magnetic resonance imaging of the neonatal brain · 2017-08-27 · neonatal magnetic resonance (mr)...

Indian Journal of Pediatrics, Volume 74—February, 2007 173

Correspondence and Reprint requests : Dr. Sudipta Roychowdhury,Clinical Assistant Professor of Radiology, UMDNJ – Robert WoodJohnson Medical School, University Radiology Group, 579ACranbury Road, East Brunswick, NJ 08816. Fax : 732-937-8892.

Magnetic Resonance Imaging of the Neonatal Brain

Ariel Prager1,2 and Sudipta Roychowdhury1,2,3,4

1University of Medicine and Dentistry of New Jersey – Robert Wood Johnson Medical School, New Brunswick, NJ2Robert Wood Johnson University Hospital, New Brunswick, NJ3Saint Peters University Hospital, New Brunswick, NJ4University Radiology Group

ABSTRACT

Neonatal magnetic resonance (MR) imaging is rapidly becoming the preferred modality for the evaluation of central nervoussystem disorders in the newborn. Recent literature supports the value of this imaging technique in diagnosing ischemic,hemorrhagic and infectious disease processes in the premature and full-term neonatal brain. Recent data in prematurenewborns with neurological injury also suggest a role for MR imaging in determining long-term neurodevelopmental outcomes.This review article provides a framework and overview on neonatal MR imaging techniques and examines the literature orradiological disease patterns and prognostic implications in common neurological disorders. [Indian J Pediatr 2007; 74 (2) : 173-184] E-mail: [email protected]

Key words : Neonate; Magnetic resonance imaging; Central nervous system; Neurodevelopmental outcomes

SYMPOSIUM : NEONATOLOGY – IIIEvidence and Experience in Neonatal Medicine

Neonatal magnetic resonance (MR) imaging is a relativelynew technique which has rapidly become the study ofchoice for the evaluation central nervous systemsdisorders in newborns. MR imaging provides excellentanatomical depiction of the brain which far surpassescranial ultrasound and computed tomography. Themultiple specialized MR sequences allow for greatersensitivity and specificity for the detection ofparenchymal and extra-axial processes. In addition, MRimaging is the only technique which can distinguish thepresence or absence of myelin in the neonatal brain. Thistechnique has become more widely available with theuniversal increase in hospital-based MR scanners in closeproximity to the neonatal intensive care unit. Thedevelopment of MR compatible incubators and neonatalcoils has improved patient safety and image quality.Neonatal MR imaging is rapidly becoming important inpredicting neurodevelopmental outcomes, and the futureof MR imaging is directed at understanding theprognostic implications of CNS disease within newborns. This article provides a basic framework and overview onneonatal MR imaging techniques, applications, diseasepatterns and prognostic implications in commonneurological disorders.

MR IMAGING TECHNIQUE FOR THENEONATAL BRAIN

MR Safety

While MR imaging does not use ionization radiation toacquire images such as in computed tomography or plainradiographs, radiofrequency (RF) pulses are used todeflect the proton spins within the tissues for the variousMR imaging sequences. The RF pulses deposit energy inthe form of heat into the tissues. The rate in which RFenergy is deposited is defined as the specific absorptionrate, which is measured in watts per kilogram (W/Kg).The FDA guidelines for the specific absorption rate for thebrain require that the operating values are less than 3 W/Kg for any 10-minute period.1, 2 These parameters areespecially important in newborns compared to olderpediatric patients and adults, because of the limitedthermoregulation capability of neonates. All MRmagnets, RF pulses and MR coil combinations shouldhave specific absorption rates which stay within the strictguidelines to prevent excess deposition of RF energy andinadvertent rise in patient temperature.

The high magnetic field of the MR scanner room hasdemanded the development of MR-compatiblemonitoring, ventilation and transportation devices forpatient safety. With the advent of such MR-compatibledevices, even relatively unstable patients can betransported and monitored in the MR scanner.

A. Prager and S. Roychowdhury

174 Indian Journal of Pediatrics, Volume 74—February, 2007

MR Coils

Over the last few years, the quality and safety of neonatalMR imaging has steadily increased with the developmentof dedicated neonatal MR scanners, neonatal imagingcoils and MR compatible incubators. In certaininstitutions, dedicated neonatal MR scanners have beeninstalled in close proximity to the neonatal intensive careunit.3, 4 However, these dedicated MR scanners arecurrently expensive for most institutions to acquire. Inaddition, these MR scanners usually have low fieldmagnets, which have a lower to signal-to-noise ratio(SNR) than a high field 1.5 Tesla scanner. Another optionis to use a dedicated neonatal head coil in a conventional1.5 Tesla MR scanner to optimize imaging.

At the authors' institution they use an MR compatibleincubator with an attachable dedicated neonatal head coil(Neonate Imaging Sub System, Advanced ImagingResearch, Cleveland OH). The signal-to-noise ratio ofimages obtained with an MR compatible incubator with adedicated head coil is 2.3 times that of a standard MR coilin age-matched patients.5 The incubator is easy totransport from the neonatal intensive care unit to the MRscanner. The device, in addition to being an incubatorwith temperature and humidity controls, has a ventilator,infusion pumps, physiologic monitors, tanks, and MR-compatible intravenous lines and poles. By moving thepatient into the incubator in the NICU, the time that thenewborn spends outside the NICU or outside theincubator can be minimized. This type of deviceenhances both patient safety and the quality of MRimaging.

MR Techniques

The conventional MR brain protocol includes T1-weighted sequences, T2-weighted sequences and gradientecho (GRE) sequences. T1-weighted and inversionrecovery sequences provide excellent anatomicinformation as well as high contrast between gray andwhite matter. Three-dimensional inversion recoverytechniques provide thin sections through the entire brainwith a short acquisition time and T1-weighted contrast.T2-weighted sequences provide good contrast resolutionbetween gray matter, unmyelinated white matter andmyelinated white matter. The authors typically use fastspin-echo (FSE) T2-weighted sequences to limit theacquisition time while maintaining adequate contrastresolution between the gray and white matter. Thedisadvantage of the FSE T2-weighted sequence is thereduction of magnetic susceptibility for the detection ofintracranial hemorrhage. For this reason, gradient echosequences are part of the protocol. Gradient echo (GRE)sequences provide increased sensitivity for the detectionof T2*-weighted magnetic susceptibility. This isespecially important for diagnosing intracranialhemorrhage, which locally distorts the magnetic fieldbecause of the presence of the Fe molecule within blood

products. Subtle germinal matrix or intraventricularhemorrhage may sometimes only be detectable with theGRE sequence.

Diffusion-weighted imaging (DWI) measures therandom motion of water molecules. The directionality oranisotropy of diffusion within the brain is affected by thepresence or absence of myelin within white matter tracts.6,

7 Myelinated white matter tracts allow greater waterdiffusion parallel to the tract and restrict diffusionperpendicular to the tract. This anisotropy of diffusionnecessitates the acquisition of diffusion-weighted imagesin three perpendicular directions to form the compositeDWI image, called the trace or isotropic diffusion image.Diffusion can also be quantified by measuring anapparent diffusion coefficient (ADC). Acute infarctsdemonstrate a marked reduction of water diffusionthrough an incompletely understood mechanism, whichis postulated to be related to cytotoxic edema.8,9 Therefore,acute infarcts typically have increased signal on DWI andhave decreased apparent diffusion coefficients.Diffusion-weighted imaging also has a role in thedetection of acute hypoxic-ischemic injury in neonates.

Proton MR spectroscopy provides a chemical analysisof the tissue within the brain. Different protons withinthe brain experience slightly different magnetic fieldsdepending on their local molecular environments. Thereare specific metabolites which have been identified onMR spectroscopy of the brain. Using the pattern of themetabolites which include n-acetyl aspartate, choline,creatine, lactate, amino acids and other molecules, certaindiseases and disorders can be diagnosed and followed.Unmyelinated white matter characteristically haselevated choline which distinguishes it from myelinatedwhite matter. Choline peaks are, therefore, normallyelevated in most of neonatal white matter. N-acetylaspartate is a normal neuronal marker and isnonspecifically decreased in a variety of disorders.Lactate is elevated in situations in which anaerobicmetabolism predominates such as ischemia, hypoxic-ischemic injury, and other metabolic disorders.

Sedation

Sedation is usually unnecessary for neonatal MR imaging.A newborn usually sleeps for most of the day and usuallyfalls sound asleep after regular breast-feeding or bottle-feeding. Therefore, pharmacologic sedation is usually notused for MR imaging if the study is performed after aregular feeding and after a period of sleep-deprivation ofthe newborn. In a small subset of neonates, chloralhydrate (50 mg/Kg) is used for sedation and monitoredby a pediatric anesthesiologist or neonatal intensive carestaff.

NORMAL MR APPEARANCE OF THENEONATAL BRAIN

The most characteristic finding in the normal neonatal



brain is the almost complete lack of myelination. MRimaging is exquisitely sensitive to the myelination ofwhite matter. Unmyelinated white matter is hyperintenseon T2-weighted images and hypointense on T1-weightedimages. There is a predictable course of myelinationbased on the gestational age of the newborn.10 Althoughmost neonatal white matter is unmyelinated, termneonates typically demonstrate myelination of the coronaradiate, primary motor and sensory cortex,ventroposterolateral nuclei of the thalami, mediallemnisci, medial longitudinal fasciculus, and gracile andcuneate nuclei.11 Superior and inferior cerebellarpeduncles but not middle cerebellar peduncles aremyelinated at term. Portions of the vermis but not thecerebellar peduncles are myelinated. The absence ofmyelin at the appropriate age can signal delayedmyelination or dysmyelinating disorders.

INJURIES OF PREMATURITY

White Matter Injury of Prematurity

Neonatal white matter injury is a common complicationof prematurity and is often an end-result of perinatalhypoxic-ischemic events in this population.12 Whilehypoxic-ischemic encephalopathy (HIE) is the mostcommon cause, other etiologies include infections,metabolic disease, and hydrocephalus.13 The pattern ofwhite matter injury is traditionally described as small,non-hemorrhagic, gliotic lesions appearing symmetricallyin periventricular areas - particularly in the trigone andadjacent to the foramen of Monro. This distribution ofinjury has earned the classic title of periventricularleukomalacia (PVL). However, several authors13, 14 cautionthat white matter involvement is not always confined toperiventricular zones and may in fact extend deep intoadjacent subcortical white matter or the centrumsemiovale. The gliotic lesions may become cystic andcavitated. Alternatively, the lesions may remain non-cystic. Sie and colleagues15 suggest that clinical outcomecorrelates more with the extent of injury than with lesionmorphology. Neonatal MR imaging allows therecognition of patterns of injury which may predict theprognoses of the newborns. There is no consensus yet asto the exact etiology of these lesions, but the propensityfor white matter damage in preterm infants is likelyrelated to the intrinsic vulnerability of the prematuretissue in the face of oxygen deprivation. Several factorsconferring this vulnerability are proposed includingoligodendrocytic susceptibility to damage from freeradicals,16 the absence of compensatory hyperemia duringhypotension,17 and an increase in anaerobic glycolysisduring hypoxia.18 Neonatologists should be aware of thevarious imaging techniques that allow for earlyrecognition and evaluation of this potentially devastatingdisease process.

As one of the first methods studied in PVL, cranial

ultrasonography remains unpromising in the acutesetting with its relatively poor sensitivity for non-cavitarywhite matter lesions.19-21 One study22 demonstrated thatup to 70% of hypoxic-ischemic white matter lesions aremissed in the acute phase on ultrasound. Acute lesionsdemonstrate slight to intense echogenicity in the trigone.The sonographic features of PVL are more prominent inthe subacute phase (2-6 weeks) when necrotic tissuebegins to dissolve, leaving behind distinct hypoechoiccavitations.23 Nevertheless, ultrasound, a relatively simpletechnique, remains the initial survey of choice inpremature infants experiencing cerebral oxygendeprivation because of its portability and readyavailability for follow-up imaging.

Conventional MR imaging exhibits superior sensitivityfor non-cavitary PVL, especially in the acute setting (2-5days). Lesions appear as small punctate hyperintenseareas on T1-weighted images,20, 21 which are likely to be aproduct of reactive gliosis.24 Cavitations are also visible asareas of hypointensity on T1-weighted images andhyperintensity on T2-weighted images. MR imaging iscapable of detecting structural changes of chronic PVLincluding white matter atrophy, callosal thinning and exvacuo ventricular dilation.11 However, Childs et al25

cautions that MR evaluation of frontal periventricularwhite matter becomes difficult in neonates of less than 34weeks gestational age, due to migrating glia that interferewith white matter signal.

Diffusion-weighted imaging (DWI) is yet anotherpromising technique for early detection of PVL.Thompson et al26 suggests that DWI can reveal changesthat are not observed on any other imaging modality.Findings include hyperintensity on DWI and diminishedapparent diffusion coefficients in the periventricularwhite matter in the first few days after injury. DWIfindings are most advantageous in the acute setting asthese are observed before any abnormality appears onultrasound or conventional MR images.27 Decreasedapparent diffusion coefficients are usually limited to theacute phase as parenchymal changes normalize within thefirst five days of injury.

Germinal Matrix and Intraventricular Hemorrhage

Intraventricular hemorrhage (IVH) comprises a spectrumof pathological processes that result from blood filling inand around the ventricles. The incidence of IVH is directlyrelated to prematurity and rarely occurs in full termneonates. Though multifactorial in etiology, the tendencyfor hemorrhage is most likely associated withexceptionally fragile capillaries in residual germinalmatrix that are subjected to oscillating blood pressure.11

Blood from ruptured capillaries may remain confined tothe ependymal surface or extravasate into the ventricles,leading to subsequent complications. Of particularconcern is the potential for clot obstruction within the CSFpathways, resulting in hydrocephalus. Severehydrocephalus is predictive of a poor developmental



prognosis.19 Papile28 and Volpe29 established a gradingsystem for the sonographic evaluation of IVH severity.Grade I hemorrhage is defined as an isolated germinalmatrix hemorrhage (GMH) without extension into theventricular cavity. A grade II classification is assigned toGMH with accompanying intraventricular blood fillingless than half of the ventricular space. Grade IIIhemorrhage refers to GMH with blood filling greater thanhalf of the ventricular area. A grade IV classification isreserved for cases of GMH with secondary periventricularhemorrhagic venous infarction (PVHI). This gradingsystem is now widely accepted as a reliable prognostictool in the evaluation of IVH.

GMH is the most common form of neonatalintracranial hemorrhage and is typically seen in preterminfants.29 As a subtype of IVH, GMH is classified as aninjury of prematurity with an incidence inverselyproportional to gestational age and birth weight. Severalstudies30-32 have shown that GMH shows a markeddecline in incidence after 34 weeks of gestation. Thisobservation can be explained by the tendency for matrixinvolution beginning in the final weeks of the secondtrimester. Germinal matrix tissue in the caudothalamicnotch is the last to involute and is, therefore, statisticallythe region of greatest concern for hemorrhage. The onsetof hemorrhage is variable but up to 40% of cases occurwithin the first five hours after birth.33 GMH falls on acontinuum of intraventricular hemorrhage (IVH) and isconsidered to be the injury of best prognostic outcomewhen found alone.28, 29 Isolated subependymalhemorrhage can in fact be clinically silent. Subsequentcomplications of GMH may be severe and include high-grade IVH with hydrocephalus and PVHI. The possibilityof GMH in preterm infants that exhibit acute neurologicaldecline within the first four days of life19 should beconsidered.

Cranial ultrasonography and conventional MRimaging have been two widely studied imagingmodalities for early detection of GMH. According toTriulzi and colleagues,11 cranial ultrasonography isinitially the technique of choice for evaluating GMH as itis sensitive and easiest to perform. In addition, ultrasoundcan be repeated multiple times to monitor for ventricularenlargement in anticipation of complicated IVH.Findings on ultrasound include areas of increasedechogenicity in the ventricular wall.13 While ultrasoundcan be useful in detecting blood within the subependymalspace, some researchers13 argue that conventional MRimaging is as sensitive and probably more specific,especially in the acute setting. MR imaging exhibits asuperior capacity to differentiate blood from other lesionsafter the hyperacute phase11 (Fig. 1). Acute hemorrhagicfoci on T1-weighted images appear as small areas ofnormal to increased signal and can be confirmed on T2-weighted sequences as ovoid areas of distincthypointensity. MR also offers the advantage of

identifying subependymal bleeds in the subacute andchronic phases with substantial sensitivity forhemorrhage.11 Gradient echo (GRE) sequences areexquisitely sensitive to hemosiderin deposits which maybe missed on other MR sequences and onneurosonography. Moreover, MR imaging is superior toultrasound in detecting and evaluating a wider array ofGMH complications including IVH, hydrocephalus, andPVHI. In the experience of Zuerrer and colleagues,34

conventional and gradient echo MR sequences canidentify acute (3-7 days) and chronic (several months)phases of IVH. Barkovich13 recommends rescanning thepatient one week after initial documentation of IVH toexclude subsequent ventricular enlargement. Insummary, conventional MR is currently the preferredimaging modality for the diagnosis and evaluation ofacute or subacute GMH and its IVH sequelae. Cranialultrasonography remains useful for the hyperacutesetting, for repeated follow-up imaging or when MRfacilities are unavailable.

Periventricular Hemorrhagic Infarction

Intraventricular hemorrhage can cause mass effect,resulting in obstruction of venous outflow fromperiventricular parenchymal tissue and culminating inhemorrhagic infarction35 secondary to venoushypertension. Approximately 15% of neonates with aninitial diagnosis of IVH progress to this form of venousinfarction, which is also known as periventricularhemorrhagic infarction (PVHI).36 Most cases of PVHIoccur within the first 96 hours after birth.37 These lesionseventually undergo liquefaction leaving behind cysts thatmay communicate with the ventricles. In contrast to thesymmetric multicystic pattern seen in PVL, the lesions ofPVHI tend to be asymmetric or unilocular in character.Clinical presentations of PVHI are variable but mayinclude apnea, bradycardia, cyanosis, severe motorimpairment, seizures or loss of consciousness. Earlydiagnosis and management of PVHI is crucial inpreventing further neurodevlopmental deficits.

While PVHI is detectable on cranial sonography, MRimaging is more sensitive than ultrasound in the detectionand quantification of PVHI. The deep location of theseperiventricular lesions allows detection on cranialultrasonography.13 Occlusion of draining veins cansometimes be demonstrated with color doppler.38, 39

Ultrasound lacks the ability to quantify the amount ofhemorrhage present.13 Conventional MR offers theadvantage of differentiating hemorrhagic and necroticcomponents of PVHI (Fig. 1). T2-weighted sequencesdisplay hemorrhage as regions of low signal, contrastedagainst the neighboring venous infarct which appearshyperintense.37 The superior tissue differentiation of MRimaging allows for more precise estimates of infarct sizeand location.11



HYPOXIC-ISCHEMIC INJURY

Inadequate brain oxygenation is the major recognizedcause of perinatal morbidity and mortality29 and mayresult from either hypoxic, ischemic or combinedprocesses.40 Some of the more common prenatal andperinatal processes include birth injury, hematologicabnormalities and hypovolemia. Significant parenchymalinjury may occur with prolonged oxygen deprivation – acondition known as hypoxic-ischemic encephalopathy(HIE). Without appropriate intervention, the neonatemay sustain severe motor and cognitive impairment.41, 42

Clinical risk factors for developing HIE are linked toperinatal state and include fetal heart rate abnormalitiesdirectly preceding birth, low apgar scores, acidosis andmajor resuscitation during delivery.41, 42 Clinicalmanifestations of HIE vary and may appear as early as 24-48 hours after the onset of hypoxic or ischemic events. Adistinction should be made between HIE and braininfarction as their clinical presentations are similar.However, infarction is a focal vascular insult with arelatively good prognosis while HIE is a diffuse processwith a less favorable outcome.

Both term and preterm neonates are susceptible tohypoxic-ischemic brain injury but their disease patternsdiffer. Chugani et al43 suggests that changes resulting fromhypoxic-ischemic injury are strictly related to the state ofbrain development and maturation. While HIE in adultsmanifests as diffuse gray matter injury, neonatal diseasepatterns involve select regions of both gray and whitematter. Regional selectivity for neonatal HIE is dependenton the varying metabolic demands across different braintissue, which in turn varies with the level of brain

Fig 1a

Fig 1. This preterm infant developed germinal matrix hemorrhage(GMH), intraventricular hemorrhage (IVH) andperiventricular hemorrhagic infarction (PVHI). Axial T2-weighted image (Fig. 1a) demonstrates hypointense rightfrontral PVHI (arrow) with surrounding white matter injurywhich is hyperintense. Gradient echo (GRE) image (Fig. 1b),which is the most sensitive MR sequence for detectinghemorrhage, shows the subtle germinal matrix hemorrhage(arrow) in addition to the PVHI. Sagittal T2-weighted imagedemonstrates the IVH in the occipital horn (arrow) of thelateral ventricle as well as PVHI.

Fig 1b

Fig 1c



the basal ganglia45-49 as well as the lateral thalamus,hippocampus, and corticospinal tracts.48, 50, 51 The vascularboundary zones are usually spared. Basal ganglia injuryis more common than the parasagittal pattern11 and baresthe worst prognosis.45, 52 Severe gray matter injury mayeventually give rise to multicystic encephalopathy. Theavailability of new time-bound therapies for HIE such asneuroprotective agents reaffirms the importance of earlyradiologic diagnosis.53

Imaging features of HIE will vary depending ongestational age and severity of oxygen deprivation. Termneonates with mild to moderate hypoperfusion willdevelop parasagittal injury.54 Cranial ultrasonographyand computed tomography (CT) cannot detectparasagittal or watershed injury in the acute phase.53

Conventional MR imaging with the addition of DWI hasincreased sensitivity for acute parasagittal lesions whichare hypointense on T1-weighted images, hyperintense onT2-weighted images49, 55, 56 and hyperintense on DWI. MRscans of term infants with chronic HIE may reveal corticalatrophy and thinning49 on T1-weighted and T2-weightedsequences.

Several authors57-60 argue that proton spectroscopy isthe most sensitive modality for detecting parasagittal HIEwithin the first 24 hours of injury. Findings includeincreased brain lactate and a diminished N-acetylasparatelevel. These results are promising and may advocate

Fig. 2. This term infant developed hypoxic-ischemic injury whichpredominantly affected the watershed cortex andsubcortical white matter of bilateral hemispheres. Axial T2-weighted (figure 2a, arrows), axial FLAIR (Fig. 2b, arrows)and coronal T1-weighted images (Fig. 2c, arrows)demonstrate the watershed hypoxic-ischemic injury pattern.

Fig 2a

Fig 2b

Fig 2c

maturity. As discussed earlier, HIE in preterm infantsexhibits predominantly white matter injury (ie. PVL).12 Incontrast, the pattern observed in term infants involvesnecrosis of select gray and white matter structures.44 Mildto moderate hypotension in term neonates tends to yieldparasagittal injury consisting of cortical necrosis andnecrosis of underlying white matter in a vascularwatershed distribution (Fig. 2). Parenchymal injuryresulting from severe hypotension has a predilection for



proton spectroscopy as a screening tool for parasagittalHIE.

DWI data are limited in the pediatric population40 butevidence exists for imaging changes occurring throughoutthe course of HIE. Several authors57, 61-65 caution that DWIcan give false negative results if performed within the firstseveral hours of hypoxic-ischemic injury. A missed HIEdiagnosis could yield devastating outcomes for thepatient involved. After the first 24 hours, the lesionsappear hyperintense.53 As the HIE lesions evolve from theacute to the chronic phases, the initial decreased diffusionin the acute phase progresses to increased diffusion in thechronic phase.66-68 This observed DWI phenomenon islikely attributed to fluid shifts between intracellular andextracellular compartments that occur over the course ofcell injury.8, 9, 69 More data from the neonatal population isneeded to determine the reliability of diffusion weightedsequences in the detection and diagnosis of hypoxic-ischemic injury.

As with watershed injury, ultrasound and CT are non-diagnostic for basal ganglia insult in the acute setting.13 Inthe experience of Barkovich,13 conventional MR is thetechnique of choice for this pattern (Fig. 3). In the acutephase (1-2 days), hypointense foci in the basal gangliaappear on T1-weighted sequences, which correspond tohyperintense lesions found on T2 images. The areas ofhypointensity on T1 become hyperintense approximatelytwo to three days after injury. Finally, lesions on T2eventually assume a hypointense appearance at six to tendays after injury.70 These changes are typical whetheroccurring in the thalamus, perirolandic cortex,hippocampal formation, or the dorsal mesencephalic

structures. Diffuse damage resulting in multicysticencephalopathy may occur if anoxia is severe orprolonged.11 The medulla and cerebellum however, arespared in this progression. Proton MR spectroscopy andDWI demonstrate basal ganglia injury earlier than any ofthe other imaging modalities.60 Robertson et al64 hasconfirmed this advantage of diffusion imaging but warnsthat initial findings may markedly underestimate the finalextent of injury. Moreover, other authors57, 63, 64 cautionthat as with parasagittal injury, DWI may yield falsenegative results within the first few hours. Any changesobserved with DWI normalize within the first five to sixdays.60, 65

CEREBRAL INFARCTION

Cerebral infarction of the neonate is most often idiopathic,but coagulopathy is the most common known etiology inthis population. Infarction typically ensues within the firstfew days of life and is likely associated with complexhemodynamic changes occurring during this timeperiod.11 Clinical presentations of infarction tend tooverlap with those of HIE, but seizures are the mostcommon sign.29

Multiple modalities have been studied for their efficacyin detecting infarction. As in HIE, cranialultrasonography11 and CT40 are poorly sensitive for acuteischemia. Conventional MR imaging however has beennamed by Triulzi and colleagues11 as the overall tool ofchoice for evaluating focal infarction (Fig. 4). On T1-weighted and T2-weighted images, infarcts become

Fig. 3. This newborn presented with severe hypoxic-ischemic encephalopathy resulting in a basal ganglia pattern of injury. Axial FLAIRimage (Fig. 3a, arrows) and axial diffusion weighted image (Fig. 3b, arrows) show hyperintense lesions within bilateral basal ganglia

Fig 3a Fig 3b



readily visible after two or three days70 as areasdemonstrating loss of gray-white matter differentiation.Connelly et al71 reports that changes observed on DWIappear before any abnormalities can be viewed onconventional MR. DWI demonstrates hyperintensity withdecreased apparent diffusion coefficients (ADC) as earlyas 20 minutes after an acute infarction. Preliminary datasuggests that DWI is the most effective tool for thedetection of acute infarcts.64 DWI can also better identifyinfarct boundaries and can pinpoint irreversible lesions.72

MR arteriography and MR venography can be used inconjunction with MR imaging of the brain to diagnosecauses of arterial and venous infarction. MRarteriography may show occlusion of intracranial vesselsas a cause of the infarct. MR venography maydemonstrate venous sinus thrombosis as the cause ofvenous infarction.

INFECTIONS

Bacterial Meningitis

Infants are highly susceptible to bacterial meningitis,which is the most common neonatal CNS bacterialinfection.29 Meningitis can have an early onset with severesystemic symptoms appearing in the first few days of life

and a high mortality rate. The pathogen in such cases islikely to have originated in the birth canal. Alternatively,meningitis may first appear after the first week of life asa result of pathogenic exposure in the infant’senvironment. Mortality is not as likely in the late-onsetform and patients typically present with meningitis in theabsence of systemic symptoms. The most commoncausative bacterial pathogens are group B streptococcus,Escherichia coli, Listeria monocytogenes, Staphylococcusaureas, and Pseudomonas aeruginosa. The pathophysiologyof bacterial meningitis is complex. The process beginswith irritation of the meninges and the ventricles. Markedcerebral edema occurs early in the infection. Inflammationspreads along cerebral vessels inducing a vasculitis,which in turn gives rise to hemorrhagic infarction.Perivascular inflammation extends to neighboringparynchemal tissue and cerebritis results. Ischemia orcerebral hypoperfusion may occur from severevasospasm in inflamed vessels. Bacterial meningitis canbe complicated by hydrocephalus, cerebral infarction,subdural empyema, or abscess.

The diagnosis of uncomplicated bacterial meningitis isestablished with clinical evaluation, laboratory data, andlumbar puncture. Neuroimaging is used to evaluate thesecondary complications of the disease. Conventional MRis the study of choice for detecting the wide array of

Fig. 4. This term newborn presented with a seizure and was found to have an acute left frontal lobe infarct. T2-weighted image (Fig. 4a,arrow) demonstrates subtle loss of gray-white matter differentiation within the left frontal lobe. Axial diffusion weighted image (Fig.4b) shows striking hyperintensity (arrow) within the left frontal lobe confirming decreased diffusion in an acute infarction.

Fig 4a Fig 4b



sequelae that can result. MR is particularly adept atdemonstrating small lacunar infarcts in the brainstem,basal ganglia, and white matter. Meningitis can bedetected on post-gadolinium T1-weighted images asabnormal leptomeningeal or cranial nerve enhancement.Encephalitis is diagnosed as parenchymal areas ofincreased signal on T2-weighted images with occasionalenhancement on post-contrast T1-weighted images.Infarction related to vasculitis is readily diagnosed usingDWI. Post-contrast T1-weighted images are the mostsensitive for demonstrating extra-axial empyemas orsterile effusions. Although empyemas and sterileeffusions may have overlapping MR characteristics,empyemas usually have an avid enhancing rim.

PROGNOSTIC VALUE OF NEONATAL MR IMAGING

Current techniques in neonatal neuroimaging allow forearly detection of various neuropathological processesincluding ischemic, hemorrhagic, metabolic andinfectious states. However, the long-term prognosticimplications of early radiological disease detection are stillunder investigation. Woodward and colleagues73 studiedthis association in 167 preterm infants (gestational age atbirth, 30 weeks or less) as part of a prospectivelongitudinal design. They performed early cranialultrasonography within 48 hours of birth, brain MRI atterm equivalent age, cognitive assessment, pscyhomotortesting, cerebral palsy evaluation, and neurosensorytesting, followed by repeat neurodevelopmental

evaluation at two years of age. MRI findings werequalitatively assessed according to degree of white matterand gray matter involvement. Moderate to severe whitematter abnormalities on MRI at term-equivalent age werefound to be statistically strong predictors of cognitive andpsychomotor delay, cerebral palsy, and neurosensoryimpairment by two years of age. Gray matterabnormalities were also correlated with cognitive delay,motor impairment, and cerebral palsy, but theseassociations were statistically weaker. MRI also proved tobe more sensitive than cranial ultrasonography inidentifying lesions predictive of long-termneurodevelopmental impairment. These findings suggestthat MRI at term-equivalent age can serve as a reliableprognostic guide for physicians and families in themanagement of preterm infants with neurological injury.

