4 Why Image? 2 Roles: Diagnose brain injury in at risk newborns Improve and provide acute medical management/interventionsDetect lesions associated with long-term neurodevelopmental disabilityAppropriate prognosis/predictionsAppropriate tx:Brain coolingPhenobarb? Bumetanide?Redirection?Approp prognosis:CognitiveMotorPsychNeurosensory
5 Prognostic ConcernsClinical evaluation insufficient for prognosticationCerebral Palsy?School Performance?Neurocognitive & neurodevelopmental disabilitiesBehavioral disabilitiesRole for neuroimaging?
6 2 Types of Neonates Preterm Infants Periventricular Leukomalacia Intraventricular HemorrhagePost-hemorrhaghic HydrocephalusPeriventricular Hemorrhagic InfarctionIntraparenchymal HemorrhageCortical and Deep Gray Matter Injury
7 2 Types of Neonates Full term Infant Stroke Intracerebral Hemorrhage Periventricular LeukomalaciaIntraventricular HemorrhageCongenital AnomaliesCortical and Deep Gray Matter Injury
8 Outline Preterm infant: ELGAN / VLBW Term Epidemiology Neuroimaging modalitiesIndications for useFindings and clinical correlatesConclusionsTermNot late preterm infant. Focus on ELGA / VLBWLate preterm – not lots info on imaging on these infants – I suspect most their difficulties are cognitive and we’re still trying to figure out their deficits and then ultimatley how to identify them early.
9 The brain is a wonderful organ; it starts working the moment you get up in the morning and does not stop until you get into the office Robert Frost
11 Epidemiology: Preterm Infant ELGAN/ VLBW:number preterm infants and survival:For babies less than 32 wksGreater than 2% of all live birthsUp to greater than 85% survivalEmphasis on Outcomes:Improvement in ND outcomesInfants less than 26 wks:Approximately 15% with CPAt 11 yrs:25% severe ND disability35% moderate ND disability20% mild ND disabilityOutcomes: no sense in saving these babies if we can’t give them a good chance “normal” lifeMarlow et al. NEJM 2005Anderson et al. JAMA 2003Epicure, 2005
12 Epidemiology: Preterm Infants Emphasis on Outcomes:Infants less than 30 wks25 – 50% cognitive, behavioral, social difficulties requiring special ed. intervention5 – 15% cerebral palsy, severe neuro-sensory impairment or bothOverall:At 8 years of age50% children BW less than 1 kg in special education20% children BW less than 1 kg repeat a grade10 -15% children BW less than 1 kg with spastic motor CPMarlow et al. NEJM 2005Anderson et al. JAMA 2003
13 Typical Injury Patterns: ELGA / VLBW IVHVentriculomegalyWhite matterinjuryPHHGray matter injuryHemorrhageHypoxiaIschemiaLEADS TOVolpe, Neurology of the Newborn, 2008Follett et al, JNeurosci, 2001, 2004Deng et al, PNAS, 2006
14 Evolution of Injury: ELGA / VLBW Local necrosis with congestion or hemorrhageEcho-lucent cysts in periventricular white matterEcholucent cysts – tissue dissolution – 1-3 wksVentriculomegaly – 2-3 monthsVentriculomegaly, cysts disappear, deficient myelin and/or gliosis with collapse of cysts, echo-densities
15 Factors to Consider When Imaging Critically Ill Infants TimingTechniqueTransportCompatibilityAvailabilitySedationGiven the modalities readily available to us and the limitations and difficulties we encounter, we’re going to examine the following (next slide)
16 Ultrasound: Diagnostic Capabilities HemorrhagicHydrocephalusPeriventricular hemorrhaghic infarctionNon-hemorrhagicEchodensitiesEcholucenciesVentricular enlargementEdemaSensitivity much increased with multiple scansEcholucencies – less frequently seen in white matter but much more predicitive of long term clinical morbidity. Most ominous in the first 2 wks of life.Risk for PHH – most prognostic questionLate U/S findings with ventricular enlargement, cystic changes in white matter or hydrocephalus – increased risk of CPLater scans more prognosticEcholucencies strongly assoc with CP more so than MREchodensities freq transientReasons to change from Papile grading system to descriptions.DeVries et al, JPediatric, 2004
20 Ultrasound: Prognostic Capabilities Major abnormalitiesGr 3 IVH, PHI, Cystic PVLPredictive of CP and NM delay at follow upPredictive of impaired cognitive outcome but with less sensitivity and specificityMild abnormalitiesPrediction of CP or cognitive deficits is problematicNot predictive of NORMAL outcomeEl-Dib, M. et al. Am J Perinatol
21 Ultrasound: Prognostic Capabilities Diffuse PVL: low sensitivityMisses greater than 50% diffuse white matter injuryHemorrhage conveys less prognostic info than evidence of white matter damage and PHHCerebellar Injury30 -60% preemies who develop CP had lesions on US during perinatal period
22 Ultrasound: Prognostic Capabilities Recent literaturegr1 and gr2 IVH in infants <26 GA with poorer ND/NC outcomesSignificant assoc. btwn gr 3 – 4 IVH, Cystic PVL, mod- sev ventriculomegaly, and CP at 2 - 9yrs in babies < 1500gPatra, K et al. JPeds, 2006
23 Ultrasound: Prognostic Capabilities Grade 4 IVH and ventriculomegaly strong assoc with MR and neuropsych disorders at yrs in infants <1500gOdds Ratio: 10 fold increase in adverse outcome with above sonographic findings
24 Ultrasound: Limitations Poor contrast for lesions of brain parenchymaLimited field of viewInsensitive for identification of hemorrhage adjacent to boneFair cerebellar viewsOperator dependent
25 Ultrasound: Conclusions ELGAN / VLBW Routine screening <30 wksScreen btwn days80% IVHScreen 36 wks PMAWhite matter injuryDiagnostic utility quite goodPrognostic role limited to more severe injury patternsSerial HUS may increase predictive abiltiy
26 He who joyfully marches to music in rank and file has already earned my contempt. He has been given a large brain by mistake, since for him the spinal cord would suffice.Albert Einstein
28 MRI: ELGAN / VLBW T1 T2 DWI/ DTI/ FA / tractography / fMRI Volumetrics Early MRICorrected term (40 – 42 wks CGA)Utility in preterm brainUtility in term corrected brainAbnormalities of myelination of PLIC correlate very closely with cerebral palsyT1/t2 – subacute injuryDTI/DWI – acute injuryT.M. O’Shea et al. EarlyHumDev, 2005.
