Radiological Imaging in Brain Disorders:

An Overview 2
Valentina Ferrazzoli and Kshitij Mankad

Contents
2.1  euroimaging Modalities and Techniques
N    3
2.1.1 Computed Tomography (CT)    4
2.1.2 Magnetic Resonance Imaging (MRI)    4
2.2 Radiological Imaging in Neurodegenerative Diseases    5
2.3 Radiological Imaging in Movement Disorders    7
2.4 Radiological Imaging in Epilepsy    7
2.5 Radiological Imaging in Neuro-Oncology 10
References 12

2.1 Neuroimaging Modalities and Techniques

The key role of neuroimaging in brain disorders is to assist clinical management by

either making a precise diagnosis or providing clinically relevant differential diag-
noses. There is a marked diversity of neuropathologies spanning a constellation of
conditions including vascular, infectious-inflammatory, degenerative and neoplastic
entities, and the clinical presentations can often be quite nonspecific, hence the key
role of neuroimaging is formulating a management plan. Cranial Ultrasonography
(US), Computed Tomography (CT) and Magnetic Resonance (MR) are the cur-
rently available modalities of neuroimaging, each with its specific strengths and
limitations. Overall, MR Imaging (MRI) is the most useful technique to study the
brain, given its higher soft tissue contrast, although CT has a central role still in
acute imaging and is also the best technique to investigate for associated bony

V. Ferrazzoli (*)
Department of Biomedicine and Prevention, Tor Vergata University Hospital, Rome, Italy
K. Mankad
Department of Radiology, Great Ormond Street Hospital NHS Foundation Trust, London, UK

© Springer Nature Switzerland AG 2019 3

F. Fraioli (ed.), PET/CT in Brain Disorders, Clinicians’ Guides to Radionuclide
Hybrid Imaging, https://doi.org/10.1007/978-3-030-01523-7_2
4 V. Ferrazzoli and K. Mankad

disorders. Cranial US has a vital role in foetal and neonatal imaging given its bed-
side ease and the presence of a good acoustic window—the skull foramina in this
population. This chapter focuses on those clinical applications of neuroimaging that
complement the practice of nuclear medicine with special relevance to CT and MRI.

2.1.1 Computed Tomography (CT)

The advent of fast multi-detector CT scanners with superior multi-reformat capabili-

ties and their universally easy availability makes it the primary imaging modality in
acute care. The acquisition protocol consists of contiguous thin sections (1 mm or
less) or overlapping axial slices (slice thickness no greater than 5 mm). CT is primar-
ily indicated in cases of sudden onset of new symptoms or deterioration, in the assess-
ment of intracranial shunts or in the immediate post-neurosurgical evaluation [1]. It is
mainly useful to detect calcifications and to establish the presence of blood within a
lesion or in acute head trauma. It can also assist with characterising brain tumours, by
showing increased density in hypercellular tumours and presence of calcification and
or haemorrhage in tumour matrices. CT scan also provides a much better assessment
of the bones of the skull vault and the skull base which can be secondarily affected in
some diseases, such as metastases or lymphomas. In some cases, the administration of
iodinated contrast medium can provide additional information in the assessment of
the blood brain barrier or, through CT angiography (CTA) technique, in the noninva-
sive investigation of intracranial vessels and vascular malformations.

2.1.2 Magnetic Resonance Imaging (MRI)

MRI is the diagnostic tool of choice in investigating the brain, owing to its superior
soft tissue contrast resolution. MRI protocols are tailored on diagnostic indications
and all provide multiparametric information. The standard protocol includes
T2-weighted (w) sequences, with and without CSF signal suppression (FLAIR),
T1-w sequences and diffusion-weighted imaging (DWI). Susceptibility-weighted
imaging (SWI) is a helpful adjunct in a large spectrum of diseases in order to iden-
tify blood, calcification or iron deposition. The use of different acquisition planes
for a three-dimensional evaluation is always useful: in particular the acquisition of
sagittal plane to investigate midline structures and coronal acquisition on temporal
lobes for the assessment of hippocampal and parahippocampal regions. Three-
dimensional T1-w sequences are also commonly employed in neuro-oncology and
epilepsy protocols, in guiding neurosurgery (intraoperative neuronavigation) and
also for their accuracy in identifying tiny lesions, to facilitate volumetric measure-
ments of tumour burden, and for better alignment of tumour regions on subsequent
follow-up examinations [2].

2.1.2.1 Perfusion MRI

MR perfusion imaging is an increasingly common mean for the evaluation of a
variety of pathologies mainly tumours and ischaemia. Three techniques are now
2 Radiological Imaging in Brain Disorders: An Overview 5

available: two of them use T1- or T2-weighted changes after the injection of a
gadolinium-based contrast agent, respectively, dynamic contrast-enhanced (DCE)
MRI and dynamic susceptibility contrast-enhanced (DSC) MRI, and a third, arte-
rial spin-labelling perfusion (ASL-MRp), in which magnetically labelled arterial
blood water is used as an endogenous contrast agent. The main application of
perfusion in neuro-oncology is in providing additional information for the differ-
ential diagnosis, in particular between lymphomas and glioblastomas or metasta-
ses, for the assessment of brain tumour grade and for the evaluation of treatment
response. In acute stroke it can be used together with DWI for the identification of
potentially salvageable brain tissue or even to assess vasospasm in particular con-
ditions [3].

2.1.2.2 MR Spectroscopy

Spectroscopy provides information about normal and pathological tissue compo-
nents by an analysis of the chemical environment of the brain. The most commonly
studied metabolites are choline (Cho), a marker of cell membrane integrity and cell
proliferation; creatine (Cr), a marker of cell metabolism; N-acetyl-aspartate (NAA),
a marker of neuronal integrity; lactate (Lac), a marker of anaerobiosis; and lipids
(Lip), which correlate with membrane disintegration. The typical indications
include detecting the presence of neoplasms, grading of gliomas (low versus high
grade), evaluation of temporal lobe epilepsy and certain neurometabolic and neuro-
degenerative diseases [4].

2.1.2.3 Diffusion Tensor Imaging

Diffusion tensor imaging (DTI) is useful in the preoperative planning for oncology
and epilepsy. The technique enables the 3D localisation, orientation and anisotropy
of the white matter tracts of the brain and their relationship to the lesion under man-
agement [5].

2.1.2.4 Functional MRI (f-MRI)

f-MRI uses blood oxygenation level-dependent imaging (BOLD) technique, which
is based on the localisation of hemodynamic changes caused by regionally increased
neuronal activity during a cognitive task. This information is useful to determine the
hemispheric dominance and the presence of eloquent cortex in relation to a focal
lesion to plan surgical treatment [6].

2.2 Radiological Imaging in Neurodegenerative Diseases

Dementia, as a prototypical group of neurodegenerative disorders, can be subclassi-

fied based on certain neuroimaging criteria. Alzheimer disease (AD), dementia with
Lewy bodies (DBL), frontotemporal dementia (FTD) and vascular dementia are its
commonly encountered subtypes. Anatomic neuroimaging with MRI can differenti-
ate normal age-related degenerative processes from early signs of dementia, exclude
alternatives causes and identify specific patterns of brain volume loss that can sup-
port the clinical diagnosis [7]. Functional and metabolic imaging is suggested for
6 V. Ferrazzoli and K. Mankad

a b c

d e f

Fig. 2.1 Neurodegenerative diseases. (a) Vascular dementia in a 69-year-old patient. (a) Axial
T2-w image shows moderate diffuse small vessel disease (arrow heads) and generalised brain
atrophy. (b, c) Mild cognitive impairment (MCI) and Alzheimer disease (AD). (b) Mild and (c)
severe atrophy, with reduced volume of the hippocampi (arrows) and enlargement of the liquoral
spaces, is seen in patients with MCI and AD. Coronal T1-w images better allow the assessment of
medial temporal lobe. (d, e, f) Frontotemporal dementia. (d) Axial and (e) coronal T1-w images
show disproportionate atrophy of the frontal and temporal lobes, with relative sparing of the pari-
etal and occipital lobes in a 67-year-old. (f) Coronal T2-w image shows a severe atrophy of frontal
and temporal lobes in a 70-year-old (Figures are courtesy of Dr. H. Hyare, University College of
London Hospital, NHS Foundation Trust, London)

problem-solving purposes, and a multimodality approach allows an earlier and

more confident evaluation [8]. Initially it is important to evaluate if there is a spe-
cific pattern of volume loss with a lobar predominance, looking for enlarged tempo-
ral and/or frontal ventricular horns, widened sulci and thinned gyri. Disproportionate
atrophy of the medial temporal lobes is generally the earliest sign identified in AD,
and its progression correlates well with clinical progression of cognitive impair-
ment [9]. The imaging assessment should therefore include the hippocampi, which
appear atrophic, the entorhinal cortex and the perirhinal cortex in the coronal plane.
AD changes involve parietal and frontal lobes subsequently, whereas the occipital
lobes and sensorimotor cortices are relatively spared.
Anatomic imaging findings in FTD on the other hand show symmetric or asym-
metric frontal or temporal lobe atrophy, with relative sparing of the parietal and
occipital lobes; these signs are subtle at the early stage, but later they can be severe
with a ‘knife blade’ appearance of the atrophied gyri [10]. The pattern of volume
loss in DLB is nonspecific, with a relative preservation of the hippocampi [11].
Figure 2.1 shows pattern of volume loss in different types of dementia.
2 Radiological Imaging in Brain Disorders: An Overview 7

2.3 Radiological Imaging in Movement Disorders

MRI is used to evaluate certain key structures of the brain in parkinsonian disorders,
namely, the basal ganglia (caudate, putamen and globus pallidus) and the midbrain,
with particular focus on the substantia nigra, the pons and the cerebellum.
The primary step is to exclude structural pathologies involving these areas, for
instance, neoplasms, haemorrhagic or ischaemic lesions involving the basal ganglia [12].
Change in the signal pattern at the substantia nigra on susceptibility-weighted
MR sequences, relating to an increased iron content, is the most typical feature
described in Parkinson’s disease (idiopathic parkinsonism). This is eloquently
described as the absent swallow tail sign (the swallow tail sign is present in nor-
mal individuals as a comma-shaped focus of high signal on susceptibility-
weighted sequences in the posterior 1/3 of the substantia nigra). A relative
reduction in putaminal volume is also described as an early feature, though it is
not specific [13].
In other parkinsonian conditions such as multisystem atrophy (MSA), the puta-
men is particularly involved, initially with reduced T2 signal along its lateral edge
due to iron deposition, with atrophy and even frank gliosis in later stages. This
condition is typically accompanied by degeneration of the pons and cerebellum,
with associated prominence of the longitudinal and transverse pontine fibres, giving
the typical ‘hot cross bun’ sign of the hind brain in MSA (Fig. 2.2a).
Conversely, in progressive supranuclear palsy (PSP), there is selective atrophy of
the midbrain giving rise to the ‘hummingbird’ sign on a midline sagittal section
(Fig. 2.2b). This is accompanied by a widening of the interpeduncular fossa as well
as signal abnormality in the superior cerebellar peduncles [14]; this appearances
result in the “Mickey Mouse sign” in axial plan (Fig. 2.2c).
Another condition in this respect is corticobasal degeneration (CBD), that pres-
ents with movement disorders and cognitive decline and shows selective brain vol-
ume loss in the posterior parietal regions (Fig. 2.2d, e).
In paediatric practice, there is a wide differential to movement disorders, and
once again MRI has a primary role in the evaluation of relevant structures such as
the basal ganglia, in conditions such as neuronal brain iron accumulation
(NBIA) (Fig. 2.2f).

2.4 Radiological Imaging in Epilepsy

The role of neuroimaging in epilepsy is multifold: to detect a causative structural

lesion, to guide management and to monitor disease. There is a vast and diverse
constellation of conditions that can cause seizures and radiology helps in their
identification. These entities include malformations of cortical development,
tumours, stroke, infections, traumatic brain injuries, vascular malformations, pri-
mary or secondary mesial temporal sclerosis (MTS), phakomatoses, hypoxic isch-
emic encephalopathy and inborn error of metabolism [15]. Twenty to 30% of
patients with temporal lobe epilepsy and 20–40% of patients with extra-temporal
8 V. Ferrazzoli and K. Mankad

a b c

d e f

Fig. 2.2 Movement disorders. (a) Multisystem atrophy (MSA). T2-w axial image demonstrates
the presence of pontine and cerebellar atrophy with degeneration of pontocerebellar tracts passing
through the middle cerebellar peduncles that results in the ‘hot cross bun sign’ at the level of the
pons (black lines in magnification). (b, c) Progressive sopranuclear palsy (PSP). (b) Sagittal plan
shows marked midbrain and tegmental atrophy compared with the pons which results in the
appearance referred as “hummingbird sign. (c) Axial T2-w image demonstrate atrophy of the mid-
brain, involving the cerebral peduncles and resulting in the “Mickey Mouse sign”. (d, e)
Corticobasal degeneration (CBD). (d) Axial T2-w image and (e) parasagittal T1-w image show
cortical atrophy involving predominantly the pre- and postcentral gyri and the superior parietal
lobule. (f) Susceptibility-weighted imaging (SWI) demonstrates iron accumulation within the
globi pallidi in a 5-year-old patient with movement disorder (ataxia), in keeping with neurodegen-
eration with brain iron accumulation (NBIA)

epilepsy have no clear lesion visible on a standard conventional MRI [16]; there-
fore, a dedicated epilepsy protocol and a meticulous review of the scan is essential
as structural lesions can be completely resected with long-term seizure freedom.
Lesion detection and characterisation are improved with 3T-MRI, especially for
cortical lesions. Moreover T2-w and FLAIR coronal oblique images with thin
slices (commonly 2–3 mm slice thickness), acquired perpendicular to the hippo-
campal long axis, in combination with a coronal 3D inversion recovery sequence
are crucial for the identification of subtle cortical abnormalities, disturbances in
cortical migration and MTS [17]. The latter comprises of gliosis, atrophy and loss
of the internal architecture of the hippocampus; atrophy may be present in the other
structures of limbic system along with increased T2-w signal in the mesial tempo-
ral region. Many times a retrospective review of the MR images after nuclear imag-
ing may reveal a subtle cortical abnormality overlooked at the initial MRI
interpretation. Focal epileptogenic lesions, as haemorrhage and vascular
2 Radiological Imaging in Brain Disorders: An Overview 9

a b c

d e f

g h i

Fig. 2.3 Epilepsy in paediatric patients. (a–c) A 6-year-old boy with seizures. Axial T2-wi (a), coro-
nal FLAIR (b) and T1-wi (c) show frontal bilateral heterotopic grey matter (white arrows) extending
from the ventricular surface to the cortex in keeping with FCD. (d–f) A 2-year-old boy with temporal
epilepsy. Coronal FLAIR (e) and T1-w (f) images oriented on the temporal pole (d) show a smaller
left hippocampus which has altered signal and poor detail of the internal architecture: the temporal
horn of the left ventricle is consequently enlarged. Symptoms resolved after right pole resection.
(g–i) A 7-year-old girl. Axial T1 and T2-wi and coronal T1-wi show a cortical/subcortical non-
enhancing lesion in the left inferior frontal gyrus in keeping with DNET undergoing surgery

malformations, can be better detected on susceptibility-weighted sequences [18].

Contrast injection is useful for the evaluation of known or suspected focal brain
lesions or in neurocutaneous syndromes; therefore its use depends on clinical his-
tory, especially in the paediatric population. MRI can also show transient seizure-
related signal changes, which can mimic other pathologic conditions but normalise
over time, and permanent brain injury, including cortical volume loss, laminar
necrosis and hippocampal sclerosis [17]. Figure 2.3 shows different causes of epi-
lepsy in paediatric patients.
10 V. Ferrazzoli and K. Mankad

2.5 Radiological Imaging in Neuro-Oncology

In neuro-oncology diagnostic imaging has to provide, in the first instance, the dif-
ferential diagnosis between primary or secondary neoplasms and then additional
clues for the further management. CT maintains a role in detecting calcifications,
typically present in different types of tumours as meningioma, oligodendrogliomas,
germinomas, haemorrhages and tumour-related bone changes. However MRI is the
modality of choice in the comprehensive characterisation of tumours. Conventional
imaging provides essential information about the structure of the tumour, the pres-
ence of necrosis, the presence and the type of the enhancement, multifocality, lep-
tomeningeal and/or subependymal seeding; nevertheless these features cannot be
specific. DWI, being sensitive to random motion of water molecules, can give infor-
mation about cellularity, allowing the identification of hypercellular lesions with
restricted diffusion and low apparent diffusion coefficient (ADC), as typical lym-
phomas and embryonal tumours and sometimes germ cells tumour and pineoblasto-
mas (Fig. 2.4a, b). The hypercellularity in these cases is also demonstrated as
hyperdensity on CT scanning (Fig. 2.4c). Perfusion-weighted sequences and MR
spectroscopy can provide further information of the tumour environment assisting
with its grading, characterisation and response to therapy.
As an example, the differentiation between lymphomas and high-grade gliomas
(HGG) is crucial considering their different managements. This differentiation is
difficult based on conventional sequences, as lymphomas may not have their typical
appearances of homogeneous enhancement with involvement of the corpus callo-
sum, lack of calcifications or haemorrhages. Herein, diffusion-weighted imaging
helps by showing lower ADC in lymphomas and lower perfusion on PWI that
reflects the leakage of contrast in the interstitial space [19, 20] (Fig. 2.4d–f). HGG
can be differentiated using these techniques as they usually demonstrate necrotic-
ring enhancement, a peritumoral area of signal abnormality with low ADC, increased
CHO-NAA ratio on MRS and higher vascularity on PWI [21, 22] (Fig. 2.4g–i).
Another practical application of MRI is the noninvasive grading of gliomas.
HGGs demonstrate lower ADC, higher CHO-NAA ratio and relative cerebral blood
volume on PWI compared with LGG [21]. These features can even be used to rec-
ognise areas with greater anaplasia within a lesion to target biopsy.
The other challenge for diagnostic imaging is response assessment of tumours to
various and emerging forms of therapy. In this context it is useful to advocate mul-
timodal imaging, using a combination of conventional imaging, along with perfu-
sion MRI and PET imaging. Comparing true tumour progression to therapy-related
necrosis or pseudo progression, for instance, lower relative blood volume on PWI is
noted in the latter. Another important role of MRI is the identification of tumour
pseudo response after anti-angiogenic treatment. These differentiations are not
always obvious, and then repeat imaging is recommended to evaluate for persisting
or progressing changes in 3 months’ time to confirm true progression [23].
2 Radiological Imaging in Brain Disorders: An Overview 11

