neuroimaging in the neonate debra b. selip, md fetal and neonatal medicine center and division of...
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Neuroimaging in the Neonate
Debra B. Selip, MDFetal and Neonatal Medicine Center
and
Division of NeonatologyRush University Medical Center
March 4, 2011
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Neuroimaging in the Neonate
Wide array of imaging modalities readily available
Expanding and rapidly changing body of literature examining appropriate imaging methods and prognostic applications
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Neuroimaging Modalities Xray Ultrasound CT scan MRI
• T1
• T2
• DWI / DTI / FA / Tractography
• MR Spectroscopy NM Scans
• SPECT
• PET
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Why Image?
2 Roles:
• Diagnose brain injury in at risk newborns
• Improve and provide acute medical management/interventions
• Detect lesions associated with long-term neurodevelopmental disability•Appropriate prognosis/predictions
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Prognostic Concerns
Clinical evaluation insufficient for prognostication
Cerebral Palsy? School Performance?
• Neurocognitive & neurodevelopmental disabilities
• Behavioral disabilities
Role for neuroimaging?
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2 Types of Neonates
Preterm Infants• Periventricular Leukomalacia
• Intraventricular Hemorrhage
• Post-hemorrhaghic Hydrocephalus
• Periventricular Hemorrhagic Infarction
• Intraparenchymal Hemorrhage
• Cortical and Deep Gray Matter Injury
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2 Types of Neonates
Full term Infant• Stroke
• Intracerebral Hemorrhage
• Periventricular Leukomalacia
• Intraventricular Hemorrhage
• Congenital Anomalies
• Cortical and Deep Gray Matter Injury
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Outline Preterm infant: ELGAN / VLBW
• Epidemiology• Neuroimaging modalities• Indications for use• Findings and clinical correlates• Conclusions
Term• Epidemiology• Neuroimaging modalities• Indications for use• Findings and clinical correlates• Conclusions
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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
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Epidemiology: Preterm Infant ELGAN/ VLBW:
• number preterm infants and survival:• For babies less than 32 wks
• Greater than 2% of all live births
• Up to greater than 85% survival
• Emphasis on Outcomes:• Improvement in ND outcomes
• Infants less than 26 wks:• Approximately 15% with CP
• At 11 yrs:
• 25% severe ND disability
• 35% moderate ND disability
• 20% mild ND disabilityMarlow et al. NEJM 2005Anderson et al. JAMA 2003Epicure, 2005
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Epidemiology: Preterm Infants Emphasis on Outcomes:
• Infants less than 30 wks• 25 – 50% cognitive, behavioral, social difficulties
requiring special ed. intervention• 5 – 15% cerebral palsy, severe neuro-sensory
impairment or both Overall:
• At 8 years of age• 50% children BW less than 1 kg in special education • 20% children BW less than 1 kg repeat a grade• 10 -15% children BW less than 1 kg with spastic motor
CP
Marlow et al. NEJM 2005Anderson et al. JAMA 2003
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Typical Injury Patterns: ELGA / VLBW
Hemorrhage Hypoxia
Ischemia
IVHVentriculomegalyWhite matter injury PHHGray matter injury
LEADS TO
Volpe, Neurology of the Newborn, 2008Follett et al, JNeurosci, 2001, 2004Deng et al, PNAS, 2006
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Evolution of Injury: ELGA / VLBW
Local necrosis with congestion or hemorrhage
Ventriculomegaly, cysts disappear, deficient myelin and/or gliosis with collapse of cysts, echo-densities
Echo-lucent cysts in periventricular white matter
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Factors to Consider When Imaging Critically Ill Infants
Timing Technique Transport Compatibility Availability Sedation
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Ultrasound: Diagnostic Capabilities
Hemorrhagic• Hydrocephalus
• Periventricular hemorrhaghic infarction Non-hemorrhagic
• Echodensities
• Echolucencies
• Ventricular enlargement
• Edema
• Hydrocephalus Sensitivity much increased with multiple scans
DeVries et al, JPediatric, 2004
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El-Dib, M. et al. Am J Perinatol. 2010.
