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16 Current Pediatric Reviews, 2014, 10, 16-27

Cranial Ultrasound - Optimizing Utility in the NICU

Gerda van Wezel-Meijler1and Linda S de Vries2 *

1

Department of Neonatology, Isala Hospital, Zwolle, the Netherlands;

2

Department of Neonatology. WilhelminaChildrens Hospital, University Medical Center Utrecht, The Netherlands

Abstract:Cranial ultrasonography (cUS) is a reliable tool to detect the most frequently occurring congenital and acquiredbrain abnormalities in full-term and preterm neonates.

Appropriate equipment, including a dedicated ultrasound machine and appropriately sized transducers with special set-

tings for cUS of the newborn brain, and ample experience of the ultrasonographist are required to obtain optimal image

quality. When, in addition, supplemental acoustic windows are used whenever indicated and cUS imaging is performed

from admission throughout the neonatal period, the majority of the lesions will be diagnosed with information on timing

and evolution of brain injury and on ongoing brain maturation. For exact determination of site and extent of lesions, for

detection of lesions that (largely or partially) remain beyond the scope of cUS and for depiction of myelination, a single,

well timed MRI examination is invaluable in many high risk neonates. However, as cUS enables bedside, serial imaging it

should be used as the primary brain imaging modality in high risk neonates.

Keywords:Neonate, brain, cranial ultrasound, imaging.

1. INTRODUCTION

Although cranial ultrasound (cUS) is still the mostreadily available and widely used imaging technique tostudy the neonatal brain, concerns have been raised thatcUS is not able to detect subtle white matter abnormalitiesin the preterm infant [1-4] and that it is not always reliablefor detection of hemorrhagic-ischemic lesions in the terminfant [5,6]. Neonatal cUS has now been used for 30 yearsand has moved from scans through the temporal bone tohigh resolution ultrasound using different acoustic win-dows [7]. Sequential studies performed in the eighties in

infants with germinal matrix-intraventricular (GMH-IVH)and parenchymal hemorrhage (hemorrhagic periventricularinfarction (HPI)), post-hemorrhagic ventricular dilatation(PHVD) and cystic periventricular leukomalacia (PVL)have been a tremendous help in our understanding of riskfactors and helped to guide management and predictneurodevelopmental outcome in those with the most severelesions.

In the full-term infant presenting with hypoxicischemicencephalopathy (HIE), cUS is often considered of limitedvalue in detecting lesions or predicting outcome [5]. TheAmerican Academy of Neurology recommended that in en-cephalopathic term infants a CT should be performed to de-

tect hemorrhagic lesions and if findings are inconclusive,MRI should be performed between days 2 and 8 to assess thelocation and extent of the injury [8]. They did not suggest theuse of cUS in HIE.

Although it is not possible to give a complete overviewon the ample possibilities of cUS, in this review we discuss

*Address correspondence to this author at the Dept of Neonatology, KE04.123.1, Wilhelmina Childrens Hospital, UMCU, Utrecht, PO Box 85090,3508 AB Utrecht, The Netherlands; Tel: 31887554545;/Fax: 31887555320;E-mail: [email protected]

how and when to perform cUS. We will focus on white matter (WM) injury and GMH-IVH, frequently encountered inthe preterm neonate. In addition, some other abnormalitieswhich can be detected by cUS both in the preterm and full-term neonate, are described. Finally, attention is paid to thelimitations of cUS.

