State-Of-The-Art Neonatal Cerebral Ultrasound: Technique and Reporting
State-Of-The-Art Neonatal Cerebral Ultrasound: Technique and Reporting
State-Of-The-Art Neonatal Cerebral Ultrasound: Technique and Reporting
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In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap,
non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major
abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation,
and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and
ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke,
developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5–18 MHz),
3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing.
Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss
how to perform a dedicated state-of-the-art neonatal CUS, and we provide suggestions for structured reporting and quality assessment.
INTRODUCTION Doppler sonography, with which the patency of both arteries and
Cerebral ultrasound (CUS) is still the first-line neuroimaging veins, flow velocities, and variant anatomy can be assessed.21
modality to study the neonatal brain. It is less expensive and Doppler sonography is highly specific to rule out sinovenous
burdensome than magnetic resonance imaging (MRI), which thrombosis at vulnerable vessels.22,23 With modern Doppler
requires patient transport and sometimes sedation. CUS can be techniques, we can also quantify low flow velocities in smaller
performed bedside with acceptable disturbance to the infant. The vessels.24 Despite the fact that MRI has become more widely
procedure is radiation-free and can be initiated directly after birth, available and in some conditions is still the gold standard for
providing quick images in real time. Serial imaging can provide diagnosing various neonatal brain injuries, CUS truly deserves a
valuable information about the timing and evolution of brain place in brain imaging for its options and accuracy. This special
lesions during the course of brain maturation.1,2 Since the article aims to provide a toolkit for structured neonatal CUS
introduction of CUS in neonatal care in the late 1970s,3 its quality imaging, reporting, and quality assessment.
has dramatically improved. Modern US systems provide increas-
ingly higher resolution and faster image processing. In the past,
CUS exams were mostly performed to depict the ventricular INDICATIONS FOR CUS
system and to diagnose intraventricular hemorrhage (IVH) and Postnatal screening with CUS is indicated for all newborns at risk
periventricular cysts.3–6 Currently, CUS provides more details and a of (or suspected of) brain injury. Three main categories of neonatal
trained observer can detect most neonatal hemorrhagic and brain injury are distinguished according to when it occurred
ischemic brain lesions, major congenital anomalies, and matura- (antenatal, perinatal, and postnatal; Table 1).
tional changes in both preterm and term infants.7–11 Early
identification of infants with brain injury and thus at risk of
neurodevelopmental impairment is now thought to benefit the TIMING OF CUS EXAMINATION
individual infant, because appropriate early referrals can be made In some situations, a single postnatal CUS scan suffices to either
allowing to initiate interventions aimed at improving neurological confirm or rule out a suspected abnormality. In other conditions,
outcome. The use of high-frequency transducers further improved however, such as premature birth, neonatal encephalopathy, or
visualization of both superficial and deep areas of the brain.7–12 perinatal arterial ischemic stroke, serial examination is mandatory
Additional acoustic windows: posterior fontanel, mastoid fontanel, to detect the full spectrum of lesional change.2
temporal window, and foramen magnum, extended visualization
to areas less accessible via the most commonly used anterior Prematurity
fontanel (AF), resulting in a more reliable detection of abnorm- In preterm infants born before 28 weeks of gestation or with or a
alities.13–20 Neonatal CUS examinations now routinely include birth weight <1000 g, serial CUS is recommended on days 1, 3, 7,
1
Department of Neonatology, University Medical Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, The Netherlands; 2Department of Neonatology, Leiden University
Medical Center, Leiden, The Netherlands; 3Department of Neonatology, Helios Klinikum Berlin Buch, Berlin, Germany and 4Department Clinical Science Intervention and
Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
Correspondence: Jeroen Dudink ([email protected])
Members of eurUS.brain are listed at the end of the paper.
Antenatal Abnormal fetal neuroimaging, twin-related problems, intrauterine intervention, antenatal infection (with CMV, Toxoplasmosis, Herpes,
Rubella, Syphilis, or other neurotrophic pathogens), fetomaternal transfusion, maternal drug abuse, maternal accidents, and severe illness
Perinatal Need for prolonged resuscitation, hypoxic–ischemic encephalopathy, prematurity, very low birth weight, small for gestational age,
microcephaly and macrocephaly, suspected (genetic) syndrome
Postnatal Seizures, central apnea, encephalopathy, sepsis/meningitis/encephalitis, unexplained clinical deterioration, unexplained drop in
hemoglobin level, symptomatic hypoglycemia, inborn errors of metabolism, preterm kernicterus, abnormal movements or tone, severe
arterial hypotension or hypertension, congenital heart disease, need for surgery, or extracorporeal membrane oxygenation
HIE day 2
HIE day 4
Fig. 1 Technique and reporting: hypoxic–ischemic encephalopathy. Intrapartum asphyxia. Term infant, born at 41 weeks’ gestation with
asphyxia and hypoxic–ischemic encephalopathy, treated with hypothermia. a, b Ultrasound on admission showing subtle increased
echogenicity of the thalami on the coronal (a) but not on the sagittal (b) images. c, d Three days later, there is clearly abnormal increased
echogenicity of the thalami in both planes (arrows), which are separated from more mildly echogenic basal ganglia by a band of low
echogenicity, representing the posterior limb of the internal capsule (arrowhead).
14, 21, and 28 and then every other week until term-equivalent identified.30,31 The scans between weeks 2 and 6 help identify
age because of a high risk of brain injury. In stable preterm infants post-hemorrhagic ventricular dilatation, white matter injury, focal
born after 28 weeks of gestation, the frequency of serial CUS can arterial infarction, sequelae of brain infection, and rare cases of
be limited to days 1, 3, 7, 14, 28, at 6 weeks, and at term- late IVH. Cystic white matter injury (also known as cystic
equivalent age.25 Additional scans outside suggested schedules periventricular leukomalacia) may become apparent within 14 days
should be performed whenever clinically indicated. The first CUS after the insult, although occasionally small cysts may develop
after admission serves to rule out antenatal brain injury and up to 6 weeks after birth.32 Therefore, carefully performed
congenital malformation.25 The scans during the first week of life serial scanning with a high-resolution probe (≥7.5 MHz) after
aim to detect germinal matrix–IVH, periventricular hemorrhagic 2 weeks of life is essential to detect all cases of white matter injury.
infarction, and cerebellar hemorrhage.26–30 In at least 50% of the Scanning at term-equivalent age permits assessing how the brain
affected infants, the onset of germinal matrix–IVH is on the first developed and permits identifying permanent residuals of white
day of life, and by 72 h approximately 90% of the lesions are and gray matter injury.33 The value of this late scan for the
Coronal section on admission Right parasagittal section Posterior fontanel coronal section
Fig. 2 Technique and reporting: arterial ischemic stroke. Top: term infant with focal seizures on day 2: left posterior truncal MCA stroke;
ultrasound and MRI (diffusion weighted and T2) on day 3. Bottom: vaginal breech delivery at 36 weeks’ GA, apnea, and tense fontanel at 24 h;
pallor; and lowered consciousness: posterior cerebral artery stroke following uncal herniation due to right convexity subdural hematoma (left
image on admission, other images on day 5) (arrow in the middle image: thalamic perforator stroke).
DR 80 DR 60 DR 55 DR 40
Fig. 3 Technique and reporting: optimizing scan settings. Top row: gradually increasing total gain; middle row: gradually decreasing
dynamic range settings; bottom row, left: correction of wrong time gain compensation setting at 2 cm depth; bottom row, right: different
sector widths.
multiple focus points. For standard CUS, the focus point is Sagittal and parasagittal planes. For sagittal plane scanning, the
preferably the periventricular areas. transducer is rotated 90 degrees such that the anterior part of
the brain is displayed on the left-hand side of the monitor.
