magnetic resonance imaging of the newborn brain - navigation bar new

Current Paediatrics (2002) 12, 401^413�c 2002 Elsevier Science Ltddoi:10.1054/ycupe.0318, available online at http://www.idealibrary.com on

Magnetic resonance imaging of the newborn brainSerena J.Counsell andMary A.Rutherford

Robert SteinerMRUnit, Imaging SciencesDepartment,MRCClinical SciencesCentre,FacultyofMedicine, Imperial College,HammersmithCampus,Du Cane Road, LondonW12 0HS,UK

KEYWORDSchronic pelvic pain,conscious painmapping,pelvic congestion, nerveentrapment, LUNA,trigger points, adhesions

Summary Magnetic resonance (MR) is an ideal tool for imaging the neonatal brain,although adaptationsmayneed to bemade to bothhardware and sequences.It is usefulfor assessingmanydiseasesintheimmaturebrainincludinghypoxic^ischaemicencepha-lopathy, infarction and infection, examples of which are given in this review.Athoroughknowledge of the normal MR imaging (MRI) appearances atdi¡erentgestations aswellas the variation with di¡erent sequences is necessary for correct scan interpretation.The imagingappearance of lesions inthenewbornbrain depends onthe timingand nat-ureoftheinsult andthepulse sequenceused.Techniques suchasdi¡usion-weightedima-ging provide important early information in ischaemic lesions. Quantitative MRItechniques, such as three-dimensionalvolumetricMRI, canbeusedtoprovideobjectiveassessmentof brain development in bothhealth and disease.�c 2002 Elsevier Science Ltd

PRACTICEPOINTS

K MR imaging is useful for assessing many diseases inthe neonatal and preterm brain including hypoxic^ischaemic encephalopathy, infarction and infection

K The imaging appearance of lesions in the newbornbrain depends on the timing of the insult and thepulse sequence used

K A thorough knowledge of the normal appearancesat di¡erent gestations as well as the variation withdi¡erent sequences is necessary

K QuantitativeMR imaging techniques, such as three-dimensional volumetric MRI, can be used to provideobjective assessment of development and diseaseprogression

INTRODUCTIONMagnetic resonance (MR) imaging is non-invasive andnon-ionizing and provides excellent soft tissue di¡eren-tiation, making it themodality of choice for investigatingnumerous diseases of the brain. Its use in adults isestablished, and an increasing number of centres arenow using it to investigate the newborn brain.

Correspondence to MAR.Tel.: +44 20 8383 3298; Fax: +44 20 83833038; E-mail: [email protected]

MRPULSESEQUENCES

The termneonatal brain contains approximately 92^95%water and this decreases over the ¢rst 2 years of life toadult values of 80^85%. The high water content of theneonatal brain is associated with a marked increase inT1 (longitudinal) and T2 (transverse) relaxation times incomparison to adults. As a result the pulse sequencesneed tobe adjusted to allow for the di¡erentMRproper-ties of the immature brain.We routinely use aT1weighted conventional spin echo

sequence (CSE) (TR 860/TE 20ms) (TRFrepetitiontime, TEFecho time), a T2 weighted CSE (TR 2700/TE120ms) or a T2 weighted fast spin echo (FSE) sequence(TR 3500/TEe¡ 208ms) and an inversionrecovery (IR) se-quence (TE 3800/TI 950/TE 30ms).In addition to standard T1 and T2 weighted imaging,

which are used for qualitative image assessment, quanti-tative MR techniques are available. Three-dimensional(3D) volumetric MR imaging allows measurement ofwhole brain volume, as well as di¡erent structures suchas theventricles and cerebellum.This technique can pro-vide data to identify subtle deviations fromnormal1^3 andchange in brain size over time.4 MR imaging can also beused to assess physiology, with techniques such as di¡u-sion (DWI) and perfusion weighted imaging (PWI).DWIis able to demonstrate areas of acute infarction beforethey are visualized with conventional MR imaging. As in

402 CURRENT PAEDIATRICS

the adult patient, intravenous contrast enhancementshould always be used in cases of suspected infection.Using T1 weighted imaging, contrast enhances areaswhere there is a breakdown in the blood^brain barrier,such as someparenchymal lesions and infectedmeninges.

TIMINGTHEMRIMAGINGEXAMINATIONThe ideal time to image depends on the information re-quiredbut is often constrainedby theresources availablefor imaging sick neonates.Conventional scansperformedwithin the ¢rst 24hmay appear normal evenwhen therehas been severe perinatal injury to the brain. Early ima-ging will help to di¡erentiate antenatal fromperinatal le-sions. Perinatally acquired abnormalities ‘mature’ andbecome easier to identify by the end of the ¢rst week.For information on the exact pattern of injury a scan be-tween1and 2weeks of age is usually ideal. After 2 weeksthere may be signs of cystic breakdown and atrophy,which may make the initial pattern of injury more di⁄-cult to de¢ne.

INFANTPREPARATIONFORSCANNINGNeonates can often be scannedwithout sedation duringnatural sleep. Infants over the age of 3 months almost

Figure 1 Normal appearances of the brain atterm.Inversion recposterior limb of the internal capsule (long arrow) and in the regiweighted imaging (SE 2700/120ms).The myelin in the internal capsintensity in the region ofthe ventrolateralnuclei ofthe thalamus (sh

always require sedation and we usually use chloral hy-drate orally or via suppository. It is rarely necessary touse general anaesthesia to image a child under 2 yearsold. All neonates and infants undergoing MR scanningare monitored with ECG and pulse oximetry and a pae-diatrician is in attendance throughout. Infants who re-quire assisted ventilation can be imaged in an MRscanner providing MR compatible ventilation and moni-toring equipment is available. As with all MR examina-tions, a thorough metal check is essential beforeimaging, and particular neonatal metallic hazards needto be considered, such as Searle arterial lines, electronicname tags and portable oxygen cylinders.

MRIMAGINGOF THENORMALNEONATALBRAINIn the neonatal brain, unmyelinatedwhitematter (WM)has a low signal intensity (SI) onT1weighted images andhigh SI onT2 weighted images.Cerebrospinal £uid (CSF)is hypointense onT1weighted imaging and hyperintenseonT2 weighted imaging (Fig.1).Myelination begins at around 20weeks gestational age

(GA) and continues up to around 2 years of age. Asmye-lination proceeds, the water content of WM decreases,causing a reduction in SI onT2 weighted imaging. Thereis a corresponding increase in glycolipids, cholesteroland proteins, which causes an increase in SI on T1

overy sequence (IR 3800/30/950 ms). (a) There is high signal in theon of the ventrolateral nuclei of the thalami (short arrow). (b) T2ule has a low signal intensity (long arrow).There is also low signalort arrow).

MAGNETICRESONANCEIMAGINGOF THENEWBORNBRAIN 403

weighted imaging.5 Changes in the SI ofWMdue tomye-lination are demonstrated at di¡erent ages onT1and T2weighted imaging. T1 weighted imaging is better at de-monstrating myelination in the ¢rst 6^8 months afterbirth and T2 weighting is better between 6 and 18months.6

MRIMAGINGOF THENORMALPRETERMBRAINThe cerebral cortex is demonstrated as high SI on T1weighted imaging and low SI on T2 weighted imaging.The very premature brain has little sulcation and gyra-tion at 24 weeks GA but this rapidly evolves. On T2weighted imaging prior to 30 weeks GA, bands of low SIare visible within the cerebral WM, around the lateralventricles,7 representing glia migrating from the germ-inal matrix to the developing cerebral cortex8 (Fig. 2).Areas of extremely high SI on T2 weighted FSE imagesare visualized around the anterior and posterior hornsof the lateral ventricles between 24 and 36 weeks GA7

(Fig. 2). Histologically, these extremely high SI areas arecomprised of dense ¢bre bundles, which are less orga-nized than elsewhere in thewhitematter of the centrumsemiovale, and have a relatively low cellular density.9

The germinal matrix (GM) is visible up to around 32weeks GA as a prominent structure at the margins ofthe lateral ventricles (Fig. 2). After this age, small residualareas of germinal matrix are visualized at the anterolat-

Figure 2 Preterminfant at 26 weeksgestationT2 weighted fast sThere is a relatively smooth cortex.Low signal intensity areas of germcaudate heads (arrowhead) and in the roof of the temporal horns (periventricular white matter. (b) High ventricular level.There are losponding to cellsmigrating out fromthe germinal zones to the devel

eral angles of the lateral ventricles, adjacent to the headof the caudate nucleus and in the roof of the temporalhorns.GMis demonstrated as high SI onT1weighted ima-ging and low SI onT2 weighted imaging (Fig. 2).Myelin has been demonstrated in numerous central

structures in the very preterm brain such as the brain-stem, cerebellum and thalami.10 Myelin is not seen in thewhitematter of the cerebral hemispheres until 35 weeksGA. Quantitative MR imaging studies have demon-strated a steady increase in brain surface area and corti-cal folding1 and a reduction inT2 values in the cerebralWMwith increasing GA.11

MRIMAGINGASSESSMENTOFBRAININJURYINTERMINFANTS

Acute asphyxia

The term infant with a history suggestive of acute as-phyxia is at risk of developing hypoxicîschaemic ence-phalopathy (HIE).The term ‘neonatal encephalopathy’ isnow consideredmore appropriate as it re£ects the pro-blems in proving that a fetus has su¡ered a hypoxicîschaemic event.

Basal ganglia and thalamic lesions

Term infants that develop HIE following a well-de¢nedacute hypoxicîschaemic insult (e.g. placental abruption,

pin echo sequence (FSE 3500/208e¡ ms). (a) Low ventricular level.inalmatrix are seen in the anterior horns (long arrow), over the

short arrow).There are high signal intensity areas in the anteriorw signal intensity bands (arrows) within the white matter corre-opingcortex.There is high SI inthe periventricular whitematter.


uterine rupture) typically sustain bilateral lesions withinthe basal ganglia and thalami (BGT).12

Occasionally, severe BGT lesions are seen with lessobvious precipitating events. This may re£ect failureto recognize the severity of asphyxia or an in-dividual susceptibility to damage because of previoushypoxic^ischaemic events or an underlying metabolicor thrombotic disorder. BGT lesions that occur manyweeks before term delivery have been described follow-ing attemptedmaternal suicide.13

The BGT are susceptible to injury because they aremetabolically very active in the immature brain.14 Thechanges seen on MR imaging are thought to be second-ary to ischaemia although the SI abnormalities are suchthat they were originally described as haemorrhagic.The short T1 and T2 lesions seen as the lesions evolveare probably due to capillary proliferation and later tomineralization.9

In term infants with HIE the main sites of abnor-mality are the posterior and lateral lentiformnucleus and the ventrolateral nuclei of thalami(Fig. 3). More extensive lesions may involve all ofthe basal ganglia and medial areas of thalami (Fig. 4)and there may be spread downwards to involvethe midbrain and the dorsal aspects of the ponsand medulla (Fig. 5). Infants with such extensive lesionsusually have stage-III HIE and die within days or weeksof birth.

Figure 3 Bilateral basal ganglia (BGT) lesions. (a) Infant with stag950ms).There are several areas of veryhigh signal intensity within tfrommyelinwithin the posterior limb of the internal capsule but thethere are characteristic focal low signal intensity cysts in the postearrow).This infantdeveloped athetoid quadriplegia.

In the term infant, the most clinically useful associa-tion with BGT lesions is the SI within the posteriorlimb of the internal capsule (PLIC). In the normalbrain at term, there should be evidence of myelinin the posterior 1/3^1/2 of the PLIC (Fig. 1). Myelinationis usually ¢rst evident at around 37 weeks gestation andslightly earlier in infants born preterm. Absence of thenormal SI in infants older than 37weeksGA is often seenwith severe BGT lesions (Fig. 4) and it is able to predictthe neurodevelopmental outcome in term infants withHIE.15 Its advantage for predicting outcome is that itmay appear before abnormal SI within other areas ofthebrain.However, itmay still takeup to 48h tobecomeabnormal in some infants, and the appearances of the ab-normal PLIC can vary andmay sometimes be di⁄cult tointerpret.Additional abnormalities associated with BGT lesions

include early brain swelling, with diminished extracereb-ral spaces and slit like ventricles. Abnormal, mainly shortT1, appearances in the cortex so-called‘cortical highlight-ing’ almost always accompany signi¢cant BGT lesions atterm.The predominant sites are the central ¢ssure, theinterhemispheric ¢ssure and the insula.The depths of thecortical sulci are preferentially a¡ected (Fig. 6).The high-lighting is consistent with capillary proliferation occur-ring as a result of infarction in the deepest layers ofcortex. An abnormal SI may take several days to evolveandbe seenmost clearly during the secondweek.By this

e-IIHIE imaged at 5 d. Inversion recovery sequence (IR 3800/30/he lentiformnuclei and thalami (arrows).There is somehigh signalre is an additional parallel low signal intensity. (b) At1year of age,rior part of the putamen (long arrow) and in the thalamus (short

Figure 4 SevereBGTabnormalities. (a) Infantwithstage-IIHIEimagedat 7 d.Therearewidespreadabnormalhigh SIthroughoutthelentiformnucleiandthalami.There are additionallowsignalintensitycystic areaslaterally. (b) Infantwithstage-IIIHIEat12 dof age.Thereis abnormallowsignalintensitywithintheposteriorlimboftheinternalcapsule (arrow).There are abnormalhighsignalintensitieseitherside of the PLIC.

Figure 5 Brain stem and hippocampal abnormalities. Inver-sion recovery sequence (IR 3800/300/950ms).There are areasof abnormal high signal intensity within the mesencephalon.Thereis abnormalhigh signalintensityinthehippocampal region(arrow).There is already some dilatation of the temporalhorn ofthe lateral ventricle consistent with atrophy.This infant also haddi¡use changes throughoutthebasalganglia andthalamionima-gingand atpostmortem.


time the adjacent subcortical white matter often devel-ops abnormal SI consistent with infarction (Fig. 6).Severe BGT lesions are also associated with abnorm-

alities in the medial temporal lobe.These are not imme-diately obvious but by the end of the secondweek, thereare often de¢nite short T1areas within the hippocampalregion and dilatation of the temporal horn as a result ofadjacent tissue atrophy (Fig. 5). In some infants with se-vere BGT, there are additionalwidespread abnormalitiesin the white matter with appearance of infarction givingrise to multicystic leucomalacia (Fig. 7). In infants withHIE who develop both BGT and early white matter in-farction, there may be compounding factors that primethe white matter. These factors may include chronic orrepetitive ischaemic insults, infection or an inherent sus-ceptibility to ischaemia.The clinical outcome of the infant is dependent on the

severityof the BGT lesions. Severe BGT lesions are asso-ciatedwith a spastic ormixeddystonic/spastic quadriple-gia, secondary microcephaly and marked intellectualimpairment.There are usually persistent feeding di⁄cul-ties, which often requires a gastrostomy to avoid long-termnasogastric tube feeding.These childrenmake littledevelopmental progress and may have seizures, whichare di⁄cult to control. Early death is common, usuallyas a result of respiratory complications. In infants with acombination of BGT and multicystic leucoencephalopa-thy (Fig. 7), the neurodevelopmental outcome is deter-mined mainly by the severity of the BGT, particularlyin terms of motor impairment. Less severe BGT le-sions (Fig. 3) are associated with the development of an

Figure 6 Abnormal highlighting of the cortex. Term infantstage-IIHIE aged12 d.Inversion recovery sequence (IR 3800/30/950ms).There is cortical highlighting around the central ¢ssure(long arrow), which ismaximal atthe depths of sulci.There is ad-ditionallow signalintensityinthe adjacent subcorticalwhitemat-ter (short arrow).

Figure 7 Severe basal ganglia and white matter abnormal-ities. Inversion recovery sequence (IR 3800/30/950ms). Infantwith stage-II HIE at 8 d of age. Low signal intensity is presentthroughoutthewhitematter (long arrow) with areas of corticalhighlighting at the depths of sulci (short arrow).There is abnor-malhigh signal intensity inthe basal ganglia and thalami aswell asabnormallow signal intensitywithinthe PLIC.


athetoid quadriplegia usually with good preservation ofintellect and normal head growth.Mild BGT lesionsmaybe associatedwith late onset tremor, andmild but oftentransient abnormalities of tone.

EARLYSEIZURESWITHMINIMALDEPRESSIONOFAPGARSCORESInfants who present with seizures but in whom Apgarscores were near normal show a variety of pathologies.16

These include haemorrhagic or infarctive lesions, conge-nital or acquired infection, congenital abnormalities andmetabolic disorders.Despite the good condition at birth, these infantsmay

still have sustained a perinatal injury to the brainalthough the lesions are more likely to involve the whitematter and cortex.These abnormalities include areas ofinfarction that may be focal, multifocal, widespread orparasagittal in distribution.

Evolution of perinatally acquired infarction

Acute infarction is bestdetectedwithDWI, thenwithT2weighted images and lastly with T1 weighted images(Fig. 8). Areas of infarction show restricted di¡usion ofwater molecules, which gives an abnormal high SI on

DWI.This is often detectable within hours of the insultand is certainly present at the time the infant comes toimaging. The abnormal high SI on DWI gradually de-creases over the ¢rst 10d while abnormal SI becomesmore obvious with conventional imaging. T2 weightedimages show abnormal high SI and a loss of the normallow SI of cortical markings, presumably due to oedemaand/or infarction of the cortex (Fig. 8). T1 weightedimages show loss of grey/whitematter di¡erentiation in-itially (Fig. 9).This loss of di¡erentiation may return dur-ing the secondweek andbecome exaggeratedre£ectingabnormal low SI within the WM and abnormal high SIwithin the cortex (Fig. 7). Breakdown and atrophy ofthe infarcted tissue may become obvious after 2 weeksand generally lasts until about 6 weeks. This pattern ofabnormal SI using the di¡erent sequences is similarwhat-ever the extent of infarction.

Parasagittal infarction in the term infant

Parasagittal infarction involves the deep WM at borderzones of major artery territories (Fig. 8). Some of theseinfants may present with ‘full blown’ HIE although theclinical history is often atypical and there may be an ab-normal antenatal history.Parasagittal lesions may occur in the presence of

severe hypoglycaemia.17,18 Infants with parasagittal

Figure 8 Parasagittal infarction. (a) T2 weighted fast spin echo sequence in an infant aged 3 d.There is loss of grey/white matterdi¡erentiation in the anterior and posterior parietal lobes. (b) This ismore obvious on di¡usionweighted imagewhere the abnormalhigh signalintensityis causedbyrestrictedmotionofwatermoleculeswithinthe acute infarcts.Thereis alsonormalhigh signalintensityfrommyelin in the PLIC andnormal signal intensitywithinthe basalganglia and thalami.

Figure 9 Middle cerebral artery infarction .Termborn infantpresenting with neonatal convulsions. Inversion recovery se-quence (IR 3800/30/850ms) aged 5 d. This shows loss of grey/white matter di¡erentiation consistent with a left-sided middlecerebral artery infarction involving the cortex andwhitematterof the posterior parietal and temporal lobe (arrows).The basalganglia, thalami and the PLICwerenormal at a lower levelinthisinfant.


infarction usually develop a secondary microcephalyalthough the neurodevelopmental outcome is often sur-prisingly good, particularly for motor function. This is

because there is usually minimal or no involvement ofthe basal ganglia and thalami. However, underlyingpathologies such as severe persistent hypoglycaemia areassociatedwithmajor cognitive problems.Large areas of haemorrhagic white matter infarction

may also be seen in infants with or without some signsof HIE.Once again the basal ganglia and thalami may bespared. These infants may show more profound meta-bolic abnormalities such as prolonged conjugated hyper-bilirubinaemia and recurrent hypoglycaemia. Theseinfants often developmarkedcognitivewith somemotorimpairment such as a mild diplegia. A search for an un-derlying metabolic disorder should be carried out butthismay not be successful.Multifocal areas of infarction that do not appear to be

in a parasagittal distribution may be secondary to infec-tion, e.g. herpes, varicella, listeria (Fig.10).Contrast en-hancement should always be used if acquired infection issuspected. Prompt detection and treatment of early le-sionsmaymodifyor preventbrain damage.Whitematterlesions may also be seen in congenitally acquired infec-tions such as cytomegalovirus (CMV) (Fig.11) or rubella.In CMV the white matter may have a persistent abnor-mal SI for years but not atrophy. The presence of sub-ependymal cysts that protrude into the ventricle arecommon in congenital infections and should always pro-voke appropriate investigations.

Focal infarction in the term infant

Perinatally acquired focal infarction, or ‘neonatal stroke’,is usually left sided and involves the territory supplied by

Figure 10 (a) Termborn infant with a history of maternal varicella infection at15 weeks gestation. Inversion recovery sequence (IR3800/30/950ms).There are areas of infarction within a mature looking brain (arrow) consistent with infarction within the late thirdtrimester. (b) Termborn infant with perinatally acquired herpes infection. Inversion recovery sequence (IR 3800/30/950ms) demon-stratingmultiple areas of whitematter and cortical infarction (arrows).Thesewere not con¢ned to the temporal regions. (c) Preterminfant at 32 weeks gestation with a history of maternal listeria just prior to delivery.T1weighted spin echo sequence (SE 860/20ms).There arebilateral abnormalities.Thelesionsontheright aremainlyhaemorrhagic (longarrow).Thereis extensiveperiventricularcystformation onthe left (short arrows).


themiddle cerebral artery (Fig. 9).Neonatal stroke is as-sociatedwith some speci¢c antenatal factors, e.g. primi-gravida, history of abdominal pain, fetal distress,instrumental delivery, but may be asymptomatic. Theclinical picture is not usually one of ‘full blown’ HIE andthe infants usually go to the postnatal ward following

delivery. It is unusual for focal arterial infarctions in theterm infant to be haemorrhagic although there may behaemorrhage in other sites of thebrain and awell-recog-nized combination is the presence of focal infarctionadjacent to an area of subdural haemorrhage. A uni-lateral lesion within the thalamus or basal ganglia may be

Figure 11 Cytomegalovirus infection. (a) Preterm infant withearly postnatally acquired cytomegalovirus infection. Imaged atterm equivalent age. Inversion recovery sequence. There is awidened caudothalamic notch (long arrow) consistent with pre-vious subependymal cysts. Subependymal cysts which areclearly visible on ultrasound are easily missed on MR imaging.Thereis additional abnormallowsignalintensitywithinthewhitematter (short arrows).

Figure 12 Thalamic haemorrhage. Term infant who pre-sented with convulsions. (a) Inversion recovery sequence (IR3800/30/850ms). There is unilateral high signal intensity in thethalamus consistent with primary haemorrhage or haemorrha-gic infarction (long arrow). (b) There is additional haemorrhagewithin the right lateralventricle (short arrow).


infarctive, particularly in themore preterm infant.19 Oc-casionally, they may be found as an additional antenatallesion in infants with neonatal stroke. They may thenhighlight an inherent predisposition to infarction eitherbecause of a thrombotic disorder or because of amater-nal embolic source.Outcome following neonatal stroke depends on the

sites involved, so that those infants that have abnormal-ities within the hemispheric white matter/cortex, theBGTand the PLIC have a high incidence of later hemiple-gia.The development of hemiplegia in childrenwith peri-natal stroke has also been associated with the presenceof factor V Leiden heterogenicity.20

Haemorrhagic lesions

Infants with seizures and normal Apgar scoresmay havesustained a haemorrhagic lesionwithin or external to thebrain.16 The SI of haemorrhage on MRI varies dependingon the site of the haemorrhage, the age of the haemor-rhage and the pulse sequence used.21Multiple small hae-

morrhagesmaybe seen in theparenchyma.Thesemaybeassociated with a period of hypoglycaemia. A more un-usual but well-recognized lesion is that of haemorrhagewithin the thalamus (Fig. 12). The aetiology of thalamichaemorrhage is obscure. Imagingmay identify associatedintraventricular haemorrhage (IVH) (Fig.12) and can helpwith dating the lesion although haemorrhage within thethalamus and the ventricle may evolve di¡erently. TheIVHmaybe severe enough to causeventricular dilatationthat requires intervention. The haemorrhage graduallyresolves to leave an atrophied thalamus. These infantsmay develop a hemiplegia and cognitive problems.Infantswith seizures and a historyof a traumatic deliv-

ery, shoulder dystocia or an expanding head may havesustained an extracerebral haemorrhage. Subdural hae-morrhage is associatedwith di⁄cult deliveries and is re-latively common in the asphyxiated infant (Fig. 13). Itoccasionally occurs secondary to a congenital clottingdisorder. Subdural haemorrhagemay also occur withoutan obvious precipitating event. In the infant who has al-ready been discharged from hospital, non-accidentalinjury needs to be considered. Subarachnoid haemor-rhage may be asymptomatic and is probably quite fre-quent following even normal deliveries. It follows thecontours of the brain and, if small, may be di⁄cult toidentify. If more extensive, it may be di⁄cult to distin-guish from subdural haemorrhage.

Figure 13 Subdural haemorrhage in an infant with stage-IIHIE, delivered by vacuum extraction following a failed attemptatforceps.T1weighted spin echo sequence (SE 860/20ms).Thereis extensive abnormal high signal intensity consistent with hae-morrhage in the subdural space over the parietal lobes (arrow-heads), in the posterior fossa and around the tentorium (longarrow).There is a small amountof intraventricularhaemorrhageinthe posteriorhorns (short arrow).

Figure 14 Sagittal sinus thrombosis.T2 weighted (FSE 3000/208e¡ ms) image in an infant with stage-IIHIE and a high haema-tocrit.There aremultiple areas of haemorrhagic infarctioninthecortex and subcortical white matter (arrows). Imaging of thesagittal sinuswas consistentwiththrombosis.


Sinus thrombosis occurs due to trauma, sepsis, cardiacfailure, dehydration or an increased haematocrit. Sinusthrombosis may be di⁄cult to con¢rm.Normally, the si-nuses are depicted as low signal onT1weighted MRI, dueto £owing blood. This is dependent on the position ofblood £ow in each slice. In sagittal sinus thrombosis, theSI is not pathognomonic. In thrombosis, the sinus is typi-cally high SI onT1weighted images and low signal onT2weightedimages on all slices and in all planes.T1weightedsagittal images from a 3D volume setwith an unselectedradiofrequency pulse which is largely £ow independentmay be useful. Contrast enhancement may help to con-¢rm a patent sinus or demonstrate a ¢lling defect. Sinusthrombosis is associated with speci¢c patterns of par-enchymal injury, including haemorrhagic lesions in thecortex and white matter (Fig. 14). Straight sinus throm-bosis is associated with lesions within the basal gangliaand thalami.

Metabolic disorders

Neonateswith early seizures but apparently normal Ap-gar scores may have a neurometabolic disorder, such asnon-ketotic hyperglycinaemia or Zellweger’s syndrome.Imaging may be normal, show delayedmyelination or beassociated congenital malformations such as agenesis of

the corpus callosum and corticalmigration defects. Bilat-eral BGT lesions may also be seen in certain metabolicdisorders that present in the neonatal period, e.g. Leigh’sdisease. These infants may be di¡erentiated from thosewith HIE by the evolution of their clinical signs but thereis often overlap, and so all infants with HIE or thosewithbasal ganglia lesions should have a full metabolic screenand a congenital infection screen. In neonates with ker-nicterus abnormal signal intensity within the globus palli-dus and subthalamic nuclei may be relatively subtle forthe ¢rst fewmonths (Fig.15).

MRIASSESSMENTOFBRAININJURYINPRETERMINFANTSThe developingbrain is highly susceptible to injury includ-ing periventricular leucomalacia (PVL), intraventricularhaemorrhage/germinal layer haemorrhage (IVH/GLH)and parenchymal haemorrhagic infarction. The majorityof preterm infants demonstrate some abnormality onbrainMRimagingin the earlyneonatalperiod.8Addition-ally, quantitative MRI has revealed delayedmyelination inadolescents whowere born preterm22 and reduced cor-tical folding1 in the preterm brain at term equivalent agecomparedwith termborn infants.21

Figure 15 Kernicterus. Term born infant with hyperbilirubi-naemia. Neonatal imaging was equivocal with some increasedsignalintensitywithintheglobuspallidumonT1weightedimaging,but at11months of age there are obvious abnormal areas of in-creased signal intensityontheT2 weighted images (arrows).

Figure 16 Germinal matrix haemorrhage. Preterm infantborn at 26 weeksgestationT2 weighted fast spin echo sequence(FSE 3000/208e¡ ms). The germinal matrix haemorrhages areseen as low signalintensity (arrows).


Intraventricular/germinal layerhaemorrhage

GLH is demonstrated as low signal onT2 weighted ima-ging andhigh SI onT1weighted imaging. It canbe di¡eren-tiated from the normal germinal layer by its irregularappearance and its slightly more hypointense SI on T2weighted imaging (Fig.16).

Periventricular haemorrhagic infarction

PHI is a consequence of large IVH obstructing the term-inal veins, and results in interruption of projection andassociation ¢bres as well as oligodendroglial damage,which disrupts myelination. It is demonstrated as a fan-shaped lesion of low SI on T2 weighted FSE imaging(Fig.17). In surviving infants, a porencephalic cyst usuallydevelops at the site of the lesion.The appearance ofmye-lin in the PLIC at term equivalent age has been shown topredict the development of hemiplegia in these infants.23

Periventricular leukomalacia

PVL is a form of whitematter damage that has two com-ponents: focal cyst formation and di¡use white matter

Figure 17 Periventricular haemorrhagic infarction. Preterminfantborn at 27weeksgestation andimagedat 3 d.T2weightedfast spin echo sequence (FSE 3500/208e¡ ms). In the sagittalplane.There is extensive low signal intensity consistent with in-traventricular haemorrhage.There is additionallow signal inten-sity in a fan-shaped distribution in the frontalwhitematter (longarrow).There is adjacent abnormal increased signal intensity ex-tending out to the cortex (short arrow).This is consistent withoedematous or ischaemic tissue. It showed signs of infarction athistology.

Figure 19 Di¡useexcessivehighsignalintensity (DEHSI). Pre-term infant born at 26 weeks gestation and imaged at termequivalent age.T2 weighted fast spin echo sequence (FSE 3500/208e¡ ms).There is excessive high signal intensity throughouttheperiventricular whitematter.


injury.Traditionally,PVLwas thought to be due to ischae-mia but recent studies also implicate infection.24,25

Acutely, PVL is demonstrated as hypointense periventri-cular regions onT1weighted imaging which are hyperin-tense on T2 weighted imaging. Additionally, areas ofshort T1, presumably a haemorrhagic component, havebeen identi¢ed in the acute/subacute stage.26 On DWI,PVL is demonstrated as high SI in the acute stage.Theseareasmaybecome cystic (Fig.18) and lead to dilatation ofthe lateral ventricles, particularly in the region of the oc-cipital horn (Fig.18).PVL is associatedwith delayedorde-¢cient myelination.The late imaging ¢ndings in PVL mayresemble those found in termborn infantswith perinatalacquired haemorrhagic lesions.21

Three-dimensional MRI has demonstrated that pre-term infants with PVL have a reduced cortical grey mat-ter volume at term comparedwith both preterm infantswith no evidence of PVL and normal term control in-fants.3 These ¢ndings suggest that PVL has an impact oncerebral cortical development, which may explain thecognitive de¢cits associatedwith this condition.

Di¡use excessive high signal intensity(DEHSI)

Previous studies have also shown that the preterm infantat term appears to have areas of excessive longT2 (DEH-SI) within the cerebral whitematter.8 These changes aremostmarkedin theperiventricular whitematter andde-crease with age (Fig. 19). DEHSI can be quanti¢ed and is

Figure 18 Periventricular leucomalacia. Infant born at 32 weeksfewdayslater. (a) Inversionrecovery sequence (IR 3800/30/950ms).(b) Inversionrecoverysequence (IR 3600/30/700ms) at15monthsoiorly (arrow) and a paucityofmyelination.

associated with an increase inT1 and T2 values. It is un-clear what this represents in pathological terms but itmay represent a form of di¡use white matter disease inthe preterm infant.

gestation with evidence of cyst formation on cranial ultrasound aThere is extensive cyst formation aroundbothventricles (arrows).f age.Thereisirregular ventriculardilatation,mostmarkedposter-


ACKNOWLEDGEMENTSWe are grateful for the support of the Medical ResearchCouncil, Philips Medical Systems, the Gar¢eld WestonFoundation andWellbeing.

REFERENCES

1. Ajayi-Obe M, Saeed N, Cowan F M, Rutherford M A, Edwards A

D. Reduced development of cerebral cortex in extremely preterm

infants. Lancet 2000; 356: 1162–1163.

2. Inder T E, Huppi P S, Warfield S et al. Periventricular white matter

injury in the premature infant is followed by reduced cerebral

cortical gray matter volume at term. Ann Neurol 1999; 46: 755–

760.

3. Huppi P S, Murphy B, Maier S E et al. Microstructural brain

development after perinatal cerebral white matter injury assessed

by diffusion tensor magnetic resonance imaging. Pediatrics 2001;

107: 455–460.

4. Rutherford M A, Pennock J M, Dubowitz L M S, Cowan F M,

Bydder G M. Does the brain regenerate after perinatal infarction?

Eur J Paediatr Neurol 1997; 1: 13–18.

5. Barkovich A J. Concepts of myelin and myelination in neuro-

radiology. Am J Neuroradiol 2000; 21: 1099–1109.

6. Barkovich A J, Kjos B O, Jackson D E Jr, Norman D. Normal

maturation of the neonatal and infant brain: MR imaging at 1.5 T.

Radiology 1988; 166: 173–180.

7. Battin M R, Maalouf E F, Counsell S J et al. Magnetic resonance

imaging of the brain in very preterm infants: visualization of the

germinal matrix, early myelination, and cortical folding. Pediatrics

1998; 101: 957–962.

8. Maalouf E F, Duggan P J, Rutherford M A et al. Magnetic resonance

imaging of the brain in a cohort of extremely preterm infants. J

Pediatr 1999; 135: 351–357.

9. Felderhoff-Mueser U, Rutherford M A, Squier W V et al.

Relationship between MR imaging and histopathologic findings of

the brain in extremely sick preterm infants. Am J Neuroradiol

1999; 20: 1349–1357.

10. Counsell S J, Maalouf E F, Fletcher A M et al. Magnetic resonance

imaging assessment of myelination in the very preterm brain. Am J

Neuroradiol 23: 872–881.

11. Counsell S J, Kennea N L, Herlihy A L et al. T2 relaxation values in

the developing preterm brain. ISMRM 2001.

12. Barkovich A J. MR and CT evaluation of profound neonatal and

infantile asphyxia. Am J Neuroradiol 1992; 13: 959–972.

13. Maalouf E, Battin M, Counsell S, Rutherford M, Mansur A.

Arthrogryposis multiplex congenita and bilateral midbrain infarc-

tion following maternal overdose of coproxamol. Eur J Paediatr

Neurol 1997; 5/6: 1–4.

14. Chugani H T, Phelps M E. Maturational changes in cerebral

function in infants determined by 18 FDG positron emission

tomography. Science 1986; 231: 840–843.

15. Rutherford M A, Pennock J, Counsell S et al. Abnormal magnetic

resonance signal in the internal capsule predicts poor develop-

mental outcome in infants with hypoxic–ischaemic encephalo-

pathy. Pediatrics 1998; 102: 323–328.

16. Mercuri E, Cowan F, Rutherford M, Acolet D, Pennock J,

Dubowitz L. Ischaemic and haemorrhagic brain lesions in

newborns with seizures and normal Apgar scores. Arch Dis Child

Fetal Neonatal Edn 1995; 73: F67–F74.

17. Barkovich A J, Ali F A, Rowley H A, Bass N. Imaging

patterns of neonatal hypoglycemia. Am J Neuroradiol 1998; 19:

523–528.

18. Traill Z, Squier M, Anslow P. Brain imaging in neonatal

hypoglycaemia. Arch Dis Child Fetal Neonatal Edn 1998; 79:

F145–F147.

19. de Vries L S, Groenendaal F, Eken P, van Haastert I C, Rademaker

K J, Meiners L C. Infarcts in the vascular distribution of the middle

cerebral artery in preterm and fullterm infants. Neuropediatrics

1997; 28: 88–96.

20. Mercuri E, Cowan F, Girish Gupte G et al. Prothrombotic

disorders and abnormal neurodevelopmental outcome in infants

with neonatal cerebral infarction. J Pediatr 2001; 107: 1400–1404.

21. Rutherford M A. Haemorrhagic lesions of the newborn brain. In:

Rutherford MA (ed.). MRI of the Neonatal Brain. London: WB

Saunders, 2001; 171–200.

22. Stewart A L, Rifkin L, Amess P N et al. Brain structure and

neurocognitive and behavioural function in adolescents who were

born very preterm. Lancet 1999; 353: 1653–1657.

23. De Vries L S, Groenendaal F, van Haastert I C, Eken P, Rademaker

K J, Meiners L C. Asymmetrical myelination of the posterior limb

of the internal capsule in infants with periventricular haemorrhagic

infarction: an early predictor of hemiplegia. Neuropediatrics 1999;

30: 314–319.

24. Dammann O, Leviton A. Maternal intrauterine infection, cyto-

kines, and brain damage in the preterm newborn. Pediatr Res

1997; 42: 1–8.

25. Duggan P J, Maalouf E F, Watts T L et al. Intrauterine T-cell

activation and increased proinflammatory cytokine concentrations

in preterm infants with cerebral lesions. Lancet 2001; 358: 1699–

1700.

26. Sie L T, van der Knaap M S, Oosting J, de Vries L S, Lafeber H N,

Valk J. MR patterns of hypoxic–ischemic brain damage after

prenatal, perinatal or postnatal asphyxia. Neuropediatrics 2000;

31: 128–136.

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