2. WHY AND WHEN TO PERFORM cUS?

The question is now sometimes raised why cUS shouldbe performed at all. The American Academy of Neurology

reviewed neuro-imaging strategies for evaluating pretermand encephalopathic term born infants in 2001 and suggestedthat in preterm infants

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Cranial Ultrasound - Optimizing Utility in the NICU Current Pediatric Reviews, 2014,Vol. 10, No. 1 1

hours-days after the onset, which is often clinically silent.Once the diagnosis is made, the evolution of the lesion canonly be assessed, when sequential imaging is performed. Ininfants with a GMH-IVH this will help to timely recognisethe onset of PHVD, which may help to start intervention atan appropriate point in time [12]. In the preterm infant withincreased echogenicity of the WM, only sequential imagingwill be able to show whether and when cystic evolution will

occur [13]. While extensive cystic-PVL has become lesscommon, localised cystic-PVL can still occur [14, 15]. Thesesmaller cystic lesions tend to occur later (3-6 weeks after theonset) and to resolve within several weeks. In more than50% of the infants with localised cystic-PVL, cysts were nolonger seen at term equivalent age (TEA) and in most, butnot all VM was found instead [16]. Even when doing a sin-gle MRI at TEA, the cystic phase may have passed and adiagnosis of c-PVL may have been missed. In the majorityof preterm infants with increased echogenicity of the WM,the echogenicity will resolve without cystic evolution, whileincreased echogenicity of longer duration has been shown tobe associated with later suboptimal neurodevelopmental out-come [17, 18].

It is acknowledged that the onset of cystic-PVL may oc-cur beyond the immediate neonatal period (late onset PVL),for instance following late onset sepsis or necrotising entero-colitis. It is therefore recommended to increase the numberof cUS examinations in any infant, who shows an acute dete-rioration [19].

The majority of the infants will however not developcystic lesions, and the periventricular echogenicity will even-tually resolve. These subtle WM lesions are more reliablyevaluated using MRI [1-4, 20, 21].

Performing cUS at 36-40 weeks postmenstrual age canshow:

Cysts in regression, within the spectrum of extensivec-PVL.

Cysts within the spectrum of late onset c-PVL.

Ex-vacuo VM, following WM disease, often associ-ated with increased width of the subarachnoid spaceand widening of the interhemispheric fissure [22].

VM due to PHVD following a GMH-IVH.

Cystic phase of HPI.

Cystic phase of focal arterial infarction, usually withinthe territory of the middle cerebral artery.

At present scanning protocols vary considerably betweendifferent neonatal units. Recently published guidelines appear to be useful, provided that the number of cUS examinations is increased when lesions are recognised or when theclinical situation of the infant deteriorates [7, 23-25] (Table1). A pre-discharge cUS is also highly recommended.

3. THE STANDARD CRANIAL ULTRASOUND PROCEDURE

For standard cUS procedures the anterior fontanel (AF) isused as the main acoustic window. A well-fitted transduceris essential and the scan frequency is set at 7.5-8MHz.

Ultrasound Machine

Most modern ultrasound systems are suitable for cUS ofthe newborn infant. Image quality largely depends on thesettings and the transducer(s) used, and on the experienceand skills of the ultrasonographer. It is recommended to havespecial software for neonatal cUS installed. A standard cUSpreset (including gain, transducer frequency, depth and

focus) can then be applied, enabling good quality images inmost neonates, while in some (slight) adaptations need to bedone. The gain is adjusted in order to see the highly echo-genic skull without hindering image quality of brain structures and enabling good contrast between the separate brainstructures.

Images should be stored digitally, enabling off-line as-sessments and measurements and easy exchange of information.

Transducers and Scan Frequency

The transducers used for cUS should fit (almost) per-fectly on the AF. If the footprint is too large, the contact be-tween the transducer and the fontanel is suboptimal, beingdisadvantageous for image quality. If the footprint is toosmall, the acoustic window will not be optimally used, de-creasing the diagnostic ability of cUS. For details on suitabletransducers see refs. 24 and 25 [24, 25].

The standard transducer frequency for neonatal cUS i7.5 - 8MHz. This frequency enables good visualisation ofmost brain areas in most neonates. In tiny neonates and/ofor optimal visualisation of superficial structures (includingthe subdural and subarachnoid spaces, cortex, subcorticawhite matter and venous sinuses), the scan frequency shouldadditionally be increased up to 10 MHz. This will increase

Table 1. cUS Scanning Protocol for Preterm Infants [23].