Images are obtained in the midsagittal plane and two
NORMAL US ANATOMY IN STANDARD SECTIONS parasagittal planes on each side. Regarding these parasagittal
Anterior fontanel planes, it is important to mark the side of the brain that is
Images are usually obtained through the AF. With optimal visualized. The assessment of midline and near-midline struc-
settings, this displays the supratentorial structures. Standard AF tures includes: gyrus cinguli, corpus callosum, tela choroidea,
images are recorded in six coronal and five sagittal planes.1,25 In third ventricle, cavum septi pellucidi (and Verga’s ventricle),
addition to standard planes, the whole brain is scanned to obtain cavum veli interpositi, cisterns, aqueduct, fourth ventricle,
an overview of its appearance. Any suspected lesion should be cerebellum, pons, and cisterna magna. The resistance index of
visualized in both planes. Routine Doppler visualization of large the subcallosal anterior cerebral artery can be calculated.
veins and arteries should be included. A value of >0.85 suggests a low diastolic flow and could
indicate a steal phenomenon (i.e., persistent ductus arteriosus);
Coronal planes. The transducer is placed in the middle of the AF a value <0.55 suggest a high diastolic flow (“luxury perfusion” in
such that the left half of the brain is displayed on the right-hand perinatal asphyxia). The parasagittal planes allow visualization of
side of the monitor. The probe is angled forwards and backwards the lateral ventricles, the gangliothalamic “egg” (discerning
to scan the brain from the frontal lobes to the posterior parietal thalamus, posterior limb of the internal capsule, globus pallidus,
and occipital lobes. For reliable interpretation, it is crucial to obtain putamen, caudate nucleus) and uncus, fissure of Bichat, and
symmetrical images.1,25 Attention should be paid to both focal hippocampi. With the use of three outward parasagittal planes,
and bilateral abnormalities of cortex, white matter, deep gray the insula can be inspected in detail: (1) opercular, (2) insular,
matter, and ventricles. Doppler can be used not only to visualize and (3) fissural view (Fig. 5).
the basilar artery, both internal carotid arteries, the middle
(including perforators), and anterior cerebral arteries but also for Posterior fontanel
assessing major venous drainage (i.e., flow patency of the superior The posterior fontanel is located at the junction of the lambdoid
sagittal sinus, sigmoid sinus, and internal cerebral veins; Fig. 4). and sagittal suture and is often large enough for insonation.1,15
Depth The depth control changes the maximum scanning range on screen. The depth range button usually changes the
displayed image field in 1-cm gradation increments. Increasing depth means a reduction of the image resolution (the
signal needs to cover a longer distance), therefore the frame rate and the resolution are both lower. The optimal depth
depends on beam penetration and therefore on transducer frequency
Dynamic range (DR) The DR controls the range of shades of gray displayed on the screen to be increased or decreased. It can make an image
look either very black and white or very gray. It can remove low-level echoes and result in an image with more contrast
Focus point(s) The focus (point) determines the depth at which the ultrasound beam is focused and creates the best possible lateral
resolution at that depth. It is often marked by an arrow on the display. The focal zone is ideally positioned at (or just
below) the object the operator wants to study. More than one “focal zone” can be selected, but this can slow down the
image frame rate and can induce artefacts
Frequency Adjusting the frequency allows the operator to improve the image resolution. Frequency is the number of cycles of
acoustic waves per second. The unit is the Hertz (Hz) and one cycle per second is equal to 1 Hz; 106 cycles/second is equal
to 1 MHz. Diagnostic ultrasound has a frequency of 2–20 MHz. One should consider using higher frequencies (10–20 MHz)
when scanning superficial and low frequencies (5–10 MHz) when scanning deeper structures
Gain (overall gain control) The (overall) gain control will adjust the overall brightness of the real-time (B-mode) ultrasound image. Overall gain
control amplifies all returning signals by a constant factor regardless of the depth (in contrast to time gain control). It has a
similar effect to increasing the power. Gain is commonly expressed in decibels (dB). If the gain is increased too much, the
noise will also be amplified leading to poor image quality
Power The power button regulates the “output power” to the transducer (the intensity of the ultrasound pulses). The operator
can increase the amplitude of the electric signal to the transducer and make the returning echo signals brighter. The risk,
however, is that the acoustic exposure of the patient increases
Pulse repetition frequency (PRF) The PRF controls the rate (per second) at which pulses of sound are transmitted by the transducer
Time gain compensation (TGC) Increasing TGC (i.e., by adjusting the TGC sliders) amplifies signals from deeper structures to compensate for attenuation
causing the signals from deeper structures to be weaker than signals returning from more shallow structures. The goal of
TGC is to make the entire image look evenly bright. TGC sliders are used to adjust the gain in specific areas of the image
(near-, mid-, and far-field). The idea is to have lower gain in the near field and higher gain deeper in the image where
image quality is weaker. Most manufacturers offer a software feature that automatically optimizes the gain and overall
contrast of the image. This feature analyses the tissue in the image and attempts to provide you with the most optimized
image, but correction by the operator remains necessary
This fontanel offers visualization of the occipital horns of the Mastoid fontanel
lateral ventricles, occipital lobes, and posterior fossa structures. The mastoid fontanel is located behind the ear at the junction of the
Imaging through this fontanel improves the detection of limited temporal, occipital, and posterior parietal bones.1,15,18 The use of this
IVH and lesions in the occipital lobes and better defines posterior fontanel improves visualization of the posterior fossa (see related
fossa malformations.14 Furthermore, posterior fontanel views paper in this issue). This results in a better detection of both
allow detecting posterior cerebral artery stroke and the effects congenital and acquired posterior fossa abnormalities and in
of severe hypoglycemia. particular of cerebellar hemorrhage in preterm infants.17,19,20,26–28
Posterior fontanel CUS includes both coronal and sagittal views. The infant is positioned with the head turned to one side. The
The infant is in supine position with the head turned to one side transducer is placed behind the helix of the ear and then slightly
and slightly lifted to facilitate transducer movement (Fig. 6). moved until reproducible views are obtained. Imaging is performed
in both transverse (axial) and coronal planes. An abnormality or a
Coronal planes. The transducer is placed in the middle of the suspected abnormality can be confirmed by also scanning the
posterior fontanel such that the left half of the brain is displayed opposite side. Both the transverse and sigmoid sinuses can be
1. Interhemispheric fissure
2. Frontal lobe
3. Cavum septi pellucidic
6. Temporal lobe
7. Insula
8. Third ventricle
10.Choroid plexus
12.Lateral fissure
13.Thalamus
14.Parahippocampal gyrus
16.Occipital lobe
17 Parieto-occipital sulcus
18 Central sulcus
Fig. 4 Technique and reporting: standard coronal sections. Standard coronal sections from anterior (top left) to posterior (bottom right);
sectional planes in the scheme.
clearly visualized using the mastoid fontanel window. In many puncture. Images can be obtained in both sagittal and transverse
infants, reliable transverse cerebellar diameters can be measured planes, as described by Brennan et al.16
after visualization of both cerebellar hemispheres.
1. Interhemispheric fissure
2. Frontal lobe
3. Cavum septi pellucidi (a cavum
vergae)
4. Lateral ventricle (a frontal horn, b
atrium, c occipital horn, d temporal
horn)
5. Corpus callosum (a genu, b
splenium)
6. Temporal lobe
7. Insula, limen
8. Third ventricle
9. Basal ganglia (a) caudate nucleus
10. Choroid plexus
11. Parietal lobe
12. Lateral fissure
13. Thalamus
14. Uncus temporalis
15. Cerebellar vermis (a) and
hemisphere (b)
16. Occipital lobe
17. Parieto-occipital sulcus
18. Collicular plate
19. Calcarine sulcus
20. Base of pons
(*) Fourth ventricle
Fig. 5 Technique and reporting: standard parasagittal sections. Sections from midline (top left) to insula (bottom).
Mesencephalon
Cerebellum
Corpus callosum
Lateral fissure
Pons
Fig. 6 Technique and reporting: posterior fontanel images at 24 weeks’ GA. Posterior fontanel section, top coronal (left anterior to right
posterior), bottom sagittal and parasagittal.
v3
Mesencephalon
Pons
Vermis
Pons
Pons
Preauricular sections
Mastoid sections
Effect of myelination
T1 shortening = whitening,
T2 shortening = darkening.
Fig. 7 Technique and reporting: temporo-squamosal section. Top: sagittal section through brainstem and cerebellar vermis, compared with a
sagittal scan of an infant of 27 weeks gestation, taken though the anterior fontanel with an 8.5 MHz scanhead; far right: sagittal 7.5 MHz ultrasound
section of the area, taken through the posterior fontanel of an infant with cleidocranial dysplasia. Bottom: temporo-squamosal sections (parallel to
the cantho-meatal line, indicated in red on the top scan): the echopoor mesencephalon looks like a butterfly; the cerebral peduncles and tectal
lamina are surrounded by hyperechoic cisterns and parts of the tentorium; bright reflections in the posterior part of the brainstem coincide with
the walls of the aqueduct; in the basal cisterns, the arteries of the circle of Willis show as short, pulsating lines; term MRI sections for comparison.
whenever needed, including video sequences. Limitations that those. In the absence of sufficient safety data, apply the ALARA
influence the quality of the CUS examination (e.g., small fontanel, principle (“as-low-as-reasonably-achievable”). Furthermore, qualified
limited examination time because of the infant’s unstable technical staff should be present to service the equipment. The US
condition, or technical problems) should be mentioned. probes are made of vulnerable components and must be handled
with care. Damage to probe housing can lead to electric current
leaks. Finally, the operator should consider patient safety at all times:
SAFETY OF CUS handling critically ill newborns can be riskful, e.g., when pressure is
CUS of the newborn brain is considered non-invasive. Nevertheless, applied to the fontanel. The probes should be thoroughly cleaned,
acoustic waves can cause thermal and mechanical effects in the following the manufacturer’s instructions.
interrogated tissue. Significant heating of the brain has been
observed in neonatal animal models.41 It is unknown whether
heating of the brain affect neuronal integrity, but it seems unlikely FUTURE PERSPECTIVES
that this would occur in routine practice. State-of-the-art CUS Technological progress has led to an exponential increase in the
devices monitor and display the thermal index and mechanical computational speed of US systems and the introduction of new
index. The thermal index is the ratio of acoustic power to the power applications. “Ultrafast US” systems have been developed that
needed to raise the temperature by 1 °C in the tissue being make use of plane waves and multi-core central processing units
examined.38,39 The mechanical index represents the probability of and can process thousands of frames per second.42–44 These
cavitation, which is the formation of bubbles. It is calculated as peak systems have revolutionized the temporal resolution and sensi-
rarefactional pressure divided by the square root of the US tivity. Quantitative mapping of cerebral vascular dynamics has
frequency.38,39 The number of studies on adverse effects of US on been made possible by high-frequency imaging. Demené et al.
the developing brain with state-of-the-art US devices—especially in used ultrafast Doppler to map the vasculature dynamics of the
the most immature premature infants, those born before 28 weeks neonatal brain in vivo.43 Within a single cardiac cycle, simulta-
gestation—are still very limited.41 Therefore, clinicians would do well neous estimations of full Doppler spectra (in all pixels) could be
to weigh risk against benefit. Users of US devices should be aware obtained. Tanter et al. used ultrafast imaging to make “functional”
about the biophysical mechanisms and how US settings effect US images of the rat brain.45 The rat whiskers were stimulated and
5
Department of Neonatology, Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, Barcelona, Spain. 6Catholic University of the Sacred Heart, A. Gemelli Hospital, Rome, Italy.
7
Department of Women’s and Children’s Health, Karolinska University Hospital, Karolinska Insitute, Stockholm, Sweden. 8Department of Neonatology, La Paz University Hospital,
Madrid, Spain. 9Department of Neonatology, Quironsalud Madrid University Hospital and Biomedical Research Foundation, La Paz University Hospital Madrid, Madrid, Spain.
10
Service de néonatologie et de réanimation néonatale, Hospices Civils de Lyon, Université Claude Bernard Lyon, Lyon, France. 11Department of Clinical Sciences and Community
Health, University of Milan, Milan, Italy. 12Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico NICU, Milan, Italy. 13Department of Neonatology, Erasmus Medical Center
University, Sophia Children’s Hospital, Rotterdam, The Netherlands. 14Department of Neonatology, ZNA Middelheim, Antwerp, Belgium. 15Department of Rehabilitation and
Physical Therapy, Gent University Hospital, Gent, Belgium. 16Neonatal Intensive Care Unit, Istituto Giannina Gaslini, Via Gaslini 5, 16148 Genoa, Italy. 17Department of Paediatrics,
Medical Sciences Division, Newborn Services, University of Oxford, Oxford, UK.