A prospective cohort study by Miller et al74 at UCSFinvestigated the prognostic value of specific brain MRIfindings on neurodevelopmental outcome in pretermneonates. They specifically assessed the prognostic valueof white matter involvement, degree of ventriculomegaly,and IVH severity as independent factors. Serial MRI scanswere performed at two distinct time-frames - the firstbefore term-equivalent age (median: 32 weeks GAequivalent) and the second at near term-equivalent age(median: 37 weeks GA equivalent). Outcome measurestaken at a follow-up appointment between 12-18 monthsincluded neuromotor scores and cognitive performance asmeasured by the Mental Developmental Index. Resultsfrom this study showed significant correlations between

Fig. 5. Neonatal MR imaging of the brain can be used for prognostic evaluation of the infant. This preterm newborn developed massiveintraventricular hemorrhage (IVH), severe hydrocephalus and severe periventricular white matter injury which are all independentpredictors of a poor neurodevelopmental outcome. Axial T2-weighted image (5a) demonstrates severe hydrocephalus and extensiveperiventricular white matter injury. Coronal T1-weighted image (Fig. 5b) shows massive IVH (arrow) with severe hydrocephalus

Fig 5a Fig 5b



degree of white matter injury, ventriculomegaly, and IVHfound on early and term-equivalent age MRI withseverity of neurodevelopmental outcome. In addition,initial MRI findings prior to term-equivalent age werestronger predictors of outcome than were findings atterm-equivalent age. The authors confirm the role of MRIas a prognostic tool in preterm neonates and argue that itshould not be necessary to wait until term-equivalent ageto obtain this valuable information.

Dyet and colleagues75 further stratified brain MRIfindings in preterm neonates (23-30 weeks GA) from bothearly post-birth and term-equivalent periods andcorrelated each with prognostic outcome at 18-36 monthsof corrected age. Early post-birth (median: 2 days of life)scans of their neonatal population (n=119) identified awide range of abnormalities including major destructivelesions, hemorrhagic parenchymal infarction, extra-axialhemorrhage, basal ganglia and thalamic abnormalities,cerebellar hemorrhage, punctate white matter lesions,germinal layer hemorrhage, intraventricular hemorrhage,and ventricular dilatation. Findings on later (term-equivalent: 36 weeks postmentstrual age) scans includeddiffuse excessive high signal intensity, hemorrhagicparenchymal infarction, widened extra-axial space, basalganglia and thalamic abnormalities, punctate whitematter lesions, germinal matrix hemorrhage, ventriculardilatation, and periventricular leukomalacia. Clinicaloutcomes were measured at 18-36 months of correctedage with the Griffiths Mental Developmental Scale, whichevaluates locomotor ability, personal-social interaction,hearing, speech, eye-hand coordination, performance,and practical reasoning.

Summative developmental quotients (DQs) werecalculated for each patient. DQs were used in comparingpatient groups with and without a given MRIabnormality. Patients with at least one abnormality on theearly scan happened to have statistically higher DQs thanthose patients with normal initial scans. Moreover, withthe exception of cerebellar hemorrhage and majordestructive lesions, individual findings on early MRIshowed no clear relationship with DQs. In contrast,lesions found at term-equivalent age including diffusewhite matter abnormalities and post-hemorrhagicventricular dilatation were predictive of lower DQs at 18-36 months of corrected age. These results would appearto contradict the findings of Miller et al,74 who showedthat early MRI findings were more predictive of adverseneurodevelopmental outcome. However, Dyet et al75

clarifies that the initial scans of the Miller study wereperformed at a more mature age (median: 32 weeks GAequivalent) than the initial scans of their own study.

MR imaging is beginning to play an important role indevelopmental risk stratification in preterm and termneonates. Imaging abnormalities which appear to be mostpredictive of poor outcome include significant whitematter injury and intraventricular hemorrhage withaccompanying ventricular dilatation (Fig. 5). The

appropriate timing for these screening scans remainscontroversial. Future studies should address theprognostic weight of screening MRI performed at varioustime points in the neonatal period as well as therelationship between early MRI findings and long-termfunctional outcomes beyond two years of age.

CONCLUSION

The advent of MR imaging has contributed significantlyto the early diagnosis of neonatal disease. New scanningmodalities allow for the detection of a wide array ofpathology including injuries of prematurity, infarction,hemorrhage, infection, and other disorders. Informationobtained from neonatal MR imaging can effectively assistpediatric teams in planning appropriate treatment anddetermining long-term neurodevelopmental prognosis.

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