Gestational age at birth (weeks)

23-26 27-29 29-32 32-35

Postnatal age at which cUS should be done day 1,2 and 3 day 1 day 1 day 1

1 week 1 week 1 week 1 week

2 weeks 2 weeks

weekly to 31 weeks weekly to 31 weeks 3 weeks 3 weeks

alternating weeks to 36 weeks at 36 weeks

term term term term

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18 Current Pediatric Reviews, 2014,Vol. 10, No. 1 Wezel-Meijler and Vrie

the resolution, but in larger infants this may be at the ex-pense of penetration Fig. (1).

On the other hand, while imaging the brains of largerneonates and infants, and/or for good visualisation of deeperstructures (posterior fossa), scan frequency should addition-ally be decreased to 5MHz, enabling better penetration, butat the expense of resolution [24, 25].

Focus Points

For standard cUS examinations, it is recommended to usetwo focus points, positioned respectively above and belowthe periventricular and ventricular areas. These areas, vul-nerable for injury, especially in the preterm neonate, shouldbe optimally focused. In cases with (suspected) abnormali-ties beyond the focus points, these should be repositionedaccordingly [25]. If a small structure or abnormality needs tobe visualised, alternatively one focus point can be used, aim-ing at that specific area.

Scan Procedure

While performing a standard cUS examination, the wholebrain is scanned in 2 planes (coronal and sagittal), from re-spectively frontal to occipital and right to left. Coronalplanes are obtained by positioning the transducer in the mid-

dle of the anterior fontanel with the marker in the right corner, pointing towards the right ear. The transducer is thenmoved and angled forwards and backwards. To obtain thesagittal planes, the transducer is subsequently rotated 90the marker pointing towards the infants face. It is thenmoved and angled, from the middle to respectively the righand the left. At least six standard coronal planes and fivestandard sagittal planes are recorded and digitally saved. In

addition, images are recorded of each (suspected) abnormality.

For the standard coronal and sagittal planes and the brainstructures visualised in these planes see ref. 24 [24].

4. ADVANCED CRANIAL ULTRASONOGRAPHYTHE SUPPLEMENTAL ACOUSTIC WINDOWS.

When using the AF as an acoustic window and optimacUS settings, good quality images can be obtained from thesupratentorial structures, including the ventricular systemperiventricular WM, basal ganglia and thalami and the cortexand subcortical WM. However, the brain stem and posteriofossa structures, being further away from the transducer, wilnot be optimally visualised. Using the supplemental acousticwindows, i.e. the temporal windows, posterior fontanel (PF)and mastoid fontanels (MF), the transducer is positionedcloser to these structures, enabling better visualisation [7,2324, 25 - 27].

Posterior Fontanel

The PF is located at the junction of the lambdoid andsagittal sutures. This fontanel can easily be palpated inneonates and young infants, by following the sagittal sutureposter iorly from the AF. The transducer is positioned in themiddle of the PF, horizontally with the marker pointingtowards the right ear to obtain coronal planes and vertically, the marker pointing towards the cranium, for(para)sagittal planes. The PF allows good visualisation othe occipital horns of the lateral ventricles, the occipitaparenchyma, the tentorium and cerebellum. As the occipitahorns do not contain choroid plexus, echogenicity seen inthis part of the lateral ventricles is highly suspect for intra-ventricular hemorrhage Fig. (2).

Temporal Windows

The temporal windows are located above the ears. Positioning the (smallest) transducer approximately 1cm aboveand anterior to the external meatus, the marker horizontallya transverse view is obtained from the mesencephalon, brain

stem, circle of Willis and upper cerebellum. In this planeDoppler flow measurements can be performed in the circleof Willis. Image quality depends on bony thickness and thuson age at scanning.

Mastoid Fontanels

The MF, located at the junction of the temporal, occipitaand posterior parietal bones, enable detailed visualisation othe posterior fossa, including the cerebellum, 4th ventricleand cisterna magna. We use these fontanels routinely to detect congenital and acquired abnormalities of the cerebellumhemorrhage in the 4

thventricle (mostly being an extension o

Fig. (1). Coronal cUS scans performed with 10 MHz transducer

frequency in (a) very preterm infant (gestational age 25 weeks),

showing details of the cortex, subcortical WM and periventricular

WM, with a line of increased echogenicity, indicative of migrating

glial cells (arrow) and (b) a full-term infant with lissencephaly.

While the lack of sulci is normal for 25 wks GA, this finding is

suggestive of lissencephaly in a full-term infant.

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intraventricular hemorrhage) and subdural hemorrhagearound the cerebellum [24, 25, 28].

The (smallest) transducer should be placed behind theear, while gently bending the pinna forward. With the

marker horizontally, pointing towards the face, axial planesare obtained and when the transducer is rotated 90upward,pointing towards the cranium, coronal planes are obtained.

5. GERMINAL MATRIX-INTRAVENTRICULARHEMORRHAGE (GMH-IVH)

GMH-IVH is relatively easy to recognise with cUS andgives better interobserver agreement as well as correlationwith MRI than lesions involving the WM [29]. Small intra-ventricular hemorrhages may be difficult to diagnose reliablyand using the posterior fossa as an additional acoustic win-dow may aid in confirming the presence of blood within the

ventricular system [27]. The choroid plexus may be veryprominent in the immature infant, and this may lead to aninappropriate diagnosis of an IVH. A germinal matrix hem-orrhage at sites different from the caudate head, for instancein the temporal region may remain unrecognised and onlyvisualised with MRI.

Almost all hemorrhages will have developed by the endof the first week after birth and many develop within the firsthours after birth [14, 30]. Some are already present at birthand seen on the admission cUS examination. Only about10% of the GMH-IVH occurs beyond the end of the first

week. Progression from GMH-IVH to HPI can occur Fig(3). This is most likely related to impaired venous drainageof the medullary veins in the white matter with obstruction athe site of the germinal matrix [30, 31]. It is usually unilat-

eral, triangular in shape, with the apex at the outer border ofthe lateral ventricle and associated with a moderate to largeipsilateral GMH-IVH [31, 32]. HPI accounts for 3-15% oall GMH-IVH [13, 14, 30, 33]. Detailed studies by Dudink eal. have shown that it is possible to identify the veins thatwere involved in the parenchymal injury [34]. A proposawas made by Bassan et al. to grade the severity of thisparenchymal lesion, taking the extent of the lesion, the presence of a contralateral parenchymal lesion and also the presence of a midline shift into account. The grading system alsohelped to predict neurodevelopmental outcome at 2 years oage [35, 36].

Once the diagnosis of a GMH-IVH has been made, careshould be taken to assess whether there is involvement of theWM and/or the cerebellum. When the GMH-IVH is largethere is a risk of developing PHVD, which tends to occurduring the second week after the onset of the hemorrhageSequential cUS is then required and measurements of theventricular index, anterior horn width and thalamo-occipitadistance should be made, using available graphs [37, 3838a]. A midline view is used to assess enlargement of thethird and fourth ventricle, a discrepancy between these twomay be suggestive of impaired flow across the aqueductMeasurement of the ventricular index (VI) and anterior hornwidth before and after a lumbar puncture will help to asses

Fig. (2).Preterm infant, GA 26 weeks, who developed PHVD. Coronal view through the anterior fontanel and parasagittal view through the

posterior fontanel. Note discrepancy between dilatation of frontal and occipital horns. The remains of the clot are clearly seen, when in-sonated through the posterior fontanel.

Fig. (3).Preterm infant, gestational age 27 weeks. cUS performed on day 1, day 4 and day 5, coronal views showing a normal cUS on admis-

sion, with subsequent development of an IVH and later evolution into a HPI.

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whether PHVD is communicating or not. When PHVD issevere, assessment of the periventricular WM is impairedand MRI may be required to fully assess associated WMinjury.

6. WHITE MATTER (WM) INJURY

Diagnosing WM lesions using cUS is more of a chal-

lenge than diagnosing GMH-IVH. A good interobserveragreement was only shown for cystic lesions [29]. Moresubtle injury to the WM is more difficult to diagnose, moresubjective and both machine and user dependent with a low(40-50%) sensitivity, when MRI is taken as the gold standard[1-4, 20, 21]. In addition, it is important to realise that, incontrast to GMH-IVH which mostly occur within the firstdays of life, WM injury may develop throughout the neo-natal period [19].

Several markers have been suggested to be useful whenassessing changes in echogenicity of the WM:

Echogenicity equal to or higher than the echogenicityof the choroid plexus [39].

Inhomogeneous echogenicity, suggestive of punctateWM lesions (PWML) on MRI [40, 41].

Echogenicity with a duration of more than 10-14 days[17, 18, 39].

Echogenicity followed by VM.

Once again the value of cUS comes from sequential im-aging, showing the duration of the echogenicity and in somecases the evolution to more echogenic and/or inhomogene-ous echogenicity or to cystic lesions Fig. (4). The moreextensive cysts tend to occur within 2-3 weeks following aninsult, while the more localised cystic lesions may take as

long as 3-6 weeks to develop [13, 16]. As there is a rapidturnover in the neonatal intensive care unit, many infantswill be discharged before the echogenicity has had eithetime to resolve or evolve into cysts. When the infants areseen again at TEA, extensive cysts will usually still be pres-ent, although often already regressing in size and numberThe localised cysts tend to have resolved, with VM presenting as a sequel to injury to the WM. Besides the VM, widen

ing of the subarachnoid space and widening of the inter-hemispheric fissure can be seen [22].

7. ULTRASOUND IMAGING OF THE POSTERIORFOSSA

The cerebellum can be visualised when using the AF asan acoustic window. In the midsagittal plane the vermis, 4 th

ventricle and cisterna magna are easily recognized, while inthe 2ndand 4thparasagittal planes the right, respectively lefhemisphere will be depicted. Between the 4th and 5thcoronal planes both hemispheres and vermis are visualised [24]However, as this infratentorial structure is further awayfrom the transducer than the cerebral hemispheres, details

are lost when only the AF is used. In addition, the echo-genic tentorium hampers proper visualization. Using theMF will enable (early) detection of hemorrhage in the cerebellum Fig. (5), 4

th ventricle and cisterna magna, and ocongenital abnormalities [25, 28, 42-43a]. In addition, inneonates with metabolic disease, abnormalities (such acystic lesions and cerebellar hypoplasia and dysplasia) maybe found [10, 43a, 44]. We sometimes encounter hypoxic-ischemic changes in the cerebellum in full term neonateswith HIE [43a] Fig. (6).

Therefore, it is recommended to additionally use the MFin the following circumstances:

Fig. (4).Three different preterm infants, showing increased echogenicity, PVL grade I (a, coronal and b, parasagittal views), localised cystic

PVL (grade II) (c) and extensive c-PVL (grade III) (d).

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Very preterm birth (gestational age ! 30 weeks), atleast once in the first week of life

Intraventricular hemorrhage, regardless of gestationalage

Abnormal echogenicity or echogenic lesions in theposterior fossa area as seen through the AF

Ventricular dilatation

(Suspected) congenital malformations of the centralnervous system

(Suspected) metabolic disease

Perinatal asphyxia with hypoxic-ischemic changes inthe supratentorial brain structures

Posterior Fossa Hemorrhage

There is increased awareness that cerebellar hemorrhagemay complicate preterm birth, especially in extremely lowbirth weight infants [28, 46-47a]. Hemorrhage in and/oraround the cerebellum may lead to disruption of cerebellargrowth and development and to serious neurological dis-

ability [28, 45, 47-50]. Early detection is of importance forprognostication and optimal counselling and support of the

patients and their families. Hemorrhage in the cerebellumand the 4

thventricle can be detected with cUS [25, 28, 42

43, 46]. While scanning through the AF, irregular echoge-nicity or a more or less circumscript echogenic lesion may beseen in the vermis and/or hemispheres. Through the MFhemorrhages are usually better recognized as echogenic lesion(s). Sometimes a (mild) change in echogenicity ohomogeneity or absence of the normal cerebellar structure

may lead to the diagnosis (see Fig. (5)).In our experiencesmall, punctate cerebellar hemorrhages are overlooked withcUS [28].

Congenital Malformations

When the MF is additionally used as acoustic windowcongenital malformations of the posterior fossa, includingarachnoid cysts and the spectrum of the Dandy Walker mal-formations can be recognised. These malformations arecharacterised by complete or partial agenesis of the cerebellar vermis, dilatation of the 4

th ventricle and/or cisterna

magna and enlargement of the posterior fossa with elevatedtentorium [51-53] Fig. (7). In neonates with neural tubedefects, the Chiari malformation (downward displacement othe upper cerebellum, medulla and 4thventricle) may be recognised [51, 53].

Fig. (5).Coronal (a) and axial (b) cUS scans through MF in very preterm neonate (gestational age 26 weeks), showing cerebellar hemor-

rhage (arrows).

Fig. (6).a) Coronal cUS through MF in full-term neonate with severe HIE after massive feto maternal transfusion, showing increased echo-

genicity of the cerebellar hemispheres with loss of normal structures. (b) cUS scans of normal appearing cerebellum in near term infant (ges-

tational age 36 !weeks) for comparison.

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8. CRANIAL ULTRASONOGRAPHY IN THE FULL-TERM INFANT

Although MRI is superior to cUS when dealing with afull-term infant with HIE, there is an important role for cUSin this group of infants as well. First of all, a cUS examin-ation performed as part of the admission procedure, will al-

low to help with timing of the insult and may sometimesdetect unexpected lesions, which point in the direction ofunderlying problems (metabolic disorder, congenital anoma-lies) (SeeFig. (1)).

Two main patterns of injury can be found in the full-terminfant with HIE:

1)Predominant injury to the deep grey matter tends tooccur following a sentinel event. In these infants cUS tendsto be normal on admission and areas of increased echoge-

nicity usually take 24 -72 hours to develop [54] Fig. (8)Increased echogenicity is first seen in the thalami and may insevere cases subsequently also appear in the basal ganglialeading to the so called four column appearance with a lineof lower echogenicity of the PLIC in between. This appearance is strongly associated with a poor outcome, similar toan inversed signal on MRI [55].

2) The other common pattern of injury, the watershedpattern may be seen as increased echogenicity in the watershed regions. This injury pattern is more difficult to recognise with cUS as the lesions occur at the convexity of thebrain and sometimes only in the posterior regions. Using a10MHz rather than a 7.5 MHz transducer may help to detecthis type of injury and recognition will be easier when thelesions are more extensive.

Fig. (7).(a, b) Preterm infant, gestational age 31 3/7 weeks, with antenatal diagnosis of Dandy-Walker malformation; cUS scans through AF

show a small vermis which is rotated upwards. (c, d) cUS images show normal cerebellum in preterm neonate, gestational age 32 weeks.

Fig. (8).Coronal (a) and parasagittal (b) cUS scans in full-term neonate with severe HIE, showing increased echogenicity of the basal gan-

glia and thalami. A line of lower echogenicity, representing the PLIC, can be recognised in between.

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Two other forms of brain injury, mostly occurring in(near) term neonates may be detected with cUS, being arte-rial infarction and sinovenous thrombosis.

3) Arterial infarction . Although the experienced ultra-sonographer will detect most of these lesions, especially ifclinical symptoms, such as hemiconvulsions and/or asym-

metric tone or reflexes are present, MRI is superior to cUSfor the detection of arterial infarction. Smaller cortical in-farcts or infarction in the territory of the posterior cerebralartery may not be recognised by cUS. A vague area of in-creased echogenicity, asymmetry in echogenicity betweenthe two hemispheres and/or increased echogenicity aroundthe Sylvian fissure may lead to the diagnosis, but this is usu-ally not immediately apparent Fig. (9). By the end of thefirst week the increase in echogenicity will become moreobvious and will sometimes be wedge shaped with a lineardemarcation line [6].