29 MRI: ELGAN /VLBW Superior evaluation of: Identifies: Brain structuresGray / white matterBrain stem / posterior fossaIdentifies:More abnl findings 1st wk of lifeMore hemorrhagic lesionsMore extensive cystsSubtle / Diffuse white matter injuryPrognostic benefit:CPLearning disabilitiesBehavioral problems
31 MRI : Prognostic Capabilities Woodward et al. Neonatal MRI to PredictNeurodevelopmental Outcomes in Preterm Infants.NEJM, August 2006.167 infants < 30 wksAt 2 yrs17 % severe cognitive delay10 % severe psychomotor delay10% CP11% neurosensory impairment21% moderate – severe cerebral white matter injuryAttempt to correlate clinical outcomes from children 2 yrs and MRI findings at term (PMA)New Zealand and Australia
33 MRI: Prognostic Capabilities Cont…d Majority of preemies haveLoss of volumeCystic abnormalityEnlarged ventriclesThinning of the corpus callosumDelayed myelinationCan these term findings be associated with definitive outcomes at 2yr, 4yrs, 6yrs, etc
34 Study Results 28% no white matter injury 5% mild white matter injury 17% moderate white matter injury6% severe white matter injuryCorrelation of MRI at term with outcome at 2 yrs of age (corrected)More signif the white matter injury, the greater the neuro dev impairmentNormal or mild MRI result = free of severe impairments at 2yrs.Mod –severe MRI white matter injury – severe neurodev deficitsMost common impairment noted severe cognitive delay (approx 20% of kids scored more than 6mo below corrected age)
35 The chief function of the body is to carry the brain around. Thomas A. Edison
37 CT Scan: ELGAN / VLBW Good imaging modality Limited use due to: HemorrhageCerebral volume / Ventricles / Extra-axial spaceBonesLimited use due to:Ionizine radiation / risk of future malignancyCognitive impairmentCorrelations btwn clinical outcome and image results weakIonizing radiation – o.1% risk life long fatal malignancy from head CT at age 12 months estimatedRisk of development of brain tumor found to be 10 fold higher in infants exposed to cranial irradiation under 5 mo. In comparison to over 7 mo.
38 MRI vs Ultrasound vs CT in the ELGAN/VLBW: Conclusion Ultrasound EarlyMRI LaterUltrasound earlyMRI laterForget the CT Scan
39 Imaging the Term Infant Hypoxic Ishcemic EncephalopathyNeonatal StrokeArterial Ischemic StrokeCerebral Venous ThrombosisIntracerebral HemorrhagePeriventricular LeukomalaciaIntraventricular HemorrhageCongenital Anomalies
40 Ultrasound: Term Infant Not ubiquitously helpfulPoor parenchymal evaluationPoor anatomic viewsPoor for strokeGood for IVH evaluationDoppler viewsVascularHydrocephalus vs VentriculomegalyRI = (systolic ACA blood flow – diastolic ACA blood flow)diastolic ACA blood flowMarker of acute edema, increased ICP
41 CT Scan: Term Infant Significant findings Global picture of injury CalcificationsHemorrhageLow attenuation in basal ganglia and thalamusGlobal picture of injuryExtremely fastEmergent situationLimited use due to:Risk of future malignancyRisk of future cognitive impairmentUsu in infant with midline shift on HUS who needs emergent neurosurg intervention
42 MRI: Term Infant No ionizing radiation Multi-planar imaging More sensitive and specific for CNS evaluation than CT or USGrey matterWhite matterModality of choice
43 MRI: Hypoxic Ischemic Encephalopathy Water and the brainT1 – 7 daysT2 – 7 daysDWI: one of the earliest indicators of tissue injury (within hours) – best 2 – 4 daysNo ionizing radiationVolumetric data of sensorimotor and mid-temporal cortices are assoc with full scale verbal and performance IQ scoresPLIC most reliable region compared to histopathEvolving patterns of injury over timeMR Spect: functional eval - creatinine and lactate peaks>50% basal ganglia and thalamic region injury
44 MRI: Pattern of Brain Injury 2 main typesBasal Ganglia-ThalamusAcute near total asphyxiaCP / cognitive injury readily apparentWatershed PredominantProlonged partial asphyxiaAnt – Mid cerebral arteryPost –Mid cerebral arteryChildhood symptoms / Deficits at 30 mo.
45 MRI: HIE Prognostic Capabilities Neurodevelopmental handicap at 1-2 yrs of age if:Basal ganglia or thalamic abnormality50 – 94% with CP, mental retardation, seizure disorderWell established
46 I was taught that the human brain was the crowning glory of evolution so far, but I think it's a very poor scheme for survival.Kurt Vonnegut
48 MR Spectroscopy: Term Infant Non-invasive in vivo biochemical analysisCellular metabolic informationDetection of biochemical changes before morphological changes apparentNAALactateCreatineCholinePrognosisEarly H-MRS studies promising