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Grades of IVH – grade 1 to 4
El-Dib, M. et al. Am J Perinatol. 2010.
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El-Dib, M. et al. Am J Perinatol. 2010.
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Ultrasound: Prognostic Capabilities
Major abnormalities• Gr 3 IVH, PHI, Cystic PVL
• Predictive of CP and NM delay at follow up
• Predictive of impaired cognitive outcome but with less sensitivity and specificity
Mild abnormalities• Prediction of CP or cognitive deficits is problematic
• Not predictive of NORMAL outcome
El-Dib, M. et al. Am J Perinatol. 2010.
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Ultrasound: Prognostic Capabilities
Diffuse PVL: low sensitivity• Misses greater than 50% diffuse white matter injury
Hemorrhage conveys less prognostic info than evidence of white matter damage and PHH
Cerebellar Injury
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Ultrasound: Prognostic Capabilities
Recent literature
• gr1 and gr2 IVH in infants <26 GA with poorer ND/NC outcomes
• Significant assoc. btwn gr 3 – 4 IVH, Cystic PVL, mod- sev ventriculomegaly, and CP at 2 - 9yrs in babies < 1500g
Patra, K et al. JPeds, 2006
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Ultrasound: Prognostic Capabilities
Grade 4 IVH and ventriculomegaly strong assoc with MR and neuropsych disorders at 2 - 9 yrs in infants <1500g
Odds Ratio: 10 fold increase in adverse outcome with above sonographic findings
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Ultrasound: Limitations
Poor contrast for lesions of brain parenchyma
Limited field of view• Insensitive for identification of hemorrhage adjacent to
bone
• Fair cerebellar views
Operator dependent
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Ultrasound: Conclusions ELGAN / VLBW
Routine screening <30 wks Screen btwn 7 -14 days
• 80% IVH
Screen 36 wks PMA• White matter injury
Diagnostic utility quite good Prognostic role limited to more severe injury
patterns
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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
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MRI: ELGAN / VLBW
T1 T2 DWI/ DTI/ FA / tractography / fMRI Volumetrics Early MRI Corrected term (40 – 42 wks CGA) Utility in preterm brain Utility in term corrected brain
T.M. O’Shea et al. EarlyHumDev, 2005.
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MRI: ELGAN /VLBW Superior evaluation of:
• Brain structures• Gray / white matter• Brain stem / posterior fossa
Identifies:• More abnl findings 1st wk of life• More hemorrhagic lesions• More extensive cysts• Subtle / Diffuse white matter injury
Prognostic benefit:• CP• Learning disabilities• Behavioral problems
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MRI : Prognostic Capabilities
Woodward et al. Neonatal MRI to PredictNeurodevelopmental Outcomes in Preterm Infants.
NEJM, August 2006. 167 infants < 30 wks At 2 yrs
• 17 % severe cognitive delay
• 10 % severe psychomotor delay
• 10% CP
• 11% neurosensory impairment 21% moderate – severe cerebral white matter injury
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Woodward et al. NEJM. Aug 2006
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MRI: Prognostic Capabilities Cont…d
Majority of preemies have• Loss of volume
• Cystic abnormality
• Enlarged ventricles
• Thinning of the corpus callosum
• Delayed myelination
Can these term findings be associated with definitive outcomes at 2yr, 4yrs, 6yrs, etc
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Study Results
28% no white matter injury 5% mild white matter injury 17% moderate white matter injury 6% severe white matter injury
Correlation of MRI at term with outcome at 2 yrs of age (corrected)• More signif the white matter injury, the greater the
neuro dev impairment
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The chief function of the body is to carry the brain around.
Thomas A. Edison
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CT Scan: ELGAN / VLBW Good imaging modality
• Hemorