytes

regard to the migration’s direction. However, as various types of migration lead to

leverage ratios modifications, geometric hip joint reconstruction using endopros-
thetics goals include center of rotation normalization, anatomical offset reconstruc-
tion, and equalization of the leg length [29].
The radiological classification systems most commonly used for hip osteoarthri-
tis assessment are: the Kellgren and Lawrence score, the Croft score, and the Tönnis
classification. Although they are all affected by subjectivity, the Kellgren and
Lawrence score is apparently the most reliable.
Another semi-quantitative method, which does not provide a grade definition of
OA, but classifies several features such as the formation of femoral and acetabular
osteophytes and the narrowing of the superior and medial joint space is the OARSI
atlas. According to this atlas, a score from 0 to 3 is attributed to the presence and
quantity of marginal osteophytes at the level of the upper acetabular side, upper
femur, and lower femur, and to the presence or absence of osteophytes on the lower
acetabular side.
The narrowing of the joint space is marked 0–3 points on both the superior and
medial side. Additional scores (presence/absence) are used for the evaluation of
acetabular subchondral cysts, subchondral femoral cysts, femoral subchondral scle-
rosis, flattening of the femoral head, and thickening of the medial femoral calcar
(buttress).

13.6.2 Computed Tomography (CT)

CT exams with multiplane and three-dimensional reconstructions have now replaced

most of X-ray views and can easily be used even in patients with limited range of
motion. The representation of subchondral sclerosis, cyst formation, and small
osteophytes or also the evidence of loose bodies is more accurate than projection
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 361

a b

Fig. 13.8 CT (a) and STIR MRI (b) of the hip joint showing osteoarthritis changes with subchon-
dral geodes, bone marrow edema, and joint effusion

radiography (Fig. 13.8). Another common CT indication is the preoperative diagno-

sis of hip socket abnormalities or post-traumatic conditions in presence of metal
devices which is done by assessing the amount of acetabular bone stock and check-
ing for misalignment or deformity of the proximal femur. The orthopedic surgeon
requests the available bone stock localization which allows a safe endoprosthetic
anchoring of the implant components. For example, for dysplastic osteoarthritis
with high femoral head dislocation and neo-joint, the question will be how large the
original acetabulum is and whether there is enough sized bone stock available to
firmly anchor the planned socket. In case of axial misalignment and deformity of
the proximal femur (e.g., after corrective osteotomy on the proximal femur), three-­
dimensional CT imaging is essential in planning the multiplane corrective osteot-
omy if needed. The objective of this procedure is to anchor the shaft components in
the femur with a correct alignment and with a sufficient anchoring surface [30].

13.6.3 Magnetic Resonance Imaging (MRI)

MRI is most commonly indicated for the evaluation for surgery where there is a
large discrepancy between clinical symptoms and osteoarthritis degree of severity
in X-ray images. The orthopedic surgeon examines the MRI to judge the labral and
cartilage damage, the presence of effusion/synovitis, and of subchondral and paral-
abral cysts. When there is hip joint OA, the primary significance of MRI is to show
both early signs of arthritis (joint cartilage, labrum) and active signs of osteoarthri-
tis. Additionally, MRI is also capable of showing any associated muscle atrophy.
Further indications are to evidence active osteoarthritis (bone marrow edema, syno-
vitis, effusion), as well as assessing the cartilage prior to hip arthroscopy (or the use
of endoprostheses). On selected patients MRI is suggested for preoperative
362 A. Barile et al.

Fig. 13.9 STIR coronal

(a) and T1-W axial (b) a
MRI images in a patient
with right hip osteoarthritis
showing the presence of
fluid joint distension and
synovial chondromatosis

evaluation of actual cartilage damage in joint-preserving periacetabular osteotomy.

In addition to the 3D visualization of the acetabular and femoral head-neck mor-
phology, MRI allows the evaluation of a large variety of tissue abnormalities not
only of the cartilage and acetabular labrum but also of the bone marrow, ligaments,
and synovium. Loose bodies in the form of cartilage and bone peeling are also a
typical sign of osteoarthritis and are easier to detect with MRI than on X-rays
(Fig. 13.9) [31].
Images should be acquired in sagittal and oblique coronal axial planes. Radial
and axial images are of additional utility for femoral head-neck junction and acetab-
ular anatomy evaluation in the case of femoroacetabular impingement associated
with cam and/or pincer morphology. For simplified acquisition, 3D imaging and
secondary oblique and radial reconstructions are recommended.
The semi-quantitative scoring systems based on MRI most commonly used are
the HOAMS, HIMRISS, and SHOMRI scores. The HOAMS evaluates a variety of
hip joint characteristics such as condral lesions, bone marrow lesions, subchondral
cysts, osteophytes, labral lesions, synovitis, and joint effusion, as well as friction,
dysplasia, intra-articular bodies, labral hypertrophy, paralabral cysts, femoral hernia
fossa, insertional tendonitis, and/or bursitis. The SHOMRI score evaluates fewer
features including: condral loss, bone marrow edema pattern, subchondral cysts,
labral anomalies and cysts, intra-articular loose bodies, joint effusion or synovitis,
and ligament abnormalities. For the evaluation of active disease, HIMRISS (hip
inflammation MRI scoring system) was described, which focuses on the active
inflammatory aspects of osteoarthritis and measures only three characteristics of the
disease, namely bone marrow injury, effusion, and synovitis [32].
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 363

13.7 Foot and Ankle Osteoarthritis

About 1% of the world’s adult population is affected by OA of the ankle, which

results in pain, dysfunction, and reduced mobility. The mental and physical disabil-
ity associated with end-stage ankle OA is at least as severe as that associated with
end-stage hip OA. While the etiology of OA of the hip and knee is well understood
and highlighted in numerous clinical studies, research relating to OA of the ankle is
limited. Knowledge and analysis of the underlying etiology are important in select-
ing the best treatment strategy and are critical to achieving long-term satisfactory
results and avoiding postoperative complications. Unlike the hip and knee, the ankle
joint is rarely affected by primary OA. Numerous clinical and epidemiological stud-
ies have identified prior trauma as the most common cause of OA in the ankle
instead. Patients with post-traumatic OA are generally younger patients than the
ones with the primary form. An epidemiological study of patients with disabling
OA of the hip, knee, and ankle showed that 1.6% of patients with hip OA, 9.8% of
patients with knee OA, and 79.5% of patients with ankle OA had a verified history
of 1 or more joint injuries. Saltzman and his colleagues evaluated 639 patients with
end-stage painful OA in the ankle (Kellgren grade 3 or 4), founding that 70% of
patients had post-traumatic OA, 12% had rheumatoid OA, and 7% had primary
OA. While rotational ankle fractures were identified as the most common reason for
post-traumatic ankle OA, previous ligament injuries have also been found to be a
cause of ankle OA. Secondary OA has also been associated with a variety of under-
lying diseases or disorders, such as rheumatoid disease, hemochromatosis, hemo-
philia, gout, neuropathic diseases, avascular talus necrosis, osteochondral lesions,
and postinfectious arthritis [33, 34].
A 4-film series of conventional radiographs including anteroposterior and lateral
views of the foot, mortise view of the ankle, and Saltzman view of the hindfoot can
be routinely performed for radiographic evaluation of the ankle and foot OA. Only
foot and ankle X-rays are acceptable because non-weight bearing X-rays are often
misleading. Additionally, standing views can help standardize radiographic tech-
niques, allowing for more reliable comparison of inter and intra-individual radio-
graphs. Ankle alignment must be analyzed on all 3 levels: supra-malleolar,
intra-articular, and infra-malleolar. Supra-malleolar alignment of the ankle should
be assessed in the coronal and sagittal planes by measuring the distal medial tibial
angle and the anterior distal tibial angle, respectively. Measurement of the distal
medial tibial angle depends on the radiographic technique. Saltzman’s view should
be used to assess infra-malleolar alignment. Several measurement techniques can be
applied to quantify the infra-malleolar hindfoot alignment. Firstly, the angle between
the longitudinal axis of the tibia and the heel axis can be measured as suggested by
Cobey and Reilingh. Takakura and colleagues used weight-bearing radiographs to
classify OA of the ankle into four stages. For clinical use, investigators simplified
this classification, describing stage 1 as early, stages 2 and 3 as intermediate, and
stage 4 as late [35].
364 A. Barile et al.

13.8 Interventional Radiology in Osteoarthritis

Interventional radiology can offer a wide range of therapeutic procedures also in

musculoskeletal pathology through ultrasound, CT, and MRI guidance. Based on
the above evidence, the synovium—that is synovial inflammation—has become one
of the main therapeutic targets not only for inflammatory arthropathies but also in
degenerative arthrosis. Corticosteroids are arguably the most widely used anti-­
inflammatory drugs. The possibility, through image guidance, of direct intra-articu-
lar injection of drugs is the key to maximizing therapeutic effects while minimizing
known systemic side effects. In addition to intra-articular administration, ultrasound
imaging guidance is useful for intra-bursal and peri-tendinous assessment, where
corticosteroids may have an anti-inflammatory action on synovial tissue. The imag-
ing guide also helps minimize other risks of unguided corticosteroid infiltration,
such as tendon ruptures. Injection of hyaluronic acid (HA) is another interventional
procedure that can be suggested for degenerative joint disease (i.e., osteoarthritis)
but mainly for the synovium. Hyaluronic acid is a glycosaminoglycan consisting of
highly hydrophilic chains of d-glucuronic acid and N-acetylglucosamine. There are
numerous types of hyaluronic acid on the market, which are distinguished mainly
by their molecular weight. Hyaluronic acid with low molecular weight, able to bind
to binding proteins (hyaladerin) and to the CD44 receptor, acts mainly with a bio-
logical effect of viscoinduction (i.e., by stimulating the endogenous production of
HA). Those with high molecular weight, however, have a lower biological effect
while carrying out a powerful viscous supplementation action, thanks to their rheo-
logical properties. Although the meta-analysis highlights the available studies het-
erogeneity, intra-articular injections of HA appear to be effective in the treatment of
arthritic pain (mild to moderate OA) in both the knee and the hip. The size of the
results on pain resolution varies between studies, peaking at 8 weeks (superior to
corticosteroids). Cross-linked (high molecular weight) products have greater pain
efficacy than linear HA and there is evidence to support the efficacy of HA also
regarding functional improvement (level 1B). In all guidelines, use is recommended
for osteoarthritis management of second-line treatment in symptomatic patients
after conservative therapy (NSAIDs). Injection of platelet-­rich plasma is another
therapeutic tool that we can consider. This product, consisting of a platelet ultrafil-
trate, carries out its action through various growth factors (PDGF, TGF-B, EGF,
CTGF) released with their anti-inflammatory and trophic action on various joint
tissues. There are several in vitro and clinical evidence that intra-articular injection
of PRP can exert a positive influence in patients with knee cartilage degeneration
and OA and that it may have greater and longer efficacy than HA in improving pain
and joint function [36, 37].
13 Osteoarthritis in Appendicular Skeleton in Geriatric Patients 365

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Metabolic Bone Disease in Geriatric
Patients 14
Maria Pilar Aparisi Gómez, Francisco Aparisi,
Giuseppe Guglielmi, and Alberto Bazzocchi

14.1 Introduction

As humans age, the lean components of the organism such as total body water,
organ mass, mineral bone, and skeletal muscle decrease, while total body fat
increases, with an associated redistribution: it becomes more abundant in the
abdominal region than in peripheral locations [1].
The process of aging involves endocrine and metabolic alterations, but besides,
an increasingly sedentary lifestyle generates a positive imbalance between intake
and use of energy [2, 3]. Aging is characterized by a low-grade chronic inflamma-
tory status known as “inflammaging” [4].
Due to the role fat has as an endocrine organ, the increase in body fat and the redis-
tribution of the fat in geriatric population have been demonstrated to be associated
with risk factors for non-insulin-dependent diabetes and cardiovascular disease [5].

M. P. Aparisi Gómez
Department of Radiology, Auckland City Hospital, Auckland, New Zealand
Department of Radiology, IMSKE, Valencia, Spain
e-mail: [email protected]
F. Aparisi
Department of Radiology, Hospital Nueve de Octubre, Valencia, Spain
G. Guglielmi
Clinical and Experimental Medicine, University of Foggia, Foggia, Foggia, Italy
e-mail: [email protected]
A. Bazzocchi (*)
Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 367
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_14
368 M. P. Aparisi Gómez et al.

The loss of mineral contents in bone and structural changes are a major risk for
morbidity, need for institutionalization, and mortality. Sarcopenia, with a decrease
in muscle mass and function, has been associated with impaired immunity and func-
tional status [6, 7].
The three tissues (fat, muscle, and bone) have a very close relationship, and
therefore analysis and evaluation should be approached in a combined way.
Osteoporosis is described as a systemic bone disease characterized by low bone
mass and microarchitectural deterioration of bone tissue, with a consequent increase
in bone fragility and susceptibility to fracture [8].
Osteoporosis as an entity may result either from defective skeletal development
leading to a start point of low bone mass and quality, or from an imbalance in cou-
pling, with an increase in the resorption of bone, exceeding formation.
The most prevalent cause for osteoporosis and therefore statistically the most
common cause for fragility fractures is postmenopausal osteoporosis, which is
inherently linked to aging in women; however, any situation where there is osteopo-
rosis, either primary or secondary to several conditions, in both genders, increases
the risk of occurrence of a fragility fracture. Postmenopausal osteoporosis develops
after a decrease in estrogen levels following menopause.
Senile osteoporosis is another primary cause for osteoporosis and affects both
genders. This is age related, occurring in individuals older than 75 years. Bone for-
mation is impaired through a mechanism of decreased renal production of 1,25
dihydroxyvitamin D with a subsequent drop in calcium absorption from the diet that
results in secondary hyperparathyroidism [9].
The most prevalent type of fragility/insufficiency fracture is the vertebral com-
pression fracture, but the effect of osteoporosis on the skeleton is systemic, and
there is increased risk of almost all types of fractures. Other frequent locations for
insufficiency fractures are the pelvic girdle and the proximal femur. Locations such
as the femoral diaphysis, tibia, fibula, and calcaneus and metatarsal bones are less
frequent and can represent a diagnostic challenge [10].
In the bone, the aging process is characterized by a progressive accumulation of
adipose cells within the bone marrow (BM). The role of marrow adipose tissue
(MAT) as a component of the BM microenvironment has been thoroughly investi-
gated in the last few years. A growing amount of evidence shows that there is an
inverse association between MAT content and both bone mineral density (BMD)
and bone integrity [11].
In this chapter, we aim to summarize the current knowledge on changes in bone
metabolism occurring in the elderly and review the possibilities of assessment that
each one of the imaging techniques offers for the adequate assessment of bone min-
eral density in the geriatric population.
The contents of this chapter need to be taken into consideration together with the
chapter on body composition in geriatric patients. The effects of aging on fat and
muscle are extensively reviewed in a dedicated chapter, but it is important to
acknowledge the close relationship and interrelation existing between all
components.
14 Metabolic Bone Disease in Geriatric Patients 369

14.2 Changes in Bone with Aging

14.2.1 Menopause

Estrogen has a very important role in normal physiologic remodeling, and its defi-
ciency after menopause results in remodeling imbalance with an increase in bone
turnover. The imbalance leads to a progressive loss of trabecular bone first (most
metabolically active) and then progressively cortical bone [9].
Menopause is defined by the World Health Organization (WHO) as the “perma-
nent cessation of menstruation resulting from the loss of ovarian follicular activity,”
initiated by the decline in estrogen and progesterone production and by increasing
follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. Twelve
months of consecutive amenorrhea are necessary to establish the onset of menopause.
The perimenopausal stage is defined as the time elapsed from the commencement of
the first clinical signs (cycle irregularity, known as “menopause transition”) and a year
after the last period. Elevation of early follicular phase FSH is a clinical marker of
reduced ovarian reserve and decreased response of the ovary to ovulation induction.
The endocrinology of menopause is complex and results from changes in the
pituitary-ovarian axis with age in regularly cycling women. The decline in follicle
numbers results in a decline in ovarian hormone production, which alters the pitu-
itary feedback.
The rise in serum FSH is accompanied by minimal changes in circulating levels
of LH. Concentrations of androgens appear to be lower in the postmenopausal sta-
tus, it is thought that this happens as a function of increasing age during the repro-
ductive years as opposed to a consequence of menopause as such. By 12–24 months
after menopause, the levels of estradiol in serum are normally <80 pm/L, compared
with mean values of approximately 550 pm/L in premenopausal stage. The levels of
FSH are 10–15 times higher than the levels that would be usual in earlier follicular
phases in young women. LH levels are approximately 3 times higher. Plasma testos-
terone levels decrease from ~1 to 0.6 nmol/L. There is an approximately 40%
decrease in the ovarian androstenedione production, dehydroepiandrosterone sul-
fate (DHEAS) production declines in a linear fashion with age, not related to post-
menopausal status as such [12].
The decrease in estradiol levels has different systemic effects and can contribute
to the development of different disorders: osteoporosis, cardiovascular risk, changes
in mood, and mental health.

14.2.2 Calcitriol

Senile osteoporosis is another primary cause for osteoporosis and affects both gen-
ders. This is age related, occurring in individuals older than 75 years. Bone forma-
tion is impaired through an alteration in the metabolism of vitamin D. In this context
the cortical as well as the trabecular bone is affected [9].
370 M. P. Aparisi Gómez et al.

Vitamin D, as its major metabolite, 1,25-dihydroxyvitamin D or calcitriol, plays

a role in the homeostasis of bone, muscle, and adipose tissue through life, not only
during growth, but also in aging.
In the elderly, levels may be impaired, due to various reasons, which include
reduced intake, decreased skin production of cholecalciferol (first precursor of
active vitamin D), possibly due to lower sun exposure, decrease in the activity of
liver hydroxylases with a drop in the conversion to calcidiol, and (25-­hydroxyvitamin
D) and decrease in the activity of renal hydroxylases with a drop in the conversion
to calcitriol [13].
Calcitriol is relevant in the function of proteins that transport calcium, and as a
result of its decrease, calcium absorption is decreased.
There is a strong correlation between low calcidiol concentrations and increasing
levels of obesity [14].
Obese individuals, even when controlling for sunlight exposure, are significantly
more likely to have low concentrations of calcidiol, which reflects inadequate vita-
min D status [15].
Inadequate vitamin D status can increase adipogenesis by promoting higher
parathyroid hormone (PTH) secretion, which increases the influx of extracellular
calcium into adipocytes, promoting adipogenesis. In a similar way, low calcium in
serum may promote an increase in the circulating calcitriol and PTH, with the same
increased adipogenesis result [16, 17].
Calcitriol is essential for normal bone turnover and maintenance, as well as for
the metabolism of calcium, phosphorus, and magnesium [14]. A decrease in cal-
citriol disturbs calcium homeostasis and impairs bone health, which leads to an
increase in fracture incidence [18]. Despite this, the recommendations for vitamin
intake and adequate serum concentrations of calcidiol are still controversial [19].
Inadequate levels of vitamin D have also been associated with sarcopenia,
decreased grip strength, and impaired functionality in older adults [20, 21].
Studies have demonstrated that the inverse relationship between vitamin D status
and PTH concentration is associated with compromised muscle mass and strength,
as well as diminished physical function [20, 21].
A study in the elderly demonstrated that low calcidiol and high PTH increase the
risk of sarcopenia, reflexed in low muscle mass and reduced hand grip strength [22].
Another study has found that patients with insufficient calcidiol and low BMD
are also more likely to develop sarcopenia [20].

14.3 Interaction Among Bone, Muscle, and Fat

In the past, it was believed that obesity had a protective role in bone and in muscle,
providing mechanical load and therefore stimulus for their maintenance. Fat is as
well a source of estrogens, which are beneficial to maintain bone health, reducing
bone resorption, contributing to muscle repair and regeneration and reducing adipo-
genesis [23–25].
14 Metabolic Bone Disease in Geriatric Patients 371

However, some concepts have shifted. Fat has been seen to act as an endocrine
organ, releasing hormones such as leptin and releasing cytokines, which are proin-
flammatory agents [26]. In particular, visceral fat (VAT) has a negative impact on
bone and muscle [27]. VAT secretes proinflammatory cytokines such as tumor
necrosis factor-alpha (TNF α), interleukin 1 and 6 (IL-1 and IL-6), and even
C-reactive protein in high inflammatory status [28]. These factors promote and sus-
tain low-grade chronic inflammation, which in turn causes derangement of all three
tissues simultaneously and causes more fat deposition, perpetuating the problem
[27, 28].
Weight gain in older adults leads to greater visceral fat accumulation and long
term impairments in bone and muscle as a consequence.
A study performed in 500 healthy women demonstrated that body fat higher than
33% was negatively correlated to femoral neck bone mineral density (BMD), and if
this increased to 38%, it was negatively correlated to BMD in the lumbar spine and
total-body BMD [29].
Another study identified a cut off of 38.3% body fat as the inflection point where
the slope of the relation between visceral fat and percent body fat increases signifi-
cantly [30]. This disputes the concept that obesity is protective for bone health,
especially for women, but the relationship between obesity and bone is ultimately
of complex nature [31], and more research is needed to determine the threshold in
which body fat becomes harmful for bones and muscle [29], as we will review when
addressing the topic of frailty.
The amount of bone marrow adipose tissue (MAT) increases with aging, in obe-
sity and osteoporosis. MAT appears to reduce osteoblast and osteoclast activity,
slowing down bone turnover (which may be beneficial in some cases like meno-
pause) and decreasing the rate of bone accrual [32]. A negative correlation between
MAT and BMD has been proven [33]. However, it is still confusing whether the
relationship between MAT and osteoporosis is causative or correlative [32].
It is clear that MAT has a role in bone health, through its paracrine and endocrine
interaction with the other components of bone. There is evidence that the bone mar-
row stem cells (precursors of adipocytes and osteoblasts) may favor adipogenic
differentiation in the presence of excessive adiposity, and this is one of the reasons
osteoporosis has been labeled as the “obesity of bone” [34] and increased adipogen-
esis in the marrow “osteosteatosis” [35].
The MAT–bone interaction is a fertile area of research. The development of
imaging, and more especially MR based techniques has unlocked numerous
pathways to assess and quantify MAT and thus set the ground to carry out stud-
ies to further elucidate the implications of MAT in physiologic and pathologic
conditions [36].
A prospective study in a population of Korean women demonstrated that post-
menopausal women with higher VAT levels lost significantly more lean mass over a
period of 27 months than women with lower VAT levels. The decrease in VAT did
not result in a parallel change in BMI, which suggested that fat was replacing the
lost muscle tissue and possibly infiltrating it [27, 37].
372 M. P. Aparisi Gómez et al.

Aging in skeletal muscle involves fat deposit, in the form of intra- and extra-­
myocellular adipocytes, known as myosteatosis. This is seen in older women, even
if they are not obese [38], but can also be seen in younger individuals [39].
Myosteatosis has been considered the “obesity of muscle” [35].
The role of proinflammatory cytokines such as TNF α and IL-6 in muscle wast-
ing and their elevated serum concentration in sarcopenia and sarcopenic obesity has
been established [40]. Additionally, muscle mass is the main determinant of resting
metabolic rate, and loss of muscle would in turn also promote weight gain and fat
accumulation.
In this way, it is easy to see how muscle and bone loss and accumulation of VAT
with aging, aggravated by overall excess of adiposity are part of a cycle where
increased inflammation from visceral fat favors sarcopenia and osteopenia, pro-
motes obesity and as a consequence, greater fat accumulation.
Although fat infiltration of bone and muscle is a part of normal aging, its eleva-
tion in an obesogenic environment exacerbates loss of bone and muscle. The
increase in MAT and myosteatosis, combined with the age related loss of bone and
muscle mass contributes even more to loss of bone and muscle and therefore strength
and overall functionality [38, 41].
Loss of functionality and mobility increases the risk for falls and fractures.
Besides, processes like myosteatosis lead to the development of disorders like dia-
betes, in which the risk of falls is increased, secondary to impaired vision or neu-
ropathy [11, 38].
All this explains the increased risk of frailty in older adults, in cases of osteosar-
copenic obesity and of osteopenic obesity and sarcopenic obesity [42, 43].
Older women suffering from any of these conditions were inferior in several
functional performance measures to only obese counterparts and those suffering
from osteosarcopenic obesity showed significantly poorer performance in hand grip
strength, balance, and walking speed, compared to each one of the other groups [43].
Chung et al. found in a study on older adults that sarcopenic obesity put them at
greater risk of osteoporosis, and the physical decline from sarcopenia appeared to
promote greater loss of bone [44]. The physical decline from any of the conditions
may easily aggravate other declines, ultimately leading to osteosarcopenic obesity.
Overall changes in body composition, leading to impairments in bone, muscle,
and fat tissues have to be taken into consideration when evaluating the health of the
elderly.

14.4 Bone as Endocrine Organ

Osteoblasts secrete osteocalcin (bone gamma-carboxyglutamic acid (Gla) pro-

tein), which is largely incorporated into the extracellular bone matrix (hydroxy-
apatite), but a small amount remains in serum and is used as an indicator of bone
formation [45].
Most of the osteocalcin is carboxylated with vitamin K dependent enzymes and
as a result of this process it can bind calcium within the hydroxyapatite matrix and
stabilize the bone [45]. In cases in which activity of the enzyme is impaired, as in
14 Metabolic Bone Disease in Geriatric Patients 373

low vitamin K status, often present in the elderly, there will be an excess of under-
carboxylated osteocalcin which will not bind to hydroxyapatite and therefore less
bone stabilization, resulting in bone loss. Osteocalcin also stimulates the secretion
of adiponectin from fat cells. Some studies demonstrated that adiponectin had a
negative impact on bone mass by decreasing osteoblast proliferation [46, 47] but
other studies showed that through the same pathway, adiponectin inhibited osteo-
clastogenesis [48, 49].
Undercarboxylated osteocalcin in serum was shown to stimulate pancreatic beta
cell proliferation and insulin secretion and thus positively contribute to modulate
energy metabolism [50].
Mounting evidence on systemic hormonal actions of osteocalcin have gained it
the consideration of an osteokine [26].

14.5 Consequences of the Changes in Bone with Aging

14.5.1 Fragility Fractures

Hip, vertebral, and wrist fractures are the most frequent fractures associated with
osteoporosis. The effect of osteoporosis is systemic, though, so there is increased
risk for almost all types of fractures.
The combined lifetime risk for a hip, forearm, and vertebral fracture is
approximately 40%, which is equivalent to the risk of developing cardiovascular
disease [51].
Fragility fractures due to osteoporosis are one of the most substantial challenges
to public health. The World Health Organization considers osteoporosis to be sec-
ond to cardiovascular risk as a critical health problem.
Approximately 1 in 3 women and 1 in 5 men over the age of 50 will have a fragil-
ity fracture in their remaining lifetime, as per data in Caucasian populations, from
the International Osteoporosis Foundation [52].
In 2000 there were an estimated nine million new osteoporosis fractures, of
which 1.6 million were at the hip, 1.7 million were at the forearm, and 1.4 million
were clinical vertebral fractures. Europe and the Americas accounted for 51% of all
these fractures, while most of the remainder occurred in the Western Pacific region
and Southeast Asia.
In 2006 it was estimated that osteoporosis caused more than 8.9 million fractures
annually worldwide, resulting in an osteoporosis fracture every 3 s [53].
In patients with a hip fracture, it is estimated that up to 20% will die within the
following year due to associated morbidity, with a mortality at 5 years 20% greater
than expected, and approximately 20% will require permanent care [54] (Fig. 14.1).
Patients with vertebral fractures have less severe complications, but these are
more frequent, and approximately only 30% of them come to clinical attention [55].
In these cases there is substantial disability from pain and generally increased tho-
racic kyphosis.
Vertebral fractures have a prevalence of about 35–50% among women over
50 years of age (postmenopausal status) [56], frequently occur in absence of a major
374 M. P. Aparisi Gómez et al.

Fig. 14.1 Subcapital femoral neck fracture of the right hip. These fractures normally result from
a fall from height in the context of osteopenia or osteoporosis. In patients with a hip fracture, it is
estimated that up to 20% will die within the following year due to associated morbidity, with a
mortality at 5 years 20% greater than expected, and approximately 20% will require permanent
care. The main radiographic features of osteoporosis consist of increased bone radiolucency, corti-
cal thinning, and changes in the trabecular pattern, all visible on this radiograph

trauma and may be asymptomatic [57], and increase the risk of a new incidental VF
and other fragility fractures. Individuals with a pre-existing VF have a four- to five-
fold increase in risk of sustaining a new VF, the risk increases with the number of
prevalent fractures at baseline and is BMD-independent [56]. Conventional radiog-
raphy and DXA represent the techniques of choice for VFs detection [57].
Wrist fractures increase almost twofold the risk of subsequent hip or vertebral
fractures, but also the risk of a new forearm fracture is increased by 3.3 times, and
other skeletal fractures by 2.4 times [58].
Humeral fractures, which are the third most common type of fracture in people
over 65 years, have been associated with a higher risk of hip fractures more than 5
times in the following year [59].
Fractures at the foot or ribs were seen to double the risk of hip, vertebral, fore-
arm, and other types [58].
The existence of an insufficiency fracture is an indication for treatment of
osteoporosis.

14.5.2 Frailty

Physical frailty is recognized as a geriatric syndrome, which has become a relevant

concern in public health worldwide, with global population aging [60, 61]. The
most widely used definition of frailty includes the presence of three of the following
14 Metabolic Bone Disease in Geriatric Patients 375

indicators: muscle strength loss, slowness, fatigue, low physical activity, and body
weight loss [62].
Frail older adults are at increased risk of falls, hip fracture, disability, and mortal-
ity [63]. Evidence that body weight is positively associated with bone health in
older adults is increasing [25]; there is also evidence that lean and fat masses, con-
stituting 95% of body weight, might have a different relationship with bone
mass [64].
The potential consequences of body-composition change in frail older persons
should be put both in the context of bone health and with regard to risks of osteopo-
rotic fractures. Frail people have lower muscle mass and higher fat mass than non-­
frail people, but osteoporosis is highly prevalent in the elderly population.
Derangements in inflammatory, endocrine, coagulation, and metabolic systems
should be individually assessed in frail adults and not allow for generalization in
comparison with non-frail aging populations [65, 66]. Zaslavsky et al. demonstrated
that adiposity in the context of frailty has a different impact on survival than the one
that can be observed in non-frail population [67]. A recent study from the same
group showed that appendicular, trunk, and total body fat, as well as lean mass
indexes, are significant determinants of total hip BMD in frail women. Higher lean
and fat mass indexes are associated with lower risks of hip fractures, and whole-­
body fat is the only index to retain indirect association, independently of total hip
BMD. Change over time in body-composition indexes was not a significant deter-
minant of bone health in older women with frailty [68]. These data confirm previous
studies showing an association between whole-body and abdominal fat mass mea-
sures and lower risks of hip fracture. The association was independent of BMD,
indicating that central adiposity might be informative in predicting fractures over
and beyond BMD [69]. In summary, central adiposity may have some benefits for
bone health in the context of frailty, and this should be put in the balance with the
risks of cardiovascular disease.
In studies that included men and women, higher lean mass was not significantly
correlated with hip fractures in models adjusted for total hip BMD [38, 68] which
seems contradictory, given that the association of low BMD and low lean mass on
increasing fracture risk has also been proven [70]. The positive impact of lean mass
on hip fracture risk might thus be channeled through anabolic processes on the bone.
Using the pool of patients from the Women’s Health Initiative, with sample size
of over 120,000 postmenopausal women, Harris et al. concluded that women with
low BMD (T-score <−1), with and without sarcopenia, had a higher risk of fracture
than women with isolated sarcopenia and those considered normal. These results
suggest that sarcopenia does not carry additional risk for fracture in women [71].
The study was limited to fractures around the hip; although women with the combi-
nation of low BMD and sarcopenia had a higher risk of fracture, whereas sarcopenia
alone was not an independent risk factor for fracture in women, the fact that adding
sarcopenia to low BMD resulted in a greater risk suggests that there is communica-
tion between muscle and bone at this site, associated with frailty [72]. The interac-
tion may be mediated by mechanical stimuli, genetic factors, hormonal influences,
and body composition. Total bone mineral content is associated more closely with
376 M. P. Aparisi Gómez et al.

lean tissue than with fat tissue mass, and regional BMD is predicted by changes in
fat tissue mass [73].
A number of mechanisms for the fat–bone relationship in older adults have been
proposed. These include the effect of soft tissue mass on skeletal loading, the asso-
ciation of fat mass with the pancreatic beta cell, and adipocyte secretion of hor-
mones involved in bone metabolism [25]. Additionally, weight reduction may lead
to accelerated rates of bone loss in postmenopausal women. In a large study that
also used data across the Women’s Health Initiative, postmenopausal women who
lost more than 5% of their baseline weight within 3 years of follow-up had 65%
higher rate of hip fractures as compared with women with stable weight (<5%
change). This confirms that body weight is positively associated with bone
health [74].
Frail women are at increased risk of recurrent falls compared with non-frail
women [75], and most hip fractures are secondary to falls [76]. A lower muscle
mass may lead to accidents or falls [77], with secondary fractures, but falls could
also be a confounding factor, indicative of poor general health [78]. Conversely,
higher fat mass might be protective during falls by fat cushioning [69].

14.6 Diagnosis of Metabolic Bone Disease Applied

to the Elderly

14.6.1 Radiography

Findings suggestive of osteoporosis can be frequently found on radiographs. The

main radiographic features of osteoporosis consist of increased bone radiolucency,
cortical thinning, and changes in the trabecular pattern [79]. The first sign results
from the decline in BMC and deterioration of the trabecular microarchitecture; this
feature is detectable only in the advanced stages of the disease, when the amount of
bone loss reaches at least 30% [80] (Fig. 14.1).
Cortical thinning results from the reabsorption of the periosteal, intracortical,
and endosteal layers. When this happens in the vertebral bodies concomitantly to
the increase in bone radiolucency, the vertebrae acquire a “picture frame” appear-
ance, also known as “ghost vertebra” [80] (Fig. 14.2). In the early stages of osteo-
porosis, this cortical thinning appears as scalloping in the inner margin of the cortex
(endosteal scalloping).
The alteration in trabecular pattern happens because trabeculae offer a greater
surface area for resorption processes and respond faster to metabolic changes than
cortical bone. Trabeculae are more abundant in the axial skeleton and at the ends of
the long bones. Secondary trabeculae, which are not primarily involved in weight
bearing function, are lost first, while the primary trabeculae become more promi-
nent and disappear at later stages. Using this predictable sequence of resorptive
processes, some authors developed semiquantitative indexes for the diagnosis and
grading of osteoporosis. The most widely used are those proposed by Singh et al.,
for the proximal femur, and Jhamaria et al., for the calcaneus [81–83]. These indexes
14 Metabolic Bone Disease in Geriatric Patients 377

Fig. 14.2 Multiple vertebral insufficiency fractures in the thoracolumbar transition, with different
morphology and severity. Based on Genant’s method vertebral deformities are graded according to
shape and severity. Cortical thinning results from the reabsorption of the periosteal, intracortical,
and endosteal layers. When this happens in the vertebral bodies concomitantly to the increase in
bone radiolucency, the vertebrae acquire a “picture frame” appearance, also known as “ghost
vertebra”

have a great inter-observer variation and are dependent on the quality of radiographs
and superimposition of soft tissues.
Radiographic absorptiometry (RA) (method comparing densities) and metacar-
pal radiogrammetry (evaluation of cortical changes—ratios using radiographs of
metacarpals) were developed from radiography for quantitative purposes.
Metacarpal radiogrammetry has evolved into digital X-ray radiogrammetry (DXR),
in which automated measurements obtained from three metacarpal bones (instead
of one in conventional radiogrammetry) provide more accuracy and precision,
through the calculation of a “bone volume per projected area” (VPA) from which
BMD is derived via a geometrical operation [84]. A significant correlation exists
between DXR-derived BMD (DXR-BMD) at the three mid-metacarpals and DXA-­
derived BMD at the spine, total hip, and distal radius [85].
Radiographs are also important for the diagnosis of vertebral fractures. The exis-
tence of an insufficiency fracture is an indication for treatment of osteoporosis.
Several radiograph-based methods have been developed to identify and score
VFs. Quantitative morphometry (QM), the visual semiquantitative (SQ) method,
and an “algorithm-based qualitative” (ABQ) method [86] are now available, the
most commonly used being the visual SQ method proposed by Genant et al. [87].
This method has been extensively validated and according to the ISCD official posi-
tions it represents the technique of choice to characterize VFs [57, 88]. Based on
378 M. P. Aparisi Gómez et al.

Genant’s method vertebral deformities are graded according to shape and severity.
Readers are asked to estimate the percentage of height and/or area reduction semi-
quantitatively—without a direct measurement (Fig. 14.2). The deformity is classi-
fied based on the location (anterior—wedge, middle—biconcave, or posterior and
anterior loss—crush) and on severity of height loss (normal: 0, mild 20–25%: 1,
moderate 25–40%: 2, and severe >40%: 3, plus grade 0.5 for uncertain or question-
able vertebrae). A spinal fracture index can be calculated by adding the individual
vertebral body scores. This allows a quantification of the extent of deformation [57].
An important remark about radiographs is that they represent an opportunistic
method to diagnose vertebral fractures. Fractures can be incidentally found in a
number of methods and examinations performed for other clinical purposes (e.g.
chest or abdominal radiographs) [89–91].
These fractures are currently underreported by radiologists, probably because
the main focus is set on evaluating different pathology [92]. Lastly, vertebral frac-
tures can occur as pathological fractures in the context of malignancy. In some cases
radiographs will be able to give enough information to provide unsuspected
diagnoses.
Artificial Intelligence applied to imaging is an evolving field and will be funda-
mental for this task [93].

14.6.2 Dual Energy X-ray Absorptiometry (DXA)

Dual energy X-ray absorptiometry (DXA) represents the most widely used tech-
nique for the assessment of BMD, thanks to its availability, the very low radiation
dose, and its low cost. It represents the standard for diagnosis and monitoring of
osteoporosis and conditions involving low bone mass. It is normally the first clinical
imaging tool used to diagnose osteoporosis.
DXA is based on the use of two X-ray beams of different energy. The ratio
between the degree of attenuation of the lower energy and the higher energy beam
is the “R value” and is specific for each tissue. From the R value, using complex
algorithms, it is possible to obtain the amount of BMC in pixels containing bone.
BMD is then calculated as the ratio BMC/area (in g/cm2) [79]. The DXA measure-
ment of BMD is an areal measurement [areal-BMD (a-BMD)], as opposed to a true
“density” (per volume).
BMD is expressed in terms of standard deviation (SD) comparing individual
BMD measurement to a reference range obtained from a population of healthy
young adults (T-score) and from an age-matched population of the same gender and
ethnic group (Z-score). In postmenopausal women and in men older than 50, osteo-
porosis is defined by a T-score ≤−2.5 SD at the lumbar spine (from L1 to L4),
femoral neck, or total hip [68]; BMD ≥ −1 SD is considered normal, while BMD in
the range between −1 and −2.5 SD is in the range of osteopenia (Fig. 14.3). BMD
measured by DXA accounts only for 60–70% of variation in bone strength (other
factors such as bone architecture are also contributory) and the majority of
14 Metabolic Bone Disease in Geriatric Patients 379

Fig. 14.3 DXA, lumbar spine. Woman, 73 years old, 67 kg. T-score is within the normal range
(above −1 SD)

osteoporotic fractures occur in people whose BMD is in the non-osteoporotic range

[94]. DXA performed at the forearm (focused on the distal one-third of the radius—
or the 33% distal radius—of the non-dominant forearm for diagnosis) is chosen
when the femur and/or spine cannot be accurately assessed (e.g. previous fractures,
surgery, dysplasia, severe osteoarthritis, etc.) in patients with hyperparathyroidism
and very obese patients (over the weight limit for DXA table) (Figs. 14.4 and 14.5).
Quality assurance and cross-calibration of DXA are paramount [95].
Trabecular bone score (TBS) is a gray-scale textural analysis technique which
gives extra information on bone microstructure and strength. TBS can be obtained
from a previously acquired lumbar spine DXA scan (same regions of interest, ROIs)
(Fig. 14.6). The major advantages of TBS are simplicity and low cost [96]. A dedi-
cated software is used to measure the level of variation among pixels in gray scale
within the 2D DXA image and differentiate between bone structures with similar
areal-BMD (a-BMD) but different bone microstructures [97] (Fig. 14.7).
TBS does not directly assess bone microarchitecture, but its results have been
associated with vertebral, hip, and major osteoporotic fracture risk in postmeno-
pausal women and with hip and major osteoporotic fracture risk in men aged over
50 [98, 99]. TBS gives lower values in postmenopausal women and in men with
previous fragility fractures than their nonfractured counterparts. TBS results are
lower in women who have sustained a fragility fracture but in whom DXA does not
indicate osteoporosis or even osteopenia [100] (Fig. 14.8).
380 M. P. Aparisi Gómez et al.

Fig. 14.4 DXA of the forearm. Typically, when a central site, lumbar spine and/or proximal fem-
ora, cannot be reliably assessed in patients investigated for osteoporosis, and in specific clinical
scenarios, the forearm is scanned

Other non-BMD measures from DXA scans focused on hip geometry measures,
including hip structural analysis, hip axis length (HAL), and neck-shaft angle, can
be performed, with limited value in clinical practice. HAL derived from DXA is
associated with hip fracture risk in postmenopausal women [101].
DXA and conventional radiography are the techniques of choice for the detection
of vertebral fractures [57] (Fig. 14.9). This is because of the possibility to perform
panoramic views, the lower radiation exposure, the timing (the patient can be
scanned for both BMD and VFs in the same session), the integrated morphometric
tool advantages of DXA, and the spatial resolution and better qualitative assessment
advantage of radiography. Quantitative morphometry as a scoring method remains
a useful tool in specific settings [102].
Lateral spine imaging with standard radiography or densitometric VFA is indi-
cated when T-score is <−1.0 and of one or more of the following is present: Women
age ≥70 years or men ≥ age 80 years; historical height loss >4 cm (>1.5 in.); self-­
reported but undocumented prior vertebral fracture; glucocorticoid therapy equiva-
lent to ≥5 mg of prednisone or equivalent per day for ≥3 months [ISCD 2019
guidelines].

14.6.3 Quantitative Ultrasound (QUS)

QUS is based on the interaction and the propagation of ultrasounds (mechanical

waves) through cortical and trabecular bone. Parameters on QUS reflect the struc-
tural anisotropy of bone, allowing inference of its mechanical properties [103].
14 Metabolic Bone Disease in Geriatric Patients 381

Fig. 14.5 A 71 years old female patient presented with multiple vertebral fractures (including
more than two levels at L1-L4) (a), previous fractures and surgical fixation at both proximal
femurs, and post-traumatic changes at the non-dominant forearm. The site for BMD analysis was
the dominant wrist, which confirmed a status of osteoporosis, with a T-score = −3.5 SD (b)

QUS is a non-expensive, portable technique that involves no ionizing radia-

tion. However, the reproducibility of the results, due to the diversity of available
devices and calibration, is suboptimal and can be misleading. For this reason,
according to the ISCD official positions, results from different devices cannot be
directly compared [104].
382 M. P. Aparisi Gómez et al.

Fig. 14.6 TBS analysis (explanation of software). Same patient as in Fig. 14.3. TBS shows a
normal bone structure

The main parameters assessed by QUS include speed of sound (SoS), a param-
eter closely related to bone mineralization, and broadband ultrasound attenuation
(BUA), closely related to the structural characteristics of trabecular bone [105].
There is a strong level of correlation between trabecular transmission parameters
(SoS and BUA) in the heel and BMD derived by DXA at lumbar spine and femoral
neck. Validated heel QUS devices have been demonstrated to predict fragility frac-
tures in postmenopausal women (hip, vertebral, and global fracture risk) and in men
over 65 (hip and all non-VFs), independently of central DXA BMD [104].
QUS is usually performed in the distal metaphysis of the phalanx, calcaneus,
radius, and tibia. It is important to emphasize that the only validated measurement
site in the context of osteoporosis diagnosis and management is the heel. In the
study of osteoporosis, DXA remains the method of choice in clinical practice for
therapeutic decisions, but if a DXA scan cannot be performed, pharmacologic treat-
ment can be initiated on the basis of a sufficient high fracture probability, assessed
by heel QUS (using device specific thresholds) in conjunction with clinical risk
factors (according to ISCD position) [104].
14 Metabolic Bone Disease in Geriatric Patients 383

Fig. 14.7 Woman, 71 years old, 42 kg. DXA shows very low aBMD values (T-score in the range
of osteoporosis according to WHO criteria) (a), TBS has values within the normal limits (b)
384 M. P. Aparisi Gómez et al.

Fig. 14.8 Woman, 73 years old, 92 kg. DXA shows a T-score in the normal according to WHO
criteria (a). TBS deonstrates low values - abnormal bone structure (b)
14 Metabolic Bone Disease in Geriatric Patients 385

Fig. 14.9 DXA scan for

vertebral fracture a b
assessment in an aging
patients with multiple
vertebral fractures (a) and
in a patient with a mild
vertebral deformity (b)
(fracture—red arrow) and
osteoarthritis changes

14.6.4 Computed Tomography (CT)

CT technology has evolved to offer quantitative imaging modalities to study bone

and muscle. Quantitative CT (QCT) and peripheral quantitative CT (pQCT) were
originally designed to assess bone parameters, respectively, at central and peripheral
sites. Currently they are also used for the quantification of muscle mass and fat
distribution.
The usefulness of QCT in the study of osteoporosis is related to its ability to
measure BMD in a chosen volume [volumetric-BMD (v-BMD)], with no interfer-
ence from other tissues and the possibility of studying cortical and trabecular bone
separately [106].
QCT-derived v-BMD represents a true density measure expressed in g/cm3,
instead of an areal density as measured by DXA. This avoids the DXA overestima-
tion of BMD resulting from spinal degenerative changes, vascular calcifications,
and other sclerotic lesions in the surrounding soft tissues [107] (Fig. 14.10). QCT,
compared to DXA, provides a measure of purely trabecular bone, which is more
metabolically active and may be primarily affected by metabolic bone diseases, thus
allowing for better sensitivity to detect osteoporosis [108]. QCT-derived T-scores
are however not equivalent to those obtained from DXA and therefore cannot be
used according to the WHO diagnostic classification [109]. However, the American
College of Radiology (ACR) introduced guidelines for evaluating QCT studies
386 M. P. Aparisi Gómez et al.

Fig. 14.10 DXA scan of the lumbar spine and of the non-dominant proximal femur. With aging,
osteoarthritic (OA) changes increase and particularly affect lumbar spine assessment of
BMD. Calcified ateromatosis, scoliosis, sequelae of vertebral fractures, and other conditions also
significantly impact the assessment. In the patient scanned and presented in this figure (Woman,
77 years old, 60 kg), lumbar spine shows inaccurate values due to OA changes and scoliosis (a),
while the proximal femur (b) can reliably depict a status of osteopenia (T-score −2.3 SD at the
femoral neck, not far from osteoporosis)

including diagnostic cut-off points that may be used for assigning a spine QCT
diagnostic category equivalent to the WHO guidelines (The ACR introduced guide-
lines for evaluating QCT studies [https://www.acr.org//media/ACR/Files/Practice-­
Parameters/qct.pdf]) (Fig. 14.11).
14 Metabolic Bone Disease in Geriatric Patients 387

Fig. 14.11 American

College of Radiology
guidelines for QCT studies

The region of interest for QCT is the lumbar spine. Other measurement sites
commonly include the proximal femur, forearm, and tibia [109]. In clinical applica-
tion, spine and proximal femur are analyzed using standard whole-body CT scan-
ners equipped with dedicated software for the analysis. Multiple studies have
evaluated the clinical utility of QCT in fracture prediction and in longitudinal stud-
ies: the ability of spinal trabecular BMD obtained by QCT to predict spinal fractures
in postmenopausal women is comparable to or better than that of lumbar spine
BMD obtained by DXA; sufficient evidence to support this statement in men is still
necessary [110]. Total femur trabecular BMD obtained by QCT has the capability
to predict hip fractures as well as hip BMD obtained by DXA in both menopausal
woman and older men [111].
QCT has also been extensively tested in monitoring age-, disease-, and treatment-­
related BMD changes [110, 111]. However, DXA should be favored for therapeutic
decisions and in clinical practice to limit radiation exposure, unless QCT can pro-
vide superior information [111].
Also CT offers the possibility of opportunistic screening. BMD can be poten-
tially calculated from a pre-existing acquisition in patients at increased risk of frac-
ture, without need for any additional DXA scan. However, the absence of in-scan
calibration phantom and the lack of a standardized acquisition protocol are common
problems. According to the ISCD official positions (last version 2019), the identifi-
cation of patients with high fracture risk (according to low BMD or strength mea-
sures derived by CT at the spine or proximal femur) is possible with conventional
CT scan only if machine-specific cut-off values and scanner stability have been
established [110].
Multidetector spiral CT (MDCT) of the thorax and abdomen is one of the most
useful tools for opportunistic diagnosis of vertebral fractures in postmenopausal
women. On the midline-sagittal CT plane, the central area of the vertebral body end
plate (the site where vertebral fractures appear) can be very accurately analyzed.
Axial images are not very sensitive, but coronal and sagittal reconstructions are now
widely used and these may easily demonstrate fractures. The initial localizer views
of CT (scout) are suitable for detection of incidental vertebral fractures [112]. Intra-
and inter-­observer agreement based on a semiquantitative method is fair to good.
Mild degrees of fracture and fractures located in levels T4 to T9 represent the main
sources of error [113].
388 M. P. Aparisi Gómez et al.

Several studies have stated that incidental osteoporotic fractures are underre-
ported and that sagittal CT reformations provide additional information and should
be a part of standard CT analyses, to improve detection rate [92]. Clinical studies
have demonstrated that MDCT structure measurements at the proximal femur and
spine improve differentiation between osteoporotic patients with proximal femur
fractures or spine fractures and healthy control patients [114]. Besides, it has been
proven useful in monitoring treatment with teriparatide [115]. Data obtained with
MDCT are useful for final element analysis (FEA), which has been used to study
bone strength and monitor changes after the administration of treatment. Using con-
version factors, reliable measurements can be calculated from the spine and hip
from routine abdominal and pelvic MDCT scans [116].
Dedicated pQCT scanners (peripheral scanners) are used to evaluate v-BMD and
bone microarchitecture at the distal radius and tibia. The use of high-resolution
peripheral scanners (HR-pQCT) is currently limited to research. Its use is yielding
important information on bone deterioration in secondary osteoporosis and related
bone diseases [117]. HR-pQCT can assess BMD, microstructural, and mechanical
parameters of both cortical and trabecular bone separately at the distal radius and
tibia with a very low effective dose, in a very localized field. HR-pQCT is limited to
the appendicular skeleton, but a good correlation has been proven between density
(a-BMD and v-BMD), geometry through cross-sectional area (CSA) and stiffness
parameters measured peripherally and those derived by QCT at lumbar spine and
proximal femur, the sites where the vast majority of osteoporotic fractures occur.
Using HR-pQCT at the distal radius and tibia, a relatively recent study docu-
mented that postmenopausal women with primary hyperparathyroidism (PHPT)
demonstrated thinner cortices, reduced trabecular BMD and cortical BMD in com-
parison with healthy controls; in the PHPT group, analysis of the microarchitecture
(individual trabecular segmentation) documented a large heterogeneity in the distri-
bution of the trabeculae and a depletion of plate-like trabeculae, with a lower tra-
becular plate-to-rod ratio [118].
In postmenopausal women with type 2 DM and history of fragility fractures
HR-pQCT has shown that both cortical bone porosity and pore volume are increased
at the distal radius and distal tibia [119]. The increased cortical porosity and the
impaired trabecular microarchitecture among type 2 DM patients could explain, at
least in part, the high incidence of fragility fractures, even though these patients
display a normal or even elevated BMD in DXA examination [120].

14.6.5 Magnetic Resonance Imaging (MRI)

On MRI, the cortical bone is dark (void of signal) because of the small number of
mobile protons and the very short T2 relaxation time. The trabecular bone is also
void of signal, but the surrounding bone marrow has high signal, with intensity
proportional to the amount of fatty content [106].
High-resolution MRI depicts trabecular bone density and structure in vitro and
in vivo with a high spatial resolution, however at resolutions similar to individual
14 Metabolic Bone Disease in Geriatric Patients 389

trabeculae dimension, partial volume effects may arise. MRI is time-consuming and
technically challenging. Since QCT and HR-pQCT can directly depict the trabecu-
lar network, they still appear the most suitable techniques for the investigation of
trabecular bone, but studies comparing high-resolution MRI with QCT and
HR-pQCT have documented that MRI performs equally well with trabecular bone
measurements [121].
The main clinical use of MRI is for the diagnosis of insufficiency/fragility frac-
tures, characterized by the presence of bone marrow edema, due to trabecular dis-
ruption. MRI allows us to confidently rule out malignancy as the cause for fracture
[122]. Optimal sequences are T1-weighted and water sensitive ones, such as fat
suppressed T2-weighted or short tau inversion recovery (STIR) [10].
Localizer images on MRI are a set of three-plane (axial, coronal, and sagittal),
low-resolution, and large field-of-view images that serve to plan the exact position
and angulation of slices of the projected MRI sequences. Localizers, despite their
limited quality, are able to demonstrate incidental vertebral fractures that can be fur-
ther confirmed by subsequently acquired T2-weighted sagittal images [90, 92]. MRI
features also allow discriminate between benign and malignant vertebral fractures
and for the correct identification of recent and old vertebral compression fractures.

14.7 Conclusion

In this chapter, we have summarized the current knowledge on changes in bone

metabolism occurring in the elderly and reviewed the possibilities of assessment
that each one of the imaging techniques offers for the adequate assessment of bone
mineral density in the geriatric population.
The loss of mineral contents in bone and structural changes is a major risk for
morbidity, need for institutionalization, and mortality. The most prevalent type of
fragility/insufficiency fracture is the vertebral compression fracture, but the effect
of osteoporosis on the skeleton is systemic, and there is increased risk of almost all
types of fractures.
Findings suggestive of osteoporosis can be frequently found on radiographs, but
the typical features are detectable only in the advanced stages of the disease.
Represents the most widely used technique for the assessment of BMD, thanks
to its availability, the very low radiation dose, and its low cost. It represents the
gold standard for diagnosis and monitoring of osteoporosis and conditions involv-
ing low bone mass. DXA and conventional radiography are the techniques of
choice for the detection of vertebral fractures.
The use of other techniques, such as QUS, QCT, and pQCT is currently more
limited, for different reasons.
MDCT of the thorax and abdomen is one of the most useful tools for opportunis-
tic diagnosis of vertebral fractures in postmenopausal women. Sagittal CT reforma-
tions should be a part of standard CT analyses, to improve detection rate.
The main clinical use of MRI is for the diagnosis of insufficiency/fragility frac-
tures and allows to confidently rule out malignancy as the cause for fracture.
390 M. P. Aparisi Gómez et al.

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2021;18:187. https://doi.org/10.2174/1573405617666210412142758.

AL GRAWANY
Body Composition in Geriatric Patients
15
Maria Pilar Aparisi Gómez, Francisco Aparisi,
Giuseppe Guglielmi, and Alberto Bazzocchi

15.1 Introduction

The process of aging is associated with a modification of body composition, with

notable consequence on physical abilities and health.
The study of body composition in the geriatric population is gaining momentum,
with the aim to mitigate some of the negative effects these changes have and imple-
ment existing interventions, such as exercise and diet [1].
As humans age, the lean components of the organism such as total body water,
organ mass, mineral bone, and skeletal muscle decrease, while total body fat
increases, with an associated redistribution: it becomes more abundant in the
abdominal region than in peripheral locations [2].
With age, endocrine and metabolic alterations occur, and besides, an increasingly
sedentary lifestyle generates a positive imbalance between intake and use of energy
[3, 4]. Aging is characterized by a low-grade chronic inflammatory status known as
“inflammaging” which has common features with the metabolism-induced inflam-
mation status known as “metaflammation,” mainly driven by nutrient excess [5].

M. P. Aparisi Gómez (*)

Department of Radiology, Auckland City Hospital, Auckland, New Zealand
Department of Radiology, IMSKE, Valencia, Spain
e-mail: [email protected]
F. Aparisi
Department of Radiology, Hospital Nueve de Octubre, Valencia, Spain
G. Guglielmi
Clinical and Experimental Medicine, University of Foggia, Foggia, Foggia, Italy
e-mail: [email protected]
A. Bazzocchi
Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 397
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_15
398 M. P. Aparisi Gómez et al.

The increase in body fat and the redistribution of the fat in geriatric population
have been demonstrated to be associated with risk factors for non-insulin-dependent
diabetes and cardiovascular (CV) disease [6].
The loss of mineral contents in bone and structural changes are a major risk for
morbidity, need for institutionalization, and mortality. Sarcopenia, with a decrease
in muscle mass and function, has been associated with impaired immunity and func-
tional status [7, 8].
The three tissues (fat, muscle, and bone) have a very close relationship, and
therefore analysis and evaluation should be approached in a combined way.
Several methods are available for the assessment of body composition in geriat-
ric population.
Clinical measures such as BMI, waist circumference, waist-to-hip ratio, under-
water measurement, and bioelectrical impedance (BIA) are widely used as indica-
tors of body adiposity, but growing evidence demonstrates their inaccuracy and
inability to reflect body fat distribution [9].
Imaging tools offer tremendous advantages in research that can be transferred to
clinical practice. From dual-energy X-ray absorptiometry (DXA) and ultrasound to
computed tomography and magnetic resonance, imaging tools allow a more accu-
rate estimation and characterization of body composition.
In this chapter, we aim to summarize the current knowledge on changes in body
composition occurring in the geriatric age and review the possibilities of assessment
that each one of the imaging techniques offers for their adequate measurement in
the geriatric population.
The contents of this chapter need to be taken into consideration together with the
chapter on metabolic bone disease in geriatric patients. The effects of aging on bone
are extensively reviewed in a dedicated chapter, but it is important to acknowledge
the close relationship and interrelation existing between all components.

15.2 Changes in Body Composition with Aging

Aging induces a decrease in basal metabolic rate (estimated as 5–25%) [10], and
this leads to an increase in body weight and body fat, even if there is no change to
the dietary intake. In most individuals, body fat increases gradually between the
ages of 20–25 and 65 [11].
At the same time, there is a redistribution of the adipose tissue to the abdominal
region (android distribution) and visceral organs and fat infiltration into muscle and
bone [12]. Bone marrow fatty infiltration occurs with aging [13], but also in the
context of diabetes, anorexia nervosa, and starvation [14].
The evaluation of fat as a factor in aging is challenging and made worse by the
lack of consensus in the clear cut off for obesity. In the clinical context, obesity clas-
sifications are based on BMI values, but the value of this measurement for classifica-
tion is limited [15]. The quantification of percentage of body fat can be performed
with DXA or bioimpedance analysis (BIA) with much more accuracy, but there is
still no consensus on the percentage of body fat that constitutes the cut off for obesity
15 Body Composition in Geriatric Patients 399

in men or women. The cut off of 32% was suggested recently [16, 17], with the dem-
onstration that 33–38% showed adverse influence on bone mineral density [18].
Muscle and bone tissues decrease with aging. The peak of muscle mass occurs at
approximately 30 years of age, with a gradual decrease after that. By the age of 70,
a decrease in muscle mass of 20–40% can be expected, leading to sarcopenia [19].
Dynapenia constitutes a different concept [20], consisting of loss of muscle strength
and not necessarily muscle mass.
The declines in bone mineral density and muscle mass are more marked in
women [21]. Bone mineral density declines with age, starting at about 50 years. At
the same time, there is an increase in the bone turnover rate, with increased bone
resorption, leading to bone loss [22]. In women, during the 5–7 years after meno-
pause, there is a decrease in bone mass of up to 20%. After this period, in normal
conditions, the rate slows down to 0.5–1% per year (National Osteoporosis
Foundation). For men, the rate is steady at 0.5–1% and starts later in life (National
Osteoporosis Foundation).
The concept of osteosarcopenic obesity syndrome represents a triad of deteriora-
tion of bone, muscle, and adipose tissues [16, 23]. The concept was first coined for
older women, but a recent study points out that this phenotype may exist in younger
overweight populations (18–21 years) [24]. Within this syndrome, two underlining
components have been recognized, osteopenic/osteoporotic obesity [12] and sarco-
penic obesity [16], which can exist separately.
The three tissues (fat, muscle, and bone) have a very close relationship and there-
fore evaluation needs to be done in a combined way.

15.3 Analysis of Body Composition Changes

15.3.1 Fat

With aging, there is a global increase in body fat, up to the age of 50–60 [25].
Subsequently, there is a trend of a reduction in fat mass after the age of 80 [26]. The
loss of skeletal muscle mass contributes to an increase in body fat percentage [27].
An accelerated loss of lean mass has been associated with greater body fatness in
old age [28].
The increase in body fat has an important role in the increase of pro-­inflammatory
cytokines. Adipose tissue secretes interleukin (IL)-6 and tumor necrosis factor
(TNF)-alfa [29, 30]. The relative amount of truncal fat measured with DXA corre-
lates with the levels of these markers in plasma [30].
Intraabdominal fat increases with age quantitatively, but proportionally more than
peripheral fat mass [31–33]. The increase of intraabdominal fat starts before the age
of 20 in men and women, accelerating with menopause in women. A study performed
with DXA showed the ratio of upper to lower body fat increases linearly after 20 years.
From 20 to 70, the ratio increases from 1.07 to 1.67 in men and from 0.81 to 1.21 in
women [32]. On a study using CT, the increase of intraabdominal fat at L4 increases
linearly with advancing age, even without significant changes in fat mass [31].
400 M. P. Aparisi Gómez et al.

Besides from the redistribution of body fat, another feature of the changes in
body composition with aging is the infiltration of tissues by fat. This has been
mostly determined for muscles, thanks to the use of MR. Different studies suggest
that the amount of intermuscular fat increases rapidly with age, at a yearly rate of
10% for men and 6% for women. The increase is more noticeable in people with a
global increase in body weight, but it is also seen in people who lose weight [34, 35].

15.3.1.1 Causes for the Increase of Intraabdominal Fat with Aging

The redistribution of fat could be caused by different factors, such as age itself,
hormonal changes, reduced fatty acid use, reduced physical activity, and resistance
to leptin [36]. An increase in intraabdominal fat has been linked with an increase in
most markers of cardiovascular risk, such as dyslipidemia, hypertension, and insu-
lin resistance [37].
Withdrawal of estrogens with menopause is an independent factor inducing
intraabdominal fat accumulation in women [38], corroborated by the fact that hor-
monal replacement therapy can prevent negative effects of menopause.
Changes in the production of testosterone can also cause accumulation of intraab-
dominal fat [36]. Low androgen production in men and high androgen production in
women are associated with abdominal obesity. The increased secretion of cortisol
could explain the alterations in the production of sexual hormones. Increased corti-
sol secretion is directly associated with intraabdominal fat accumulation (like in
Cushing’s syndrome).
The concept of the hypersensitivity of the hypothalamus–pituitary–adrenal
(HPA) axis was researched by Bjoerntorp et al. [36]. The HPA is highly activated in
cases of abdominal obesity, by different etiology stressors, and the consequences
are aggravated by lack of efficient control by the glucocorticoid receptors of the
central nervous system. This results in constant pulses of corticotropin-releasing
hormone, adrenocorticotropin, cortisol, and adrenal androgens.
The loss of muscle mass and decrease in physical activity are associated with
insulin resistance [39] and decreased fatty acid oxidation [40]. In resting conditions,
obese people, and type II diabetes, muscle fatty acid uptake is reduced with insulin
resistance. Fatty acid uptake was found to be inversely related to visceral fat, sug-
gesting that it is possible that the increase in intraabdominal fat could be a conse-
quence rather than a cause of the alteration of fatty acid utilization [41]. Age may be
associated with a decrease in the metabolic activity of muscle, because fatty acids
have a smaller contribution to the supply of energy in elderly people than in younger
adults [42]. The capacity of respiring tissues to oxidize fat declines with age [43].
The decrease in fat oxidation is related to a reduction in the quantity but also the
capacity of skeletal muscle to oxidize fat.
Leptin is secreted by the fatty tissue and is involved in the regulation of energy
homeostasis. The circulating leptin level mainly reflects the amount of energy stores
in adipose tissue and directs the central nervous system in regulating energy homeo-
stasis, neuroendocrine function, and metabolism [44]. Studies in identical twins that
were discordant for obesity demonstrated an increase in circulating leptin in the
15 Body Composition in Geriatric Patients 401

obese twin [45], and subsequently, different studies have demonstrated that leptin’s
effects are largely absent in obese hyperleptinemic state, probably due to resistance
or tolerance [46].

15.3.1.2 The Metabolic Consequences of the Intraabdominal

Accumulation of Fat
Several descriptive and interventional studies in the past decades demonstrated
insulin resistance is related to the increase in intraabdominal fat, as opposed to
related to aging per se [47].
Insulin sensitivity was shown to be independently and negatively correlated with
intraabdominal fat (measured as waist-to-hip ratio), which was not the case of age
or obesity, in an early study by Coon et al. [48]. In studies using MRI in overweight
patients, intraabdominal fat was seen to correlate with insulin resistance after con-
trolling for BMI [49, 50]. Studies in identical twins support these results [45].
Intervention studies in rodents such as selective surgical reduction of intraab-
dominal fat or caloric restriction [51, 52] were seen to reduce hepatic insulin resis-
tance. In human studies, in obese and type II diabetic patients, endurance training
inducing loss of intraabdominal was associated with an improvement in peripheral
insulin sensitivity [53]. Greater availability and oxidation of fatty acids are sug-
gested as the metabolic link between increased intraabdominal fat and insulin resis-
tance in several studies in type II diabetic patients [36, 54, 55].
Physical inactivity enhances intraabdominal fat accumulation, but also through
direct mechanisms, insulin resistance [11, 39].
The effect of menopause on insulin resistance is indirect, through the accumula-
tion of intraabdominal fat, but studies on the direct effects on insulin resistance are
not conclusive [47, 56].

15.3.1.3 Fat as an Endocrine Organ

It is well described that fat acts as an endocrine organ. The hormone classically
secreted by adipocytes is leptin. This has a structure that resembles the structure of
IL-6 and therefore stimulates the pro-inflammatory action of IL-6, but also IL-12
and TNF alfa [57, 58]. The levels of leptin are higher in women and increase pro-
portionally with the volume of fat mass [58]. The levels of leptin decrease progres-
sively with age, more markedly in women than in men, independently from
BMI [59].
Leptin has a local effect on bone, enhancing osteoblastogenesis and inhibiting
osteoclastogenesis, through the differentiation of marrow stem cell precursors, and
in that sense, promotes bone formation [60, 61]. Centrally, the effect of leptin can
either be positive or negative, increasing resorption through a hypothalamic–brain-
stem serotonin mediated mechanism on osteoblasts [62]. Leptin also activates pro-­
inflammatory pathways in osteoblasts, directly, contributing to bone loss [63].
Decreased serum leptin is found in frail elderly and in cachexia [64]. Obesity
leads to leptin resistance and hyperleptinemia, so cases in which there is concomi-
tant osteosarcopenic obesity may go undetected.
402 M. P. Aparisi Gómez et al.

Adiponectin is a hormone secreted by adipocytes but also by myocytes and

osteoblasts.
Circulating adiponectin is decreased in older individuals.
Some studies demonstrated that adiponectin had a negative impact on bone mass
by decreasing osteoblast proliferation [65, 66], but other studies showed that through
the same pathway, adiponectin inhibited osteoclastogenesis [67, 68].
Adiponectin also has anti-inflammatory effects, inhibiting the effects of TNF alfa
and IL-8 [69]. Hypoadiponectinemia is positively associated with visceral fat and
obesity related diseases.
The combined effects appear to favor lean mass and less fat accumulation [70].
Serum concentrations would be lower in osteosarcopenic obesity, due to increased
fat mass and decreased lean mass, but since adiponectin increases with age, the
decline may be masked.
Adipose tissue has also been seen to have an endocrine effect on muscle metabo-
lism, on an adipo-muscular axis that can modulate changes between physiologic
and pathologic situations, including, for example, obesity and inflammation, but
also aging.
An increase in loss of lean mass has been associated with an increase in fat accu-
mulation in old age, and a significantly greater quantity of lean mass is lost in weight
loss than is gained during weight gain in old men [28, 71].

15.3.1.4 Fat Mass and Its Effects on Mobility and Mortality

In the geriatric population, obesity, as defined by a BMI beyond 30 kg/m2 was
shown to be closely related to a decline in functional performance, with a 60%
increased risk of mobility limitations, potentially leading to disability [72].
Recent evidence points toward overweight status (BMI comprised between 25
and 29.9 kg/m2) also being associated with an increased risk of mobility limitations
and disability in the elderly [73–75].
Moreover, increased BMI plays a role in functional performance over time. The
Health, Aging, and Body composition study reported that in overweight or obese
adults since age 25, the risk of developing mobility limitations as old men or women
was 3 times higher compared to adults that maintained normal weight [76]. In peo-
ple that became overweight or obese during old age, the risk was only 1.7 times
higher. Weight instability has been associated with a higher risk of limitation on
daily tasks and impaired mobility in the elderly [77].
The correlation between BMI and mortality in the elderly has been described as
having “U” or “J” shaped curves. There is an increased risk of death with low BMIs
(although this can be biased by cachectic states linked to cancer, for example) and
there is also an increased mortality risk in the obese elderly. For overweight adults,
reports are conflictive [78], with a recent meta-analysis concluding overweight sta-
tus is not associated with increased mortality, whereas obesity is. Recent studies
support that a high BMI negatively affects healthy life expectancy, and is associated
with an increased risk of cancer mortality, in particular colorectal cancer [79, 80].
However, the measurement of body composition through BMI is far from accu-
rate and an increase in weight does not necessarily imply an increase in adiposity,
15 Body Composition in Geriatric Patients 403

could reflect an increase in muscle mass, for example. In this regard, other clinical
markers, with a better correlation with fat distribution, which in turn has a correla-
tion with specific traits of aging have been used.
As an example, a large waist circumference has been associated with mobility
limitation and disabilities in different studies [81, 82], with a greater association in
inactive older adults [72]. Interestingly, a longitudinal study found that modification
in waist circumference was not associated with a change in self-reported disability
and that the main predictor associated with physical decline was the reduction in
appendicular fat free mas [83].
In fact, muscle fatty infiltration on CT was associated with a higher risk of inci-
dence of mobility limitations in individuals (men and women) over 70 [84, 85].
An increased waist circumference in old adults has been seen to be a predictor of
mortality, even corrected for BMI, and this association was reported to be depen-
dent of cardiorespiratory fitness [86]. In older men, waist circumference has been
reported as a stronger predictor for mortality than BMI. In a study assessing asso-
ciations between BMI, waist circumference, and specific causes for mortality, waist
circumference was the only one to show statistically significant positive associa-
tions with death from major causes (lung cancer, chronic respiratory disease, among
others) [87].
A study using DXA to quantify central adiposity and mortality described a “J”
curve between the two [88]. In a study using CT to quantify visceral fat, the conclu-
sions were similar, with an increased risk for men over the age of 50 [89].
Finally, in the subgroup of very old adults, obesity determined by BMI appears
unrelated to mortality, so it is possible that the relationship between adiposity and
mortality may vary with age [90], but more research is needed in this field.

15.3.2 Skeletal Muscle

Sarcopenia is used to refer to the gradual loss of skeletal muscle mass and strength
that takes place with aging. It should be distinguished from cachexia, which corre-
sponds to muscle loss caused by inflammatory diseases and also from the weight
loss and wasting that happens in the context of starvation or advanced disease.
There is growing evidence that sarcopenia occurring with aging has important
consequences in old age, through its association with weakness, disability, and mor-
bidity [91].
In elderly population, the coexistence of superimposed illnesses will act as an
accelerator in the loss of muscle mass, increasing the risk of disability and death.
A unique consensus with the specific cut-off values or the most appropriate tech-
nique for the assessment of low skeletal muscle mass in old adults has not been
reached yet.
DXA has been used to explore changes in total and regional body composition,
including appendicular skeletal muscle mass of legs and arms, which is the sum of
lean mass of legs and arms.
404 M. P. Aparisi Gómez et al.

The deterioration in skeletal muscle mass in the elderly has been measured in
several studies by using CT cross-sectional area, and also whole-body MRI, as tech-
niques that provide an accurate quantification of skeletal muscle mass loss, given
they allow for precise segmentation. The yearly decline has been calculated to be
between 0.64% and 1.29% per year for old men and between 0.53% and 0.84% per
year in old women [28, 83, 91–93].
The loss of muscle mass with age and the increase in body fat put old adults at
risk of developing sarcopenic obesity.
Recent studies have used DXA to demonstrate a general decrease of lean mass at
the upper and lower limbs with age in both genders. The decrease in lean mass was
seen to an increase in fat mass. Lean mass was seen to decrease after 40 years of age
in men, particularly after 50, and after 50 years in women. Women seemed to main-
tain a more favorable lean mass in arms during aging [94].
Anthropometry was also found to not be representative of lean mass of arms in
both genders, independently of age, favoring imaging techniques for the correct
assessment of body composition of the limbs [95].

15.3.2.1 Causes for the Decrease of Muscle Mass with Aging

Pathophysiologically, sarcopenia has been attributed to a reduction in muscle fiber
number and size [96].
Type II fibers (white, fast twitch fibers) are more susceptible than type I fibers
(red, slow twitch fibers) to atrophy and loss with aging [96]. Sarcopenia is muscle
specific, with some muscles exhibiting substantial loss with age (e.g., vastus latera-
lis, rectus femoris, soleus, plantaris, gastrocnemius, extensor digitorum longus) and
others showing relative preservation (adductor longus, flexor digitorum longus as
examples).
The mechanisms of development are thought to be diverse, including selective
decline and changes in the motor-unit organization, injuries due to contraction, defi-
cit satellite-cell recruitment, increased free radicals and oxidative stress, and age
related accumulation of mitochondrial DNA mutations [96].
As causes of development of sarcopenia, the withdrawal of anabolic stimuli (sex
steroids, growth hormones, physical activity, dietary proteins, and insulin action),
prevalent in men, and the increase in catabolic activity (inflammation, production of
TNF alfa, IL-6, IL-1 beta) more prevalent in women have been considered [97].
Aging is influenced by a decay in the somatotropic axis, a concept that has been
coined as “somatopause.” Somatopause is a process that leads to many physiologi-
cal changes, resulting from DNA and other macromolecule damage [98]. The physi-
ological changes that occur in aging have been seen to be similar to those described
in cases of growth hormone deficiency (GHD) [99]. Similar to what happens in this
situation, there is an increase in total cholesterol and triglycerides with the subse-
quent increase in CV risk, a decrease in muscle mass, a decrease in exercise toler-
ance, and decreased strength.
At the same time, the increase in body fat, as seen, has an important role in the
increase of pro-inflammatory cytokines, which may contribute to the onset of
15 Body Composition in Geriatric Patients 405

muscle wasting, establishing a link between age related fat mass redistribution and
sarcopenia [30].
Sarcopenic change also involves fatty infiltration of the skeletal muscle (myoste-
atosis), which comes as a result of estrogen deficiency [100]. The pathways involved
in the development myosteatosis are two. One of them is the accumulation of intra-
cellular lipids within the myofibers (intramyocellular lipids), and the other one is
the disproportioned differentiation of the mesenchymal stem cell population into
the “adipogenic lineage,” which is responsible for the deposit of fat in between
myofibers (inter-myofiber fat). Fatty infiltration in skeletal muscle has a negative
effect on muscle health and function and results in decreased sensitivity to insu-
lin [100].
Current evidence suggests that the role of muscle changes per se is minor [101].

Vitamin D
A decreased intake of calcium, added to poor vitamin D levels and reduced renal
function during aging may result in secondary hyperparathyroidism, which leads to
sarcopenia and reduced strength [102]. Vitamin D controls together with parathy-
roid hormone (PTH) the intestinal absorption of calcium in a negative feedback loop.
Relatively recent studies have demonstrated that vitamin D deficiency is com-
mon in aging [103]. Low levels of vitamin D are therefore associated with impaired
muscle strength, leading to disability and falls, through impairment of the negative
feedback mechanism and increase in PTH levels.
PTH may have a direct effect on skeletal muscle, reducing energy production and
utilization and influencing protein metabolism [104]. PTH also increases free intra-
cellular calcium and decreases plasma phosphate, increasing calcium concentra-
tions and leading to phosphate deficiency in muscle, which alters functionality
[102]. It is hypothesized that this could be one of the pathways through which high
concentration of PTH has been significantly associated with several parameters
implicated in accidental falls and frailty [105].
One of the metabolites of vitamin D is 25-hydroxyvitamin D or calcidiol, a prod-
uct of the conversion of cholecalciferol by hydroxylases in the liver. Low concentra-
tions of calcidiol have been demonstrated to be associated with overall mortality in
older persons. At the same time, the association of high serum concentrations of
PTH and higher overall mortality and cardiovascular mortality has only been dem-
onstrated to be significant in older men, but non-significant in women. Calcidiol and
PTH can therefore be regarded as important health markers [106].

15.3.2.2 The Metabolic Consequences of the Decrease

of Muscle Mass
Sarcopenia is a public health problem, independently associated with health out-
comes and disabilities. In cases of advanced sarcopenia, weakness of the muscles is
a limiting factor hindering functional capacity and performance. In cases of milder
sarcopenia, the relationship between structure and function may be complex.
Changes in muscle strength and size in response to inactivity or resistance training
406 M. P. Aparisi Gómez et al.

are not always predictable [107, 108]. The loss of skeletal muscle mass and function
can be prevented by specific intervention strategies in the fifth decade of life [109].
Sarcopenia is associated with adverse outcomes through a general increase in
morbidity and mortality, rates of hospitalization, loss of physical ability, and loss of
independence to perform activities of daily life [110, 111].

15.3.2.3 Skeletal Muscle as an Endocrine Organ

Similarly to fat and bone, muscle acts as an endocrine organ.
Troponins, the regulatory proteins associated with the contractility of skeletal
muscle are not normally found in blood, except in cases of muscle turnover or mus-
cle damage. Skeletal muscle contraction is regulated by Ca2+ through a skeletal
muscle specific troponin, and this complex is needed for the cycles of contraction
and relaxation. The skeletal muscle is protected by layers of connective tissue, but
if the barrier is injured, components of the muscle, particularly these skeletal muscle
specific troponins get released into the bloodstream and their presence could be
indicative of sarcopenia [112, 113]. Recently, it has been demonstrated that the drop
of these troponins in serum is proportional to improvements in handgrip strength
and overall physical fitness in older adults [114].

15.3.2.4 Lean Mass and Its Effects on Mobility and Mortality

There is a number of studies which show that sarcopenia is related to a poorer func-
tional status or to a 5-year functional decline in elderly patients [115]; however,
other studies show opposite results, but this may be due to the confounding role of
excess adiposity [88]. Sarcopenia has been seen to not be associated or only weakly
associated with compromised functional capacity [116–118] and future functional
decay [74, 84]. It is the high body fat mass that strongly affects functioning in old
individuals, suggesting that the impact of an excess body fat is far more important
than a low skeletal muscle mass.
Recent cross-sectional studies have not supported either that a mixture of low
muscle mass and high body fat mass has worse outcomes regarding functional sta-
tus than high body fat mass alone. If only sarcopenia is considered, no association
with increased risk of poor functional status is found [117, 119, 120].
It has been suggested that prominent muscle mass loss (wasting) in old aging
may intensify functional limitations and disability. A study monitoring old individu-
als for 5.5 years demonstrated that the loss of appendicular mass and leg muscle
mass (assessed by DXA) correlated with a decline in disability score [83]. Another
study showed changes in the appendicular skeletal muscle mass over 5 years had a
faint and positive association with changes in physical function measurements [121].
Yet, it remains unclear if the actual decrease in skeletal muscle mass or the invol-
untary decrease of body weight could be the crucial factor inducing functional sta-
tus decline [122].
After voluntary weight loss, the loss of fat mass in the abdomen and thighs com-
pared to changes in skeletal muscle mass was the main determinant of improved
functional performance [123].
15 Body Composition in Geriatric Patients 407

Regarding mortality, it has been proven that mow muscle mass in the inferior
limbs (measured with CT or DXA) was not strongly associated with a 4.9 years mor-
tality risk in individuals aged 70–79 [124]. The In Chianti study concluded that the
calf muscle area (measured with peripheral quantitative CT) was not associated with
a 6-year mortality risk [125]. The study found no association between sarcopenic
obesity and mortality. A large study of Chinese individuals demonstrated that 5 year
mortality risk between sarcopenic and non-sarcopenic individuals was similar [121].
However, results may be contradictory, a recent 4.6 year follow-up study in a
large population (4331 subjects aged 65–93 years) demonstrated that the loss of
appendicular muscle mass (measured by DXA) was associated with an increased
mortality risk [126].

15.4 Imaging of Body Composition in the Elderly

Numerous clinical methods are in use for the assessment of body composition.
Among the anthropometric methods, BMI measurement has been used as a mea-
surement of body fatness, due to its simplicity; however, it is widely known that it
does not reflect the distribution of body fat. In fact, the analysis of BMI together
with body composition parameters by DXA reveals that groups with very similar
BMI have a different amount of fat, lean, and bone masses [9, 127]. Other clinical
methods such as waist circumference measurement, waist-hip ratio, and other tech-
niques such as underwater weighing and bioimpedance analysis are also available.
The attention of clinicians has turned into imaging methods, however. This is due
to the great advantages regarding reproducibility and accuracy in research. Imaging
methods allow to divide body mass into its components based on their different
physical properties.
Imaging methods are the choice for calibration of field methods designed to mea-
sure adipose tissue and skeletal muscle in vivo and are the only methods that allow
the measurement of internal tissues and organs [128].
Based on the information that is needed, the degree of accuracy, the safety of
assessment, time required, and cost, different imaging methods can be used, such as
DXA, ultrasound, computed tomography, and magnetic resonance. Each one has its
special advantages and limitations (Tables 15.1 and 15.2).
Currently, DXA represents the reference method for the assessment of body
composition. It is fast, involves low radiation exposure, and is unexpensive. It is also
an imaging tool widely used in research [9]. Recently, it has been used in the
NU-AGE study, carried out in five different European countries, among healthy
elderly individuals, showing that body composition characteristics are different
among the elderly in Europe and that a favorable adipose related inflammatory pro-
file is associated with a favorable profile of fat and lean mass markers in body com-
position [127].
408 M. P. Aparisi Gómez et al.

Table 15.1 Summary of imaging markers for assessment of visceral fat, adipose tissue distribu-
tion, and risk of cardiometabolic diseases
Method Parameters Uses Disadvantages
DXA Visceral adipose Positively correlated with clinical Need for advanced
tissue (VAT) and laboratory parameters segmentation tools (otherwise
associated with cardiovascular approximation to android fat)
and metabolic syndrome risk
US Visceral fat Satisfactorily correlated with Standard values have not
thickness clinical and laboratory parameters been determined, and
parameters therefore the application of
Subcutaneous fat Potential use to quantify the technique is limited
thickness intracellular fat in liver
parameters
Intracellular fat
thickness
parameters
CT Linear Excellent spatial resolution Radiation
measurements Cost
(similar to US) Complexity
Cross-sectional Quantification and adipose tissue Currently used in research
Area (CSA) distribution from different body
segments can be achieved with a
high level of accuracy
Volumetric Potential opportunistic use
estimates
MRI Cross-sectional High spatial resolution and Cost
Area (CSA) accuracy Complexity
Volumetric Potential opportunistic use Currently used in research
estimates
Skeletal muscle
fat
Bone marrow fat
Intracellular fat

Table 15.2 Summary of imaging markers for assessment of muscle mass and risk of sarcopenia
Method Parameters Uses Disadvantages
DXA Appendicular Lean mass status could be defined Definition of low lean mass
lean mass using ALMI with Z-scores obtained still has to be established and
index (ALMI) from an age, ethnicity, and validated
sex-­matched population
US Muscle Limited use in clinical practice Parameters vary with aging to a
thickness different extent in different
studies. Needs further
validation
Cross- Potential use Operator dependent
sectional Area
(CSA)
Echo intensity
Fascicle length
Pennation
angle
15 Body Composition in Geriatric Patients 409

Table 15.2 (continued)

Method Parameters Uses Disadvantages
CT Cross- Excellent spatial resolution Radiation
sectional Area Cost
(CSA) Complexity
Volumetric High level of accuracy on Currently used in research
estimates quantification of skeletal muscle
composition
Potential opportunistic use
MRI Cross- Possible to detect changes in Cost
sectional Area muscle structure due to aging and Complexity
(CSA) disease progression
Volumetric Potential opportunistic use. Currently used in research
estimates

15.4.1 Dual-Energy X-ray Absorptiometry (DXA)

DXA is a standard technique for the assessment of human BC, with a good level of
correlation between the measurements of skeletal muscle mass at lower limbs
derived by DXA and those derived by CT and MRI [129]. DXA has also been vali-
dated against post-mortem measurement of muscle, skin, and viscera [130].
DXA is based on the physical principle that X-rays of different energies undergo
different attenuation when traversing different tissues. A three compartment model
is generated by radiating the body at multiple different points (pixels) using two
different energies. The pixels that do not contain bone contain a lean mass and fat
mass ratio, and the pixels that contain bone depend on bone mineral content and a
soft tissue ratio with subsequent interpolation of fat mass and lean mass ratio, based
on pixels in vicinity to the ones with bone. In this way, fat mass (FM), non-bone
lean mass (LM), and bone mineral content (BMC) can be obtained. In pixels with-
out bone, soft tissue is further characterized as FM and non-bone LM [131]
(Fig. 15.1).
With DXA, total body, and standard regional (trunk, arms, legs, android, and
gynoid regions) body composition measures can be obtained.
As we have seen, body composition variation with age involves among others a
progressive decrease in LM and increase in FM (sarcopenia and sarcopenic obesity)
and also redistribution of FM to the abdomen. These changes can be monitored by
DXA [117]. An abdominal or android region distribution of FM has been associated
with the development of higher risk profile for cardiovascular and metabolic dis-
eases [132]. The DXA android region was designed to be as representative as pos-
sible of abdominal fat, thus to predict metabolic risk of patients.
DXA with dedicated software allows the analysis of visceral and subcutaneous
adipose tissue (VAT and SAT, respectively) in the android region (a segment of the
abdomen comprised between a lower demarcation line joining the superior limits of
the iliac crests and an upper demarcation line drawn at a level representing 20% of
the distance in between the iliac crests line and the chin). SAT can be estimated and
410 M. P. Aparisi Gómez et al.

Fig. 15.1 DXA analysis of body composition. Measurements are based on a 3-compartment
model that can be simplified into fat mass (FM—yellow), non-bone lean mass (LM—red), and
bone mineral content (BMC—white). Body masses and bone mineral density (BMD) can be
assessed on a regional or a whole-body basis

then subtracted from android total FM to obtain VAT (in grams and volume). DXA-­
assessed VAT measurement has been validated against CT in a wide range of age
(18–90 years old) and BMI (18–40 kg/m2) [133] (Fig. 15.2). Most of the risk is
related to VAT compartment, while SAT plays a controversial role. The two fat
depots are distinct in their endocrine function, with different impacts on glucose
metabolism.
DXA specific measurements of LM allow for the calculation of indexes such as
lean mass index (LMI: total LM/height2), appendicular lean mass (ALM: arms
LM + legs LM), and appendicular lean mass index (ALMI: ALM/height2) [134].
ALMI is of clinical significance, because the maintenance of appendicular skele-
tal muscle mass is critical in the preservation of mobility and functional indepen-
dence in advanced age, with subsequent impact on morbidity [135]. According to the
International Society for Clinical Densitometry (ISCD) guidelines, lean mass status
could be defined using ALMI with Z-scores obtained from a young adult, race, and
sex-matched population; however, the threshold for the definition of low LM is yet to
be set and validated [136]. In recent years, age- and sex-specific data on ALM
obtained from general population have been collected in different countries and
could be useful as a reference standard to monitor the loss of muscle mass [95].
Recent several studies in different populations have focused on collecting body
composition data as reference standards, especially in healthy people, to set tools
for comparison on groups of patients affected by different conditions. In this con-
text, postmenopausal status is part of normal aging in healthy women [137, 138].
15 Body Composition in Geriatric Patients 411

Abdominal
VAT SAT
wall

Fig. 15.2 Visceral fat assessment by DXA. DXA with dedicated software allows the analysis of
visceral and subcutaneous adipose tissue (VAT and SAT, respectively) in the android region (a seg-
ment of the abdomen comprised between a lower demarcation line joining the superior limits of
the iliac crests and an upper demarcation line drawn at a level representing 20% of the distance in
between the iliac crests line and the chin) (red area in the drawing and DXA image). SAT can be
estimated and then subtracted from android total FM to obtain VAT (in grams and volume)

The National Health and Nutrition Examination Survey (NHANES) produced

reference body composition values for adults over 60 years old [139].
DXA has the advantages of being non-invasive, quick, and safe. Radiation expo-
sure is very small (less than 1 μSv for whole-body scans), and therefore it has a high
degree of safety and makes it ideal for repeated measurements for longitudinal
assessment.
It is also substantially cheaper than CT and MRI. DXA also has low precision
errors [130, 140]. Another important advantage is that it can be used to assess
bone mass.
In the elderly, situations in which there is lack of correct hydration may impair
DXA analysis, because the hydration of the lean mass is assumed as constant and
uniform [140]. Inaccuracy can also arise from the thickness of the lean tis-
sue [130].
DXA is a projectional technique, and as such measures lean mass as opposed to
muscle mass in the body (cannot measure skeletal muscle mass specifically in
412 M. P. Aparisi Gómez et al.

non-­limb regions of the body, which means it includes other soft tissues in the mea-
surement). Despite this, the measurement of lean mass is frequently used as a proxy
to muscle mass.
DXA may underestimate total lean mass in the body depending on hydration
status (water retention in heart, liver, kidney failure) and overestimate appendicular
lean mass [140].
Individual muscles cannot be evaluated separately, and fatty infiltration cannot
be quantified with DXA, which poses a problem for the detection of sarcopenic
obesity. DXA does not give information of the quality of muscular tissue.
Additionally, different DXA machines can measure slightly different, with dif-
ferent results. Standardization is necessary and the source of a problem. Phantoms
are not anthropometric and cannot be used as reference standards. In vivo cross cali-
bration has been suggested as alternative, but is influenced by many factors, such as
ethnicity and health status, besides from age and gender, for example [141]. Ideally
also, equations to derive lean mass and standardization of local regions of interest
should be standardized across manufacturers, or cross-manufacturer algorithms
developed [142].
Another downside of DXA is not being portable, which can pose a problem
when assessing elderly population.

15.4.2 Ultrasound

The use of ultrasound has been traditionally based on the possibility it offers to
measure thickness of tissue layers. The interfaces between layers are easy to dem-
onstrate. Ultrasound measurement procedures are accurate, reproducible, and fast.
Ultrasound is a simple, low cost, real-time innocuous technique to evaluate body
composition.
Several parameters and indexes of adipose tissue thicknesses may be measured
by ultrasound and have been proved to correlate with clinical and laboratory
parameters.
However, standardization is needed: intraabdominal fat thickness, epicardial
fat thickness, and peri and para renal fat thickness show good accuracy and reli-
ability, with good correlation with CT and MRI-derived areas and volumes
[143]. Abdominal wall fat index, pre-peritoneal fat thickness, and mesenteric fat
thickness demonstrate variable accuracy and reliability in different studies,
when compared to CT [143] (Fig. 15.3). Other indexes, such as the subcutane-
ous fat thickness, showed good correlation with MR- and CT-derived areas and
minimal and maximal subcutaneous fat thickness good correlation with
CT-derived areas [143].
A study demonstrated that reproducibility and repeatability, especially for vis-
ceral fat, were more stable in fasting state and expiration [144].
The different parameters demonstrate a variable correlation with clinical and
laboratory parameters associated with cardiovascular and metabolic risks, and in
different clinical conditions, such as type 2 diabetes mellitus [143].
15 Body Composition in Geriatric Patients 413

Fig. 15.3 Linear measurements of adipose tissue on ultrasound and CT. (a) The minimal abdomi-
nal subcutaneous fat thickness (MinASFT) is the distance between the anterior surface of the linea
alba and the fat-skin barrier, obtained at a plane through the subxiphoid region. (b) Measurement
of the pre-peritoneal fat thickness is performed from the anterior surface of the peritoneum cover-
ing the liver to the posterior surface of the linea alba, at the plane through the subxiphoid region.
(c) The maximum abdominal subcutaneous fat thickness (MaxASFT) is the distance between the
anterior surface of the linea alba and the fat-skin barrier, measured at the level of the supraumbili-
cal region. (d) Most authors measure the intraabdominal fat thickness (IAFT) as the distance from
the posterior wall of the abdominal muscle to the anterior wall of the aorta in the supraumbili-
cal region

An in-depth analysis of the correlation of US-derived parameters with clinical

and laboratory parameters of cardiovascular and metabolic risk largely exceeds the
scope of this chapter. In general, some demonstrate positive correlations with coro-
nary artery stenosis score, serum total cholesterol, triglyceride, and LDL [145], and
also hypertension, microalbuminuria, retinopathy, carotid intima-medial thickness
(IMT), and fasting Insulin concentration [146]. No correlation has been generally
demonstrated with serum HDL cholesterol [145] and insulin sensitivity [147].
US can also give an insight on the intracellular fat contents, through the evalua-
tion of hepatic steatosis, associated with metabolic syndrome and laboratory param-
eters of cardiovascular disease, and the evaluation of intramuscular fat, but with
variable reliability and accuracy.
Ultrasound has been used too to assess muscle tissue [21], but its use remains
difficult to standardize and none of the operative definitions of sarcopenia includes
ultrasound in its diagnostic algorithm. US-derived measurements of muscle mass
have shown a good-to-high level of correlation with those derived from reference
methods [148].
Sanada et al. developed regression-based prediction equations to estimate total
and regional skeletal muscle mass in healthy Japanese adults using muscle thick-
ness measurements taken at nine sites and a significant and strong site-matched
correlation was found with MRI-measured muscle mass [149]. Muscle thickness,
414 M. P. Aparisi Gómez et al.

cross-sectional area (CSA), echo intensity, fascicle length, and pennation angle of
the lower limbs are the parameters most commonly evaluated by US; in pennate
muscles, the pennation angle (angle formed at the attachment site of the fibers into
deep and superficial aponeurosis) can be evaluated in static and dynamic conditions
and provides information about mechanical and contractile proprieties [150].
All these parameters are affected by aging to a different extent but need to be
further validated. The large majority of the available studies have been conducted
with small samples and in healthy patients. As a result, no validated site-specific
cut-off points for the ultrasound-based assessment of low muscle mass in aging
patients exist.

15.4.3 Computed Tomography (CT)

CT and MRI represent the gold standard to investigate body composition at organ-
tissue level. Quantification of skeletal muscle composition and adipose tissue distri-
bution from different body segments and individual muscle groups can be achieved
with a high level of accuracy using dedicated reconstruction algorithms [151].
Based on the attenuation of an X-ray beam crossing different tissues, a CT scan
can differentiate between fat and fat-free mass. Attenuation values in skeletal mus-
cle tissue may vary between 0 and 100. Low attenuation values are proportional to
the amount of fat within the muscle (normal density muscles show attenuation val-
ues in the range of 31–100 HU, while low-density muscles show attenuation values
in the range of 0–30 HU) [152].
For the assessment of fat and skeletal mass, the most frequently used parameters
are CT-derived cross-sectional area (CSA), and volumetric estimates, and they show
good correlation with cadaver studies [153]. Thickness measurements used on ultra-
sound, in the case of fat mass, can also be applied, with similar correlation with
laboratory and clinical parameters described for ultrasound.
CT has the advantage of being performed routinely for the diagnosis of different
conditions. It therefore allows an opportunistic assessment of body composition.
On an axial CT image obtained at L3, information of total, visceral, subcutane-
ous adipose fat area (and estimation of volume through algorithms) and total psoas
area and skeletal muscle index (SMI) (as an estimation) can be obtained [154]. CT
has been used to derive a predictive cardiometabolic risk, adjusted to gender and
ethnicity [155]. CT has been used to analyze the contribution of pericardial fat,
intrathoracic fat, and epicardial fat to cardiometabolic risk [156].
The specific, targeted use of CT to assess body composition is limited in clinical
practice by the high radiation dose (risk factor for development of neoplasms), high
cost, and operational complexity. On the other side, CT exams performed for other
clinical questions are an incredibly big source for body composition assessment.
Artificial intelligence (AI) techniques are increasingly being developed, which
allow the assessment of body composition from CT images, as collateral informa-
tion from examinations performed for other clinical reasons.
15 Body Composition in Geriatric Patients 415

15.4.4 Magnetic Resonance (MR)

MRI methods have been used in multiple research studies to gain insights into the
pathophysiology of metabolic diseases including obesity, metabolic syndrome, or
type 2 diabetes mellitus. MRI parameters have been correlated with metabolic con-
trol in diabetes and with diet and physical activity intervention in diabetes [157, 158].
Adipose tissue is characterized by a short T1 and long T2 relaxation time. Fat
appears as bright on T1-weighted sequences because of a high concentration of
immobile protons. Variations of this sequence may be easily applied for the quanti-
fication of SAT, VAT, bone marrow fat, and intermuscular adipose tissue (IMAT).
Currently, whole-body scans can be obtained in approximately 5 min, and these
allow for the detailed quantification of total and regional fat deposits. Whole-body
MR scanning is the most accurate and reproducible protocol to map and measure
the amount of body fat, but is obviously expensive, and significantly time consum-
ing, not manually feasible [159]. The calculation of volumes requires semiauto-
matic segmentation based on signal intensity histograms and thresholds [160].
T2-weighted imaging has been mainly used for fat quantification in the lower
extremity muscles and is not suitable for SAT and VAT determination.
As an alternative, the acquisition of the abdominal region, which allows the mea-
surement of fat depots that are usually associated with cardiometabolic risks has
been proposed [161]. Single- and multi-slice protocols have also been developed to
make analysis faster [161]. Regarding this, the L4–L5 level has been used for single-­
slice imaging, but poor prediction of visceral and subcutaneous tissue variation in a
longitudinal study assessing changes with weight loss was reported [162]. A level
close to L2–L3 has been considered as preferred by many groups [163] (Fig. 15.4).
MRI can be used quantitatively. Single-voxel 1H-based MRS has been consid-
ered as non-invasive gold standard for ectopic (organ contained) fat quantification
using PRESS (point resolved spectroscopy) or STEAM (stimulated echo acquisi-
tion mode) sequences. Water and fat signals are identified by their chemical shift

a b

Fig. 15.4 MRI areal measurement of the different fat compartments. (a) T1 FSE image through
the level of L2-L3. (b) segmentation of SAT (yellow), VAT (red), and non-adipose tissue (blue)
(the gas within bowel loops is depicted as black and the bone as white)
416 M. P. Aparisi Gómez et al.

locations along the frequency spectrum [164]. Chemical shift encoding-based

water-fat MRI allows fat quantification with high spatial resolution. This is an
advantage when compared to single-voxel MRS as the distribution of fat content
can be spatially heterogeneous, particularly in the bone marrow [165]. Both tech-
niques have excellent spatial resolution, allowing for thickness measurements as
well as for the analysis of intrinsic tissue composition (intracellular fat content).
MRI represents the gold standard for the investigation of muscle mass and qual-
ity in a research setting; however, the high cost, limited access to the equipment and
its complexity limit the use of MRI in routine clinical practice.
A key advantage of MRI is the capability to detect changes in the muscle struc-
ture occurring with aging and disease progression, which makes it ideal for longitu-
dinal studies. Abnormal edema and the progressive accumulation of adipose tissue
and fibrous connective tissue (which are non-contractile tissues) within muscles
contribute to loss of muscle strength and quality, a critical aspect of sarcopenia and
aging. Two-point Dixon-based technique and chemical shift-based water-fat separa-
tion as quantitative MRI techniques have been frequently applied to objectively
measure muscle fat content [166]. Finally, the amount of intramyocellular lipid,
which is negatively correlated to insulin sensitivity, can be quantified by spectros-
copy (H-MRS) [159].
MRI allows for quantification of muscle size (CSA, volume), but also the com-
prehensive assessment of muscle quality. An excellent level of correlation has been
demonstrated between MRI-derived CSA values (cm2) of adipose tissue-free skel-
etal muscle (ATFSM), adipose tissue surrounding muscle and adipose tissue embed
within muscle (interstitial adipose tissue), and those obtained from cadaveric stud-
ies. Good results were also observed between cadaveric and MRI volume estimates
for the same three compartments [153].
Yang et al., in a study in old population, demonstrated that a single-slice cross-­
sectional area at the level of the mid-femur can be used in clinical practice for a fast
and non-invasive diagnosis of sarcopenia [167].
Macaluso et al. documented a significantly lower amount of muscle contractile
volume and a significantly greater amount of intramuscular non-contractile tissue in
older women (mean age: 69.5 ± 2.4 years—postmenopausal bracket) in comparison
with young women (mean age: 22.8 ± 5.7 years), in both quadriceps and hamstrings
[168]. In women over 50, MRI-measured myosteatosis was reported to be positively
associated with increased fracture risk [169], and low extremity muscle fat infiltra-
tion was shown to be negatively associated with performance based measures of
physical function [170].
In old adults (both gender), the presence of myosteatosis on MRI studies has
been detected as a predictor of poor muscle and mobility functions. When compar-
ing intramuscular adipose tissue and in frail and non-frail individuals, higher fat
infiltration was detectable in older frail subjects [171].
Compared to CT, MRI has a higher sensitivity in the detection of early fat
replacement in muscles [172]. MRI is also independent of the hydration level of
fat-free mass, which constitutes a problem with DXA, with great accuracy and
15 Body Composition in Geriatric Patients 417

minimal changes detectable in longitudinal studies, but underestimation of fat mass

and overestimation of fat-free mass have also been reported [173].
The lack of a standardized assessment protocol in image analysis represents a
methodological problem, limiting comparison between the results of different
studies [174].

15.5 Conclusion

This chapter has summarized the current knowledge on changes in body composi-
tion occurring in the geriatric age. The process of aging is associated with a modifi-
cation of body composition, with notable consequence on physical abilities and
health. Aging is characterized by a low-grade chronic inflammatory status known as
“inflammaging.”
The increase in body fat and the redistribution of the fat in geriatric population
have been demonstrated to be associated with risk factors for non-insulin-dependent
diabetes and cardiovascular disease, and besides, the loss of mineral contents in
bone and structural changes are a major risk for morbidity, need for institutionaliza-
tion, and mortality. Sarcopenia, with a decrease in muscle mass and function, has
been associated with impaired immunity and functional status. The three tissues
(fat, muscle, and bone) have a very close relationship, and therefore analysis and
evaluation should be approached in a combined way.
Imaging tools offer tremendous advantages in research that can be transferred to
clinical practice. From dual-energy X-ray absorptiometry (DXA) and ultrasound to
computed tomography and magnetic resonance, imaging tools allow a more accu-
rate estimation and characterization of body composition.
The accurate analysis of body composition in the geriatric population offers the
possibility to mitigate some of the negative effects aging has, with the potential to
implement existing interventions, such as exercise and diet, and develop new ways
to promote healthy aging in the future.

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Myeloid and Lymphoid Disorders
in Geriatric Patients 16
Patrizia Toia, Massimo Galia, Giuseppe Filorizzo,
Ludovico La Grutta, Federico Midiri, Pierpaolo Alongi,
Emanuele Grassedonio, and Massimo Midiri

16.1 Introduction

Hematological malignancies (HMs) are a type of blood cancer with a large variety
of incidence, etiology, prognosis, and survival.
HMs are the fourth most frequent type of cancer in the world with a high impact
on elderly patients, resulting in considerable morbidity and mortality. Half of all
HMs are diagnosed in patients 65 years of age and older, and this group accounts for
70% of cancer fatalities [1].
An increase in total cancer incidence among older adults is expected [1, 2].
Population aging will have a significant impact on the prevalence of HMs. The
prognosis for older patients with HMs varies widely, depending on personal fea-
tures and treatment options [1].
Aging is a complicated and multifaceted process influenced by both hereditary
and environmental factors; older people are more susceptible to infections, and

P. Toia · M. Galia (*) · G. Filorizzo · F. Midiri · E. Grassedonio · M. Midiri

Department of Biomedicine, Neuroscience and Advanced Diagnostic (BiND), AOUP Paolo
Giaccone, University of Palermo, Palermo, Italy
e-mail: [email protected]; [email protected]; [email protected]
L. La Grutta
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and
Medical Specialities (ProMISE), AOUP Giaccone, University of Palermo, Palermo, Italy
e-mail: [email protected]
P. Alongi
Nuclear Medicine Unit, Fondazione Istituto G. Giglio, Palermo, Italy

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 427
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_16
428 T. Patrizia et al.

functions of several organs are already compromised by chronic diseases. The

hematopoietic stem cells (HSCs) are not immune to the aging process, and genetic
and epigenetic damage to the HSCs contributes to the onset of malignant hemopa-
thies in older patients [3].
The World Health Organization (WHO) classification divides hematopoietic
neoplasms into three types based on their lineage (myeloid, lymphoid, and histio-
cytic/dendritic) and distinguishes neoplasms composed of precursor cells from
those composed of functionally mature ones [4, 5].
In geriatric oncological patients, it is mandatory to evaluate the level of frailty for
the best treatment choice.
Frailty is a biological condition caused by aging, comorbidities, and diseases; it
is a dynamic state that necessitates a multimodal approach in everyday practice [6]
which includes diagnostic imaging evaluation.
Indications and clinical applications of conventional radiography, computed
tomography (CT), positron emission tomography/CT (PET/CT), and magnetic res-
onance imaging (MRI) are all different.
The application of standardized diagnostic criteria is critical for accurate treat-
ment decisions [7].
The aim of the chapter is to describe radiological findings of the main myeloid
and lymphoid disorders with special regard to geriatric patients.

16.2 Myeloid Disorders

16.2.1 Myeloproliferative Neoplasms (MPNs)

Polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis

(PMF), and chronic myeloid leukemia (CML) are defined as abnormalities in hema-
topoietic stem cells that lead to clonal proliferation of myeloid lineage cell types [8].
Recognizing the radiologic signs and consequences of myeloid disorders is cru-
cial in the treatment of these hematologic cancers.
As above discussed, some authors suggest that the level of frailty in older patients
should be measured to choose the best therapy strategy [9].
Regarding the diagnosis, a significant number of patients with MPNs are detected
after undergoing a full blood count and/or peripheral blood film for another cause,
as an incidental finding.
Thrombosis, hemorrhage, splenomegaly, and extramedullary hematopoiesis can
be associated with MPN. Furthermore, similar conditions, such as splanchnic
thrombosis, may occur in the absence of a prior MPN diagnosis or a blood count
anomaly, although molecular testing can detect a JAK2 mutation and hence an
underlying MPN.
Radiologists should be conversant with these diseases to have more possibilities
to diagnose and to suspect occult MPN. The ability to acknowledge the different
accompanying radiological abnormalities, as well as the probability of an underlying
MPN in the setting of atypical thrombotic episodes, can lead to an early diagnosis [8].
16 Myeloid and Lymphoid Disorders in Geriatric Patients 429

16.2.2 Imaging Findings

The limited literature about imaging features of these disorders may result in under-­
diagnosis; however there are some imaging findings related to complications of
MPN, like thrombotic disease, marrow fibrosis, and extramedullary hematopoiesis
(EMH). Although there are no guidelines on the importance of imaging in disease
monitoring, radiologists must be aware of the most common imaging findings.

16.2.2.1 Skeletal Findings

Marrow infiltration is one of the most common findings, but cortical bone altera-
tions can also be encountered.
Osteosclerosis is commonly found in PMF on plain radiographs.
The bone marrow appears replaced by an unusually low T1 signal instead of a
high T1 signal on MRI. Also bone scintigraphy can help in the diagnosis with an
elevated skeletal uptake compared to the kidneys in case of marrow infiltration [10].

16.2.2.2 Solid Lesions

Extramedullary hematopoiesis is one of the most commonly observed solid lesions.
Extra-marrow development of new blood components most typically occurs in
the spleen and liver, followed by paravertebral regions [10, 11], but it can affect any
tissue or organ, so radiologists may be aware of patient’s medical history [12].
EMH of the liver and spleen can determine hepatosplenomegaly leading to
symptoms associated with mass effect, such as early satiety, abdominal pain, and
dyspnea in severe cases. Although focal hepatic masses have been described, EMH
involving the spleen and/or liver most usually results in organomegaly without dis-
tinct masses on imaging.
Paraspinal masses especially in the thorax are usually bilateral and well confined.
CT appearance of EMH is determined by hematopoietic activity within the
masses, appearing as solid masses at ultrasound.
On contrast-enhanced CT (CECT), active masses tend to show modest homoge-
nous enhancement, whereas older masses are more heterogeneous, with areas of fat
attenuation; MRI usually show heterogeneous signal with fat tissue compo-
nents [12].

16.2.2.3 Thrombosis
Thrombosis is a common complication of MPNs that is often detected on imaging.
ET and PV both increase the risk of thrombotic events, which can manifest in a
variety of ways. Arterial thrombi, Budd-Chiari syndrome (BCS), and portal vein
thrombosis can all impair splanchnic circulation [13, 14].
Budd-Chiari syndrome describes the clinical signs of hepatic venous outflow
obstruction, which can occur anywhere between the hepatic veins and the cavoatrial
junction.
BCS is a problem in MPN patients. Intraluminal venous obstruction, such as
venous thrombosis, causes primary BCS, whereas extraluminal venous obstruction,
such as that caused by extrinsic compression, causes secondary BCS. The sharpness
430 T. Patrizia et al.

of the thrombus, as well as the degree of venous blockage, influences imaging

findings.
The study of choice for the initial evaluation of BCS is ultrasound with Doppler
followed by contrast-enhanced CT.
Because the caudate lobe has its own venous drainage system, compensatory
caudate lobe hypertrophy can occur in up to 75% of BCS cases, causing inferior
vena cava (IVC) compression in acute situations.
In chronic stages of BCS, portal hypertension and pulmonary embolism can be
detected. The liver will seem nodular, with comma-shaped intrahepatic collateral
veins visible.
Well-perfused parenchyma tends to compensate for poorly perfused areas, result-
ing in nodular hyperplasia; because these well-perfused nodular areas, known as
large regenerative nodules, show homogenous enhancement on CECT, they are
referred to as large regenerative nodules.
Magnetic resonance imaging in acute BCS often demonstrates increased
T2-weighted signal intensity in the peripheral part of the liver, comparable to CT
findings. The caudate lobe shows normal or increased enhancement after gado-
linium administration, but the liver’s periphery shows decreased enhance-
ment [8].
The imaging study of choice for detecting portal vein thrombosis (PVT) is ultra-
sound with Doppler. On ultrasound, a thrombus usually appears as an intraluminal
echogenic lesion, albeit a newly formed thrombus may seem hypoechoic or
anechoic, with no flow at Doppler imaging or flow around a thrombus that partially
obstructs the vein.
Venous thrombus usually appears isodense or hyperdense to surrounding tissue
on unenhanced CT, but as an intraluminal filling defect on contrast-enhanced CT;
collateral veins and dilatation of the thrombosed venous segment are two indirect
CT signs.
When compared to normal hepatic parenchyma, the parenchyma of the hepatic
segment supplied by thrombosed vessels appears hypodense on CT.
MRI helps to differentiate acute from chronic thrombosis [8].

16.3 Lymphoid Disorders

B- or T-cell lymphoma, hairy cell leukemia, prolymphocytic leukemia, natural killer

cell big granular lymphocytic leukemia, myeloma, and plasmacytoma are few of the
lymphocytic illnesses that can be caused by disorders of lymphoid progenitors.
Hodgkin lymphoma is also caused by a neoplastic B cell with severely altered
immunoglobulin genes that are no longer produced as proteins [7].
Between lymphoid disorders, chronic lymphocytic leukemia (CLL) is a hemato-
logical cancer characterized by the proliferation of largely mature but aberrant leu-
kocytes and often affects adults about 65–70 years of age (Fig. 16.1). Splenomegaly,
hepatomegaly, and lymphadenopathy are some of the symptoms that might be seen
16 Myeloid and Lymphoid Disorders in Geriatric Patients 431

a b c

Fig. 16.1 Postcontrast CT axial images in chronic lymphocytic leukemia. (a–c) show multiple
abdominal pathological lymph nodes

on imaging, but they are not specific to the condition, instead lymphomas are char-
acterized by many typical radiological features [15].

16.3.1 Lymphomas

Lymphomas can be unifocal, multifocal, or diffuse, impact solitary lymph nodes or

any organ system and show a variety of imaging presentations at nearly every site.
Following the establishment of a histological diagnosis, the imaging-based first
staging will impact the treatment options and prognosis.

16.3.1.1 Chest X-Ray (CXR)

CXR plays a limited role in the diagnosis of lymphoma since it is not accurate in the
measurement of maximal transverse mass diameter, including nearby normal medi-
astinal structures, which cannot be distinguished from the tumor mass.
The presence of bulky mediastinal infiltration is a known negative prognosticator
in Hodgkin’s disease [16–21], initially documented in patients receiving only radio-
therapy [16, 20]; treatment advancements with dual modality therapy diminished
the importance of the present concept of “bulky disease”.
Because of its great concordance with CT, a chest X-ray is not necessary to
determine mass [22].
Figure 16.2 shows an example of patients with lymphoma reported by conven-
tional radiography.

16.3.1.2 CT
Computed tomography plays a crucial role in lymphoma imaging.
Normal lymph nodes have an elongated shape and a fatty hilum. Lymph nodes
infiltrated by lymphoma cells are frequently visualized incidentally or during a tar-
geted ultrasonography examination.
At ultrasound, pathologic lymph nodes are often rounded, with a hypoechoic,
pseudocystic appearance caused by the replacement of the node with lymphoma-
tous tissue.
432 T. Patrizia et al.

Fig. 16.2 A 76-year-old

woman with thoracic
lymphoma. Chest X-ray
shows pleural opacification
of the lower right field and
matting of the right lower
paraesophageal region with
sharp margins

Fig. 16.3 Non-contrast

CT scan of a 80-year-old
woman with thoracic
non-Hodgkin’s lymphoma.
Presence of multiple
enlarged lymph nodes in
about all mediastinal sites

At computed tomography, involved lymph nodes are often larger and of homo-
geneous density.
The location and subtype of lymphoma determine the imaging features.
Nodal lymphoma is a type of lymphoma affecting only lymph nodes. Extranodal
lymphoma refers to lymphoma that has spread to other tissues. Primary extranodal
lymphoma is a type of lymphoma that affects only one organ, though it can affect
many organs.
Lymphoma can affect many sites at the thoracic level (Fig. 16.3).
Pulmonary lymphoma might present as pulmonary masses or extranodal expan-
sion of thoracic nodal masses and is usually diffuse large B-cell lymphoma or
16 Myeloid and Lymphoid Disorders in Geriatric Patients 433

a b

Fig. 16.4 CT of a 84-year-old man with lymphoma of the left breast in external quadrants (non-
contrast acquisition in a and portal venous phase in b)

marginal zone lymphoma developing from bronchial lymphoid tissue, both are
uncommon. Multiple ill-defined solid or ground glass nodules or masses, consolida-
tion with air bronchograms, and interlobular septal thickening are all common CT
findings in pulmonary lymphoma [23].
Lymphoma can also be found in the breast (Fig. 16.4).
Lymphoma of the abdominal solid organs typically appears on CT scans as solid
masses enhancing at contrast-enhanced CT [24].
Diffuse organ involvement is also conceivable, typically in the liver and spleen,
resulting in organomegaly and different CT attenuation [25].
Most occurrences of splenic involvement in lymphoma are caused by diffuse
large B-cell lymphoma, Hodgkin lymphoma [26], or indolent B-cell lymphomas.
Splenomegaly is the most common imaging sign, but a normal spleen does not rule
out lymphoma involvement.
In the liver, periportal infiltration has been reported in association with hepatic
masses or porto-caval adenopathy. Pancreatic lymphoma is possible even if uncom-
mon, furthermore it may be encased by peripancreatic adenopathy [27].
Renal involvement can manifest as diffuse enlargement or focal renal masses on
imaging.
Gastrointestinal tract lymphoma is frequent in non-Hodgkin lymphoma with dif-
ferent CT scan appearance. Stomach is the most usually affected organ, followed by
small bowel and colon.
Small bowel lymphoma shows a prevalence in the terminal ileum, due to the
enormous proportion of lymphoid tissue at this region. Findings on CT imaging
include localized or multifocal intestinal wall or fold thickening, polyps, ulcers, and
aneurysmal dilatation [27].
Some examples are shown in Figs. 16.5 and 16.6.
Diffuse large B-cell lymphoma or follicular lymphoma are the most common
types of primary lymphoma of the bone. The CT appearance of osseous lymphoma
varies; isolated lesions are often lytic, but they can also be sclerotic, as seen in a
classic “ivory vertebra,” or they might have a mixed lytic/sclerotic appearance [27].
434 T. Patrizia et al.

a b

Fig. 16.5 Post-contrast CT of a 76-year-old man with lymphoma involving ileum (axial image in
a and coronal multiplanar reconstruction in b). In the mesenteric fat a mass with inhomogeneous
density due to the presence of peripheral tissue quota and central colliquate component is observed,
with hydro-air level

Fig. 16.6 Coronal

multiplanar reconstruction
of post-contrast CT
acquisition in a 76-year-­
old-man with abdominal
lymphoma characterized
by multiple confluent
lymphadenopathies in
retroperitoneal space and
in mesenteric fat,
abdominal effusion is
associated

16.3.2 Lymphoma Staging: Lugano Classification

The Lugano classification is a lymphoma staging system that applies to both non-­
Hodgkin and Hodgkin lymphoma. Presently, it is the most used staging system and
provides criteria for therapy response determined by PET/CT or CT alone.
16 Myeloid and Lymphoid Disorders in Geriatric Patients 435

A universally accepted and reproducible staging system is essential for the stan-
dardized management of patients with malignant lymphomas, in fact clinical staging
plays a larger role in the selection of patients’ treatment than any other clinical factor,
and clinical stage is one of the factors that can be used to predict disease prognosis.
A shared classification also allows a clear response evaluation, guiding therapies.
In this staging system, 18F-fluorodeoxyglucose (18F-FDG) PET/CT has been fully
integrated into the staging and response assessment of FDG-avid lymphoma. CT should
still be used to stage lymphomas with low or variable FDG uptake. Although 18F-FDG
PET/CT is strongly recommended for staging FDG-avid lymphomas, a diagnostic con-
trast-enhanced CT examination should still be included at initial staging for optimal ana-
tomic assessment [28].
CT identifies four categories: (1) complete radiologic response, all lymph nodes
less than or equal to 1.5 cm in longest diameter, and disappearance of all lymphoma
CT findings; (2) partial remission, 50% or greater reduction in disease burden; (3)
stable disease, less than 50% reduction in disease burden; and (4) progressive dis-
ease, new or increased adenopathy or new extranodal lymphoma.
Response assessment with 18F-FDG PET/CT is based on metabolic activity,
indicated by FDG uptake. The International Work Group criteria for reviewing PET
scans were based on visual interpretation and intended for end-of-treatment evalua-
tion, using mediastinal blood pool as the comparator [29].
The Deauville 5-point scale is used by the Lugano classification for documenting
response by 18F-FDG PET/CT ranging from no uptake or residual uptake to signifi-
cantly increased uptake or any new lesion.
Table 16.1 summarizes the Lugano criteria according to CT and 18F-FDG PET/
CT [29].
Recent evidences suggest that CT examination may be useful in patients with HL
who have a favorable interim or post-treatment PET-CT, with a smaller tumor mass
corresponding to a better result [30, 31]. Response evaluation based on CT is

Table 16.1 Lugano criteria

Response
Method Complete response Partial response No response Progressive disease
CT Nodal sites less 50% or greater Less than 50% New or increased
than or equal to reduction in disease reduction in adenopathy
1.5 cm burden disease burden
Complete New extranodal
disappearance of lymphoma
radiological
findings
18F-FDG Score* of 1, 2, 3 in Score* of 4 or 5 Score* of 4 or 5 Score* of 4 or 5 in
PET/CT nodal or extranodal with reduced uptake with no evident any lesion with an
sites and residual masses change in FDG increase in intensity
of any size uptake of uptake
New FDG-avid foci
consistent with
lymphoma
CT computed tomography, 18F-FDG PET/CT fluorodeoxyglucose-positron emission tomogra-
phy/computed tomography
Score* 1–5: according to Deauville 5-point scale
436 T. Patrizia et al.

favorite for histologies with low or variable FDG avidity, as well as in regions where
PET-CT is not available [31].
Other recommendations are included in the Lugano classification.
Particularly, although 18F-FDG PET/CT is widely accepted as the gold standard
for FDG-avid lymphomas, the Lugano classification recognizes the relevance of CT
for anatomic assessment, recommending contrast-enhanced CT for initial staging
and radiation therapy planning.
At the time of baseline staging, the tumor burden will be estimated. Up to six
lymphoma nodes, nodal complexes, or other lymphoma deposits are selected. The
lesions picked must be able to be measured accurately in two dimensions.
Although the Lugano classification considers detectable an adenopathy with longest
nodal diameter of more than 1.5 cm, radiologists must be aware that a lymph node
smaller than 1.0 cm with avid FDG uptake could be connected with lymphoma [29].
Splenomegaly is defined when spleen is >13 cm.
Changes in metabolic activity, expressed by SUV, can be used to quantify
response on 18F-FDG PET/CT scans. The highest SUV in any lesion on the base-
line and follow-up scan is usually measured.
Furthermore, radiologists must be aware that CT and 18F-FDG PET/CT findings
may be discordant, as in case of a significant reduction in tumor burden at CT and
increased SUV at 18F-FDG PET/CT [7].
In conclusion, the Lugano classification is used as a unified guideline for all cli-
nicians involved in lymphoma diagnosis and care because it reflects a consensus
statement of clinical experts in lymphoma. Therefore, radiologists and nuclear med-
icine specialists have a better chance of guiding clinical management based on
imaging findings thanks to these criteria [7].
Figures 16.7 and 16.8 show an example of an 18F-FDG PET/CT performed in an
old patient with a diffuse large B-cell NHL.

a b

c d

Fig. 16.7 Maximum intensity projection (MIP) representation of 18F-FDG PET (a); axial section
of PET images corrected for attenuation (b); axial section of low-dose CT used for attenuation
correction of PET images (c); axial section hybrid PET/CT images showing multiple retroperito-
neal and mesenteric pathological lymph nodes and diffuse pathological metabolic activity of the
lower pole of the spleen (d)
16 Myeloid and Lymphoid Disorders in Geriatric Patients 437

a b c

d e f

Fig. 16.8 Coronal and sagittal section of low-dose CT used for correction attenuation (a, d);
Coronal and sagittal section hybrid PET/CT images showing multiple supra and subdiaphragmatic
pathological lymph nodes, splenic and bone disease with high metabolic activity (b, e); coronal
and sagittal sections of PET images corrected for attenuation (c, f)

16.3.2.1 Whole-Body Magnetic Resonance Imaging (WB-MRI)

WB-MRI, as a radiation-free alternative to standard imaging procedures, has been
prompted by advancements in MRI technology and concerns about an increased
cancer risk in lymphoma patients due to radiation exposure associated with imaging
examinations.
There is no unanimity on the ideal approach about WB-MRI in lymphoma.
Unenhanced T1- and T2-weighted, short tau inversion recovery, and diffusion-­
weighted imaging (DWI) sequences have all been proposed and used in prior
studies [32, 33].
438 T. Patrizia et al.

The functional assessment is based on DWI, which involves the study of random
Brownian motion of water molecules in biological tissues, as measured by the
apparent diffusion coefficient (ADC) [34].
Lymphoma is characterized by increased cellularity and an elevated nuclear-to-­
cytoplasm ratio, resulting in restricted water molecule transport compared to normal
tissues, high signal intensity on DWI, and low ADC values [35].
In addition to standard dimension criteria, different WB-MRI criteria have been
established for the evaluation of lymph node involvement [36] such as DWI signal
greater than that of the spinal cord or muscles, high signal intensity at higher b val-
ues with restriction confirmed by low ADC or in the presence of central necrosis,
regardless of dimension; coalesces into a large nodal mass [37].
Despite this, there are no clear established ADC values to distinguish normal
lymph nodes from pathological ones; furthermore, no consensus has been reached
about mean or minimum ADC values to use in clinical practice.
WB-MRI has also been suggested by some authors as the best imaging tool for
monitoring indolent lymphomas (i-NHLs) and aggressive lymphomas in complete
remission [38].
Due to artifacts on DWI caused by heart pulse and respiration, WB-MRI has
demonstrated some issues in evaluating tiny mediastinal and pulmonary hilar lymph
nodes, with ADC values being miscalculated [39]. Furthermore, due to the anisotro-
pic physiologically constrained pattern of diffusion of normal splenic parenchyma
on DWI, characterization of focal splenic lesions by WB-MRI can be difficult, so
DWI must be combined with standard morphologic WB-MRI images for the evalu-
ation of the spleen [40].
In lymphoma, gadolinium-based contrast agents may increase the accuracy in
identifying parenchymal lesions during WB-MRI; it appears to be especially useful
in case of high probability of extranodal localization [40, 41].
The time required for a WB-MRI depends on the MRI unit and imaging tech-
nique and might take from 30 minutes to more than an hour.
The entire procedure takes less time than 18F-FDG PET/CT [42, 43].
WB-MRI, 18F-FDG PET/CT, and CT all have a high level of patient acceptance
when it comes to patient compliance. Claustrophobia, caused by the anxiety of
being in the enclosed area of a MRI machine for an extended period of time, is a
serious issue for patients undergoing WB-MRI [44].
WB-MRI can be used in HL patients as a complementary imaging modality to
replace contrast-enhanced CT in diagnostic work-up and lymphoma surveillance,
but it is unlikely to replace 18F-FDG PET/CT for HL staging and response assess-
ment at this time.
T2 signal intensity and contrast enhancement of lymphomatous lesions tend to
decrease following treatment, T2 signal reduction may be linked to fibrotic stroma
and collagen; however, immature fibrotic tissue, necrosis, or edema might cause an
increase in T2 signal, limiting its use in this setting [43].
WB-MRI has also been demonstrated to be useful in detecting certain recently
documented sequelae, such as osteonecrosis, in HL patients receiving chemother-
apy regimens that include large doses of corticosteroids.
16 Myeloid and Lymphoid Disorders in Geriatric Patients 439

In lymphoma, WB-MRI is an important diagnostic technique, appearing to be

less histology-dependent than 18F-FDG PET/CT as a functional imaging test. It
also does not necessitate radiation exposure.
According to the European Union directive, a radiation-free imaging method
should always be preferred if it gives the same diagnostic results [32].
Figures 16.9 and 16.10 show two examples of lymphomas detected by MRI.
In conclusion, each diagnostic technique has several advantages and
disadvantages.
18F-FDG PET/CT has a high reproducibility as CT, but it allows a functional and
standardized evaluation with clear SUV cut-off.
CT benefits of short acquisition time and wide availability, but it allows only a
morphologic evaluation; both 18F-FDG PET/CT and CT expose patients to ionizing
radiations.
WB-MRI has longer acquisition time and lower availability compared to CT but
is ionizing radiation free and with enormous potential expanding applications.

16.3.3 Multiple Myeloma

Multiple myeloma (MM) is a malignant hematological condition in which mono-

clonal plasma cells proliferate uncontrollably in the bone marrow.

a b c

Fig. 16.9 Axial postcontrast 3D-GRE T1-weighted fat suppressed (a), axial DWI b-value 800 s/
mm2 (b) and coronal maximum intensity projection (MIP) diffusion-weighted imaging (DWI) (c):
multiple lymph nodes increased in size with a tendency to confluence are shown, the largest in the
superior mediastinum and right axillary region

a b c

Fig. 16.10 (a–c) A 66-year-old man with non-Hodgkin’s lymphoma. Axial postcontrast 3D-GRE
T1-weighted fat-suppressed images: multiple lymph nodes increased in size are shown, in the right
axillary site; in the sub-diaphragmatic site there are multiple confluent lymph nodes in the paraca-
val, interaortocaval, and left para-aortic site
440 T. Patrizia et al.

16.3.3.1 Conventional Radiography

Conventional radiography allows the detection of bone anomalies, but current rec-
ommendations, such as those issued by the European Myeloma Network or the
European Society for Medical Oncology, are increasingly recommending new tech-
nologies over traditional radiography [45, 46].
Around 30–50% of trabecular bone must be damaged by osteolysis to be detected
in traditional skeletal X-ray. In many facilities, conventional radiography has been
replaced with whole-body CT as the primary imaging modality.

16.3.3.2 CT
Unenhanced low-dose CT is commonly used to diagnose bone involvement in MM
because of the strong intrinsic contrast of bony structures. The slightly higher radia-
tion dosage is tolerable in view of the much higher sensitivity and improved patient
comfort in the typically older patient population. CT has additional benefits, such as
enhanced fracture risk assessment and the ability to visualize extraosseous myeloma,
in addition to its excellent sensitivity [47].
Some osteolytic lesions in a patient with multiple myeloma are showed in
Figs. 16.11 and 16.12.

a b

c d

Fig. 16.11 (a–d) A 73-year-old woman with multiple myeloma. Low-dose CT scan images show
multiple and widespread bone lesions of a lytic character, affecting almost all the skeletal seg-
ments, between a few millimeters in size and 5 cm, the lesion at the level of the left ischium deter-
mines swollen appearance of the bone with thinning and interruption of the cortical profile
16 Myeloid and Lymphoid Disorders in Geriatric Patients 441

a b

c d

e f

Fig. 16.12 (a–f) A 77-year-old man with multiple myeloma. CT imaging shows multiple osteo-
lytic lesions and right pleural effusion

16.3.3.3 PET/CT
PET/CT imaging using 18F-fluorodeoxyglucose visualizes glucose hypermetabo-
lism in medullary and extramedullary myeloma; it also allows the morphological
detection of osteolysis as an additional functional component. Furthermore, PET/
CT allows prognostic statements during the initial diagnosis and treatment [48].

16.3.3.4 MRI
Because nearly half of all patients have focal lesions outside of the axial skeleton,
MRI is frequently conducted as a whole-body evaluation including the extremi-
ties [49].
442 T. Patrizia et al.

Table 16.2 Characteristics of infiltration patterns in patients with myeloma

Patterns Radiological features
Normal findings No pathological features
Pattern of focal T1w hypointense lesions with a diameter of at least 5 mm
infiltration
Pattern of homogeneous Bone marrow on unenhanced T1w image commonly more
diffuse infiltration hypointense than adjacent intervertebral disc spaces without
degenerative changes
Pattern of mixed Focal + diffuse
infiltration
“Salt and pepper” pattern Disseminated T1w hypointense lesions

A routine evaluation normally includes coronal and sagittal T1w and T2w
sequences, as well as fat-saturated T2w sequences.
On MRI, five different infiltration patterns in myeloma patients can be distin-
guished (Table 16.2), and the predictive value of MRI infiltration patterns has been
demonstrated in several studies.
A normal pattern of the bone marrow, or a “salt and pepper” pattern, was corre-
lated to an early stage of the disease and a better prognosis. Table 16.2 summarizes
the radiological features of the various patterns [50].

16.4 Conclusions

The growing expectancy of life is one of the main contributors for the increasing
number of older patients with hematologic malignancies.
The role of radiologist is to stage the disease, evaluating the level of frailty, but
also to identify possible complications and to assess therapeutic response.
Universally accepted and reproducible staging system is essential for the standard-
ized response evaluation.
Magnetic resonance is becoming even more important in clinical practice, espe-
cially in lymphoid disorders.

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The Role of Artificial Intelligence (AI)
in the Management of Geriatric Patients 17
Salvatore Claudio Fanni, Sherif Mohsen Shalaby,
and Emanuele Neri

17.1 Introduction

As of January 2020, the European Union population was estimated at about

447.3 million people; of which there is about 20.6% of population aged 65 years or
above. This is according to Eurostat which also declared an expanding population
of the older people in Europe; with an increase of 3% as compared to 10 years
ago [1].
In fact, it is expected that by the year 2100, there will be about 31.3% of people
older than 65 years [2], making old people the typical patients accessing healthcare
services within the few upcoming years [3].
The geriatric patients’ care is considered very complex due to the coexistence of
multiple morbidities, which are often associated with functional impairment and
even social withdrawal.
Since age is a well-known nonmodifiable risk factor for numerous morbidities,
an increase of their prevalence and incidence is expected, placing healthcare sys-
tems under stress. For instance, Alzheimer disease (AD) is the most common neu-
rodegenerative disease of people aged over 65 years, with an estimated prevalence
worldwide of 50 million, which should be increased by 2050 to 131.5 million [4].
Additionally, there will be an increase of the incidence of other diseases, such as
oncologic, musculoskeletal, or cardiovascular disease with devastating conse-
quences to our society in terms of costs of care, number of family caregivers, hours
of care provided, and the impact on caregivers. Also, as age is a common risk factor
between these diseases, usually they coexist in the same patient.
The complexity of multimorbidity is closely linked to the combination and syn-
ergy of different and numerous clinical, behavioral, environmental and lifestyle
variables on onset, progression, and severity of those morbidities [5].

S. C. Fanni · S. M. Shalaby · E. Neri (*)

Department of Translational Research, Academic Radiology, University of Pisa, Pisa, Italy
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 445
G. Guglielmi, M. Maas (eds.), Imaging in Geriatrics, Practical Issues in
Geriatrics, https://doi.org/10.1007/978-3-031-14877-4_17
446 S. C. Fanni et al.

The process of clinical decision-making for patients with chronic comorbidities

is more challenging due to the multiple coexisting diseases guidelines [6], which
additionally are primarily based on clinical trials from which are often excluded
people with multiple coexisting morbidities and older age [5].
The rapid demographic growth and complexity of geriatric patients’ account for
a though challenge, for which the advent of the new technologies may provide
important solutions.
Gerontechnology is a term first appeared in the 1990s based on two terms: “ger-
ontology,” which is the scientific study of geriatric population and “technology.”
Gerontechnology is concerned with the research on the application of technology
progress to the biological, psychological, social, and medical aspects of the aged
people [7]. To name a few of these technologies, telemedicine, wearable devices,
robotics, and assistive technologies were already implemented in order to meet the
needs of older people and are widely described in the literature [8].
In this chapter, we will discuss the diverse applications and tools of artificial
intelligence (AI) in the management of geriatric patients. AI is an area of study of
computer science, concerning with the development of computer algorithms able to
perform human-like tasks such as learning, self-correction, and even reasoning [9].
Despite it may sound far-fetched, AI is already a part of our daily life, for exam-
ple, in smartphone speech recognition, spam-filtering, and search engines [10].
A subfield of AI is machine learning (ML), which explores the study of statistical
algorithms that can learn from the available data and subsequentially make a predic-
tion [11]. A key feature of ML algorithm is the capability to autonomously adapt to
the data and improve its performance in predicting predetermined outcome [12].
Part of the broader ML field is deep learning (DL), defined as the study of artifi-
cial neural networks (ANN), implementing a cascade of many layers for feature
extraction and transformation to perform tasks such as classification or pattern anal-
ysis [13]. ANN own their name to their structure, which resemble the neural cortex:
with separate layers (the neurons) connected to each other (synapses). The ANN
most frequently described is the convolutional neural network (CNN) which is
mostly implemented in image analysis.
While traditional ML algorithms require a hand-crafted feature identification
performed by experts, a key component of DL is the capability to autonomously
identify correlated features from data during the training phase of the network.
AI could be a brilliant solution to fill the gap of human resources in geriatric
clinical care, improving patients’ outcomes and quality of life, reducing the cost and
the burden of family caregivers [14].
In fact, due to the complexity mentioned above, a multidimensional approach is
mandatory in geriatric clinical care, and AI may help to analyze the so far unex-
ploited and heterogeneous amounts of data at our disposal [15]. This mixed data
includes clinical data from electronic health records, radiological imaging, radiomics
data, genomics data, technical data from wearable devices, and many others.
Radiomics is defined as the processing of medical images into mineable data, by
extraction of thousands of hand-crafted or ML-based quantitative features from

AL GRAWANY
17 The Role of Artificial Intelligence (AI) in the Management of Geriatric Patients 447

images and correlation with outcomes or disease phenotype. Usually, radiomics

methods are implemented in oncologic imaging field [16], but it is expected to
spread in other fields, such as cardiovascular or neuroradiology.
To date, medicine is rapidly moving toward personalized medicine, which
becomes extremely difficult and frequently impracticable in geriatric patients due to
the complexity of multimorbidity and their numerical increment. AI models have
the potential to change this setting and consequently the future of medicine, contrib-
uting to individual-based care.

17.2 Application of Artificial Intelligence in Geriatric Patients

In this chapter we will explore some of the applications of AI in geriatric population

following a somatic cranio-caudal approach. We aim to describe how can an accu-
rate and reliable AI solutions provide an effective role for the management of geri-
atric patients. Additionally, we will inspect those AI algorithms effectiveness as
compared to the traditional imaging workflow, which relies on the human health-
care providers.

17.2.1 Neurological Disorders

Neurological disorders, whose burden on healthcare services is expected to increase

due to the population growth and aging, are represented mostly by neurodegenera-
tive disorders and stroke; in particular acute ischemic stroke.
The most common neurodegenerative disorders ar Alzheimer’s disease (AD) and
Parkinson disease (PD). Considering only AD, the affected patients account for 2%
of the population over 65 years, increasing to 30% over 85 years [17].
To manage the upcoming increasing number of cases due to the aging of the
population and the subsequently unmanageable workload, new instruments need to
be evaluated and to be implemented in the clinical practice. With this aim, radiomics
features extracted from magnetic resonance imaging (MRI) of the brain combined
in ML models have been proposed as valuable instruments to improve early diagno-
sis, resulting in an early treatment, and prognosis of AD and PD [18].
In AD, the diagnosis of mild cognitive impairment (MCI) and the detection of
MCI who will convert to AD are still challenging. The first brain region to be inves-
tigated was the hippocampus. Sørensen et al. in 2016 have introduced the use of
hippocampal texture, in addition to the traditional hippocampal volume, to provide
diagnostic information for association to early cognitive loss beyond that of volu-
metric changes [19]. From texture analysis to a more comprehensive radiomics
approach, the step is short: in 2018 Luk et al. extracted 215 features from hippocam-
pus on MRI T1-W images. A support vector machine (SVM), one of the most
described ML algorithm, was implemented to differentiate MCI from healthy con-
trols, achieving an accuracy ranging from 80% to 93.3% [20]. In the same year,
448 S. C. Fanni et al.

Feng et al. changed the target for radiomics features extraction to the corpus callo-
sum, as it is a major site of disease in the late stage of AD. A logistic regression
model was implemented to analyze 385 texture features, with a modest accuracy of
70% in the detection of AD versus controls [21].
As AD is a neurodegenerative disorder with a widespread involvement of the
entire brain, the next natural step was the application of radiomics features extrac-
tion to a series of brain’s region. Nanni et al. achieved an AUC of 94% in differen-
tiating AD versus controls and an interesting 70% in detecting the patients with
MCI who faster convert to AD, combining texture and volume features of AD
brain [22].
PD is the second most common neurodegenerative disorder and, as AD, an
increasing social and economic burden is expected on our society. Shinde et al. in
2019 implemented a CNN to detect PD subject analyzing neuromelanin-sensitive
MR images. The CNN showed an interesting performance, locating the most impor-
tant site involved in the disease, differentiating PD from healthy subject with an
accuracy of 80% and even from other parkinsonian syndrome with accuracy of
85.7%. The CNN has outperformed the radiomics classifier with an accuracy of
about 60.3% [23].
As for the neurodegenerative disorders, even stroke-related burden on healthcare
services is going to increase due to aging of population, with an upcoming and wor-
rying rise in terms of mortality, disability, and economics costs [24].
Neuroimaging, using CT and MRI, plays a pivotal role even in stroke manage-
ment, as they are crucial to select subject for the most appropriate therapy. Radiomics
and machine learning algorithm are expected to manage the incoming increased
workload and to improve early diagnosis, prediction of early outcomes, and evalua-
tion of long-term prognosis [25]. As ischemic stroke accounts for approximately
85% of all stroke cases [26], we will focus on applications of AI in management of
this entity. Nonenhanced computed tomography (NECT) is the first imaging choice
in patients with episode of neurologic deficit. As far as early diagnosis is vital to
rapidly treat the patients with the thrombolytic agents, it still remains extremely
challenging because the changes in ischemic area often are not easily detectable.
Texture analysis has been implemented in order to differentiate healthy tissue from
ischemic lesion. With this purpose, Peter et al. built a machine learning model with
six texture features extracted from NECT, achieving an AUC of 0.82 [27].
Texture features were also evaluated as a predictor for secondary intracranial
hemorrhage in patients with acute ischemic stroke. In a study of Kassner et al. tex-
ture parameters extracted from MR T1-weighted images achieved an AUC > 0.75,
resulting in a great predictive ability for early outcomes and outperforming visual
enhancement score (AUC < 0.6) [28]. Furthermore, radiomics features were ana-
lyzed to evaluate the long-term prognosis. Betrouni et al. demonstrated a correlation
between the 6-month cognitive impairment and radiomics features extracted at 72 h
after stroke from MR images of hippocampus and entorhinal cortex. The support
vector machine algorithm achieved an interesting AUC of 0.9 [29].
17 The Role of Artificial Intelligence (AI) in the Management of Geriatric Patients 449

17.2.2 Lung and Cardiovascular Diseases

In this section, we will be addressing lung and cardiovascular diseases which can
benefit from the potential role of AI in the imaging management of these disease.
Chest CT is a medical imaging technique widely performed in elder people,
mostly to diagnose, stage, or assess therapy response of lung cancer, to evaluate
other pulmonary disease such as chronic obstructive pulmonary disease (COPD) or
cardiovascular disease. Building upon this assumption, and in order to take advan-
tage of the large amounts of hidden data not fully exploited in these chest CTs,
Carneiro et al. developed a radiomics and a deep-learning approach to predict the
5-year all-cause mortality. The following structures were segmented to extract
radiomic features from CT images: lungs, heart, epicardial fat, aorta, spinal column,
body fat, and muscles. The deep learning approach, based on two different types of
CNNs, achieved a mean classification AUC of 69%, outperforming the radiomics
approach, which still presented a good performance (64.6%). Furthermore, the pre-
diction accuracy was similar to currently used clinical risk scores despite the small
cohort of patients enrolled and the exclusion from the models of strongly predictive
variable as gender or age [30].
Among all the lung disease, COPD has received a great deal of interest, as it is
one of the most important cause of death in elder people, and in the next two
decades, it is expected to become the leading cause [31]. Furthermore, COPD is a
known major risk factor for lung cancer, as they share similar physiopathology and
etiology, such as smoking cigarettes [32]. COPD has a heterogeneous CT pattern
resulting from the variable combinations of centrilobular emphysema and airway
disease [33]. This complexity and the ongoing increase of incidence make it neces-
sary to investigate new tools, in order to improve patient’s outcome through an early
diagnosis. The first step was represented by quantitative CT (QCT), which is defined
as the study of computer-aided methods able to quantify handcrafted features on
CT, as the amount of emphysema or airway abnormalities [34]. Though effective,
these methods are often time-consuming, consider only a few handcrafted features,
and are prone to variability [35]; therefore, more dedicated effort need to be done to
explore new hands-on and less time-consuming methods, such as radiomics and
machine learning algorithm. Ginsburg et al. in 2012 extracted texture features to
train a multiple logistic regression classifier able to differentiate effectively between
smokers even without emphysema and never-smokers’ lungs [36]. Lafata et al.
extracted 39 radiomics features to quantify lung function from CT images. The
radiomics signature was then compared to spirometry test as a reference standard,
demonstrating an interesting correlation in particular with FEV1 [37].
Another medical imaging technique progressively more used over the years is
cardiac computed tomography angiography (CCTA), which is extensively per-
formed to rule out coronary artery disease (CAD) [38]. AI may have a potential role
in reducing the time of image analysis, lightening the workload of radiologists,
ranging from diagnostic to prognostic tasks [39]. For instance, Muscogiuri et al.
450 S. C. Fanni et al.

investigated the potential role of a CNN for the classification of CAD-RADS, which
is a standardized method to describe coronary artery disease ranging from 0 (absence
of stenosis) to 5 (at least one totally occluded coronary artery) [40]. The algorithm
effectively distinguishes CAD-RADS ≥1 from 0 with an average time of analysis
much shorter compared to radiologists, which is an important result assuming an
increase of CCTA in the next few years [41]. Another important quantitative param-
eter and predictor for adverse cardiovascular events is the coronary artery calcium
score (CACS) [42]. Wolterink et al. described the implementation of a CNN to
evaluate the CACS on CCTA, achieving an interclass correlation of 0.94 compared
to the reference standard [43].
Additionally, CCTA could be source of parameters to build prognostication
model. Motwani et al. in 2016 developed an ML model for prognostic stratification
in patients followed up for 5 years combining 44 parameters extracted from CCTA
and 25 clinical parameters. The severity score computed by the model achieved an
AUC of 0.79, outperforming traditional prognostic score such as the Framingham
(0.61) and Duke Index (0.62) [44].

17.2.3 Abdomen

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy in both
genders [45]. In spite of the availability of screening programs today, about 60–70%
of CRC are still diagnosed at advanced stages [46].
Therefore, AI could be implemented to improve the diagnostic performance of
routinary screening, such as colonoscopy or computed tomographic colonography
(CTC) [47]. One of the challenges of CTC is the detection of flat colorectal ade-
noma. In 2008 Taylor et al. developed a computer-aided detection system to seek the
flat early-stage CRC on supine and prone CTC images. The algorithm achieved a
sensitivity of 83.3% and 54.1%, respectively, with 0 and 1 sphericity values [48].
Apart from the detection, AI could improve colorectal lesion classification into neo-
plastic and non-neoplastic findings. Song et al. in 2014 demonstrated a significant
improvement in classification of colorectal lesion by adding to image intensity a
texture features analysis, with the AUC rising up from 0.74 to 0.85 [49].
Recently, Grosu et al. implemented an ML method to distinguish more specifi-
cally benign and precancerous lesions detected on CTC of asymptomatic patients,
with an extremely interesting AUC of 0.91 [50].
Another abdominal oncologic condition whose incidence is expected to increase
in the next few years is the hepatocellular carcinoma (HCC). Contrary to CRC,
HCC develops from a specific pathologic substrate, the cirrhotic liver, thus leading
to screening not of the entire population but only in selected patients. Ultrasound
(US) is the main imaging tool to detect new lesion in cirrhotic patients.
To determine the presence of cirrhosis, Liu et al. developed an algorithm based
on the analysis of liver capsule. Using the analysis of liver capsule contour, they
were able to determine the presence or absence of cirrhosis, with an area under the
curve of 0.97 [51]. Once cirrhosis is identified, the challenge is to distinguish benign
from malignant lesions. Bharti et al. proposed an ANN model to differentiate four
17 The Role of Artificial Intelligence (AI) in the Management of Geriatric Patients 451

stages of liver disease using data obtained from US images: normal liver, chronic
liver disease, cirrhosis, and HCC. The classification accuracy of the model was
96.6% [52]. Further, images of contrast-enhanced US were used to develop more
accurate models. Streba et al. implemented an ANN model to classify HCC, liver
metastases, hemangioma, and focal fatty changes with a 94.5% accuracy [53].
When a follow-up ultrasound demonstrates a new lesion suspicious for HCC, other
imaging studies like CT or MRI are required to achieve a characterization. AI could
play a role in the hepatic nodule with an indeterminate behavior which could help
to avoid invasive biopsy. For this purpose, Mokrane et al. retrospectively collect 178
patients with indeterminate nodules subjected to biopsy and developed a DL algo-
rithm to classify nodules as HCC or non-HCC lesion, with an optimistic AUC
of 0.70.

17.2.4 Prostate

Prostate carcinoma represents the most common cancer in men worldwide and,
despite its low aggressivity, is the third cause of death cancer-related [54].
Overdiagnosis is usually a common issue in the diagnostic process of prostatic ade-
nocarcinoma, which leads to an increased burden on the healthcare system. Accurate
prostate segmentation as well as its volume estimation is considered to provide
invaluable information for the process of diagnosis and clinical management of
benign prostatic hyperplasia (BPH) versus the prostatic carcinoma. Therefore, that
can improve BPH treatment, surgical planning, and predictions of PCa prognosis
[55]. There are multiple use case domains of using AI or ML in prostate cancer as
the detection of prostate cancer with high accuracy both in peripheral and transi-
tional zone, characterization of cancer according to its biological aggressiveness
into clinically significant and nonsignificant disease, identification of patients with
metastatic prostate cancer as early as possible, establishing the radiologic–histo-
pathologic correlation to provide biology-based validation of AI models, prediction
of the risk of disease recurrence and prediction of treatment response in case of
radiation therapy or post-prostatectomy as well as the possibility of using
AI-powered patient stratification tools for enrollment in Active Surveillance
programs.
Accuracy of prostate lesion detection, segmentation, and volume estimation is
important at different stages of PCa management. Lesion detection identifies regions
for biopsy. Accurate segmentation is crucial for improved fusion biopsy yields as
well as improving radiotherapy delivery. Volume estimation can predict prognosis
after prostatectomy [56].
The current challenge is the differentiation between aggressive and nonaggres-
sive disease to selectively treat only aggressive type and avoid overdiagnosis and
overtreatment. As prostate cancer is a typical elderly disease, its prevalence and
incidence are expected to dramatically increase exacerbating the challenge already
mentioned. Artificial intelligence could be a solution to achieve the full potential of
multiparametric prostate MRI (mpMRI) as a screening, diagnostic, and prognos-
tic tool.
452 S. C. Fanni et al.

In 2017, Karimi et al. implemented an ML algorithm to differentiate between the

benign and malignant lesions. The performance was significantly improved by the
combination of the ML algorithm already implemented with a CNN, achieving an
AUC of 0.87 [57]. Once a prostate lesion is identified, a correct risk-stratification is
vital to guide the decision-making for the possible therapeutic options. With this
goal, Zhang et al. in 2019 developed a DL model to predict a Gleason score ≥7 from
mpMRI in patients treated with robotic prostatectomy. Adopting lesion ROI defini-
tion by adding random cropping into the data augmentation, they were able to fur-
ther improve the robustness of the model with less potential ROI inconsistency. The
algorithm performance was compared to the radiologists one using PI-RADS, with
at least a similar result (AUC 0.73 vs. 0.71) [58].
In 2020 Li et al. adopted another approach by extracting radiomics features from
biparametric prostate MRI to build a model for predicting the clinically significant
prostate cancer. The radiomics features extracted and selected were incorporated
into the RAD-SCORE, as the sum of the weighted features. The RAD-SCORE
achieved an AUC of 0.98 in the test set, a similar result was obtained when the
RAD-SCORE was combined with clinical parameters such as age, prostate volume,
or serum PSA [59].
Artificial intelligence algorithm has been applied for automatic and accurate
prostate segmentation, which is the first step to compute prostate volume or to
extract radiomics features.
In 2017 Rundo et al. used an ML technique to segment prostate on T1-weighted
and T2-weighted images from mpMRI. The performance was evaluated with the
Sørensen–Dice coefficient, which is a measure of the spatial intersection between
the automated segmentation and the ground-truth label. In this paper a great Dice
coefficient of 0.91 was achieved [60].

17.2.5 Musculoskeletal

Musculoskeletal radiology is yet another field which could benefit of AI integration

in clinical practice since fractures are one of the most common cause of hospitaliza-
tion, morbidity, and mortality in the elderly. Among many types of fractures, one of
the most common is the hip fracture, with a lifetime risk of 27.5 in the women [61].
One issue is the 3–10% rate of occult hip fractures, requiring further investigation
as CT or MRI, with a subsequently increased cost and delayed diagnosis [62].
Hence, Mawatari et al. developed a CNN to detect the hip fractures on hip radio-
graphs. Authors compared the CNN performance to seven radiologist readers with
different clinical experiences. The CNN achieved an AUC of 88%, while the radi-
ologist’s performance ranged from 0.698 to 0.92. Therefore, the most experienced
radiologist outperformed the CNN. However, the authors demonstrated an increased
performance of all the reader when consulting the CNN outputs, even for the most
experienced one, whose AUC increased to 0.934. Therefore, AI/ML can be a useful
asset in the radiologist’s daily toolbox [63].
17 The Role of Artificial Intelligence (AI) in the Management of Geriatric Patients 453

A further type of fracture common in the elderly are the vertebral fractures [64].
When a vertebral fracture is diagnosed, it is challenging to differentiate the benign
from malignant causes, requiring a different pathway of management.
Li et al. trained a CNN with CT images from 433 patients with benign or malig-
nant fracture. The CNN achieved a good result, with an accuracy of 85% [65].

17.3 Conclusion

It is expected that in the upcoming years the old people will increasingly represent
the typical patients accessing healthcare services. Therefore, there is an emerging
need for handling that increased workload on the healthcare systems. With the
advent of many AI algorithms, the potential of AI applications in geriatric patient
management shows a promising spectrum of clinically beneficial uses. The applica-
tions can be employed in diverse practical domains as patients’ screening, imaging
acquisition, pre-reporting, and the further diagnostic process.

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