a b c

d e f

g h i

Fig. 2.4 Imaging of brain tumours. (a–c) Posterior fossa lesion in a 3.5-year-old child. (a) Axial
post-contrast T1-wi shows a large midline enhancing mass centred in the cerebellum causing
effacement of the fourth ventricle. The lesion has restricted diffusion in keeping with hypercellu-
larity (b) confirmed by ADC maps (not shown); this finding is congruous with the hyperdensity of
the lesion in CT scan (c). These appearances are in keeping with the histological diagnosis of
medulloblastoma. (d–f) A large mass in a 39 years old man. (d, e) DWI and corresponding ADC
map show a restricting lesion with very low ADC values centered in the right basal ganglia; (f)
axial post-contrast T1w image shows intense enhancement of the lesion in keeping with lym-
phoma. (g–i) A large mass in a 65-year-old man. (g) Axial T2, (h) coronal FLAIR and (i) axial
post-contrast T1-w images show a heterogeneous enhancing mass centred in the left deep grey
matter, with a large area of necrosis, confirmed on histology to be a glioblastoma multiforme
(Figures d–i are courtesy of Dr. H. Hyare, University College of London Hospital, NHS Foundation
Trust, London)
12 V. Ferrazzoli and K. Mankad

Key Points

• Key role of neuroimaging is to assist clinical management by either making

a precise diagnosis or providing clinically relevant differential diagnosis.
• Computed tomography (CT) is mainly used in cases of sudden onset of
new symptoms or deterioration, immediately after neurosurgery, to rule out
the presence of calcifications, hemorrhages, or bone alterations.
• Magnetic resonance imaging (MRI) is the most useful technique to inves-
tigate the brain, through morphologic and advanced imaging.
• Advanced MR imaging comprises perfusion imaging, mainly used in
tumours and ischemia; spectroscopy, which evaluates brain tissue metabo-
lites; and diffusion tensor imaging, employed in pre-surgical planning to
study white matter tracts.
• In neurodegenerative diseases, MRI can differentiate normal age-related
degenerative processes from early signs of dementia, exclude alternatives
causes, and identify specific patterns of brain volume loss that can support
the clinical diagnosis.
• In motor disorders MRI is helpful in evaluating key structures, as the basal
ganglia (caudate, putamen, and globus pallidus), midbrain, pons, and cer-
ebellum, that can demonstrate signal changes and atrophy.
• The role of neuroimaging in epilepsy is multifold: to detect a causative
structural lesion, to guide management, and to monitor disease.
• The combined use of MRI and nuclear imaging in epilepsy management is
crucial, as the retrospective review of the MR images after nuclear imaging
may reveal a subtle cortical abnormality initially overlooked.
• In neuro-oncology diagnostic imaging has to provide, in the first instance,
the differential diagnosis between primary or secondary neoplasms and
then additional clues for the further management.
• Multimodal imaging, using PET imaging in combination with conven-
tional MRI and advanced MR techniques, helps in assessing tumour
response to therapies.

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