4)Sinovenous thrombosisis probably more common thanreported, but not easily detected with ultrasound. A sinoven-ous thrombosis should however always be suspected when a

full-term infant presents with seizures in the presence of anIVH on cUS and especially when a unilateral thalamic hem-orrhage is present as well [56]. Doppler ultrasound may fur-ther support the diagnosis, but a confirmation with MRI-MRV is required to confirm the diagnosis and establish theextent of the thrombosis [57].

9. MISCELLANEOUS

cUS may also provide useful information in the pretermand full-term infant who will be admitted for neonatal en-

cephalopathy and/or seizures but without a history of perinatal asphyxia. cUS performed on admission may help tomake an appropriate diagnosis.

cUS is not only useful to detect hypoxic-ischemic orhemorrhagic injury, but may also detect congenital malformations and injury due to infection of the central nervou

system or to metabolic disorders.

Infections

The presence of a congenital infection, especially CMVis often suggested by cUS findings, such as germinolyticcysts, subependymal pseudocysts and lenticulostriate vasculopathy Fig. (10). Bilateral occipital cysts are highly suggestive for CMV while temporal horn cysts are also seen incongenital rubella infection [11]. Increased echogenicity inthe WM in an infant presenting with neonatal seizures andsometimes a rash and/or fever, can be suggestive of an enterovirus or parechovirus infection and changes on MRI-DWI will be seen in these two entities [58, 59, 59a] Fig(11). In infants who present with a bacterial infection, eithea meningitis-ventriculitis or encephalitis, cUS abnormalitiesare common and easy to recognise. Ventricular dilatation andstrands in the ventricles as well as increased echogenicity ofthe ventricular ependyma may be seen in the milder caseswhile abscesses or rapid destruction of the WM can be seento develop in more severely affected infants Fig. (12).Infection with Citrobacter koseri is well known to be associated with abscess development. Bacillus cereus meningitis/encephalitis is rare but can destroy the WM within hoursoften not allowing time to perform MR imaging [60] (seeFig. (12)).

Fig. (10).Coronal (a) and parasagittal (b) views in a full-term infant with congenital CMV infection, showing extensive lenticulostriate vas-

culopathy and germinolytic cysts.

Fig. (9).Coronal cUS scans in full-term neonate presenting with seizures, showing asymmetry of the sylvian fissure (arrow in a) and asym-

metric cortical folding (arrow in b). MRI confirmed cUS diagnosis of left sided MCA infarction, the DWI showing diffusion restriction.

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Fig. (11).Preterm neonate (gestational age 36 weeks) with enterovirus sepsis and encephalitis. Coronal (a) and parasagittal (b) cUS scan

show patchy, inhomogeneously increased echogenicty of the periventricular and subcortical WM. T2 weighted MR image ( c) shows abnor

mal signal intensity in the WM. The DWI (d) showed restricted diffusion in the WM and corpus callosum and also in the corticospinal tracts

hippocampi and cerebellum (not shown).

Fig (12).Preterm infant, gestational age 30 weeks, who developed Bacillus Cereus septicaemia with rapid liquefaction of the white matter

Echogenicity seen on coronal view (a), liquefaction on parasagittal view (b).

Metabolic DisordersIn an infant, presenting with neonatal encephalopathy in

the absence of a history of perinatal asphyxia, a metabolicdisorder may be considered. Several cUS findings may helpin the diagnosis as was reviewed by Leijser et al.[10]. Ger-minolytic cysts in a floppy infant with a large anterior fonta-nel, can help with the diagnosis of a peroxisomal disorderFig. (13), but are for instance also seen in mitochondrialdisorders. It is important to realise that these cysts are bettervisualised with cUS than MRI [14]. A hypoplastic corpuscallosum in an encephalopathic infant with hiccups wouldhelp to suggest a diagnosis of non-ketotic hyperglycinaemia.

Altogether a variety of cUS abnormalities can be seen ininfants with metabolic disorders, with germinolytic cystslenticulostriate vasculopathy, mild VM, increased echogenicity of the WM being most common findings [10].

10. LIMITATIONS OF cUS AND INDICATIONS FORMRI

Despite the numerous advantages, cUS has limitations, assome abnormalities, including some that may be of importance for neurological outcome, may be missed or overlooked. The brains convexity is not well visualised; (small)arterial cortical infarctions and watershed lesions may be

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overlooked, especially in the first days after the event; hypo-glycemic parenchymal injury involving the occipital lobes isoften not recognized unless cUS is performed through theposterior fontanel and punctate lesions may be suspected butare better detected with MRI [1, 6, 21, 28, 61] . Some lesionsresulting from infection, such as (micro) abscesses and en-cephalitis may not be optimally recognized by cUS [11]. Involvement of the (posterior limb of the) internal capsula inlesions, of major importance for neurological outcome, can-not be determined with certainty by cUS [55, 62]. However,the PLIC can be reliably recognised as a rim of low echoge-nicity on cUS in infants with HIE and moderate-severe basalganglia injury(See Fig. (8)).

MRI, if well timed, performed under optimal circum-stances and while using special neonatal scan protocols (in-cluding high field strengths, specially adapted sequences,thin slices without or with small gaps), is invaluable to de-termine the exact origin, extent and location of lesions, todetect lesions that are not well detected by cUS and to assess

myelination [1- 4, 6, 20, 21, 28, 55, 61, 62, 63].We thereforerecommend to perform MRI examinations for the followingindications:

Perinatal asphyxia, HIE stages II or III [64]

Full-term infant presenting with neonatal seizures

Neurological symptoms, insufficiently explained bycUS findings

(Suspected) supratentorial parenchymal abnormalitiesas seen by cUS

(Suspected) infratentorial abnormalities as seen bycUS

(Suspected) congenital or acquired infections of the

central nervous system

(Suspected) congenital malformations of the centralnervous system

(Suspected) subdural or subarachnoid hemorrhage

Hypoglycaemia in the presence of seizures

Metabolic disease

Post hemorrhagic ventricular dilatation (reliable as-sessment of the WM)

Prematurity, gestational age < 30 weeks (reliable de-tection of WM and cerebellar injury)

11. SUMMARY AND CONCLUSIONS

cUS is an excellent modality to visualise the brain duringthe neonatal period and thereafter until closure of the fontanels. It is performed at the bedside, enables routine screening for abnormalities in high risk populations, can follow

brain growth and maturation and the evolution of intracranialesions. Optimising cUS is achieved by

The use of appropriate equipment with optimised set-tings

The use of supplemental acoustic windows when indicated

Performing sequential examinations

When the criteria mentioned above are met, the experi-enced ultrasonographer can detect the most frequently occurring congenital and acquired brain abnormalities, bothin full-term and preterm neonates. However, cUS is nosuitable to determine the exact origin, location and exten

of lesions, some abnormalities may be missed or overlooked and myelination can not be depicted. As imagequality of both ultrasound and MRI is superior to that oCT for imaging the neonatal brain and both modalities aremuch safer than CT, we feel that the use of CT of the brainin neonates should be restricted to acute situations, where arapid diagnosis may lead to neurosurgical intervention. Asingle, well-timed MRI examination, performed under optimal circumstances is indicated in most neonates withneurological symptoms or (suspected) cUS abnormalitiesand in neonates born very prematurely.

CONFLICT OF INTEREST

The authors confirm that this article content has no con-flict of interest.

ACKNOWLEDGEMENTS

Declared none.

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Received: July 24, 2012 Revised: March 23, 2013 Accepted: September 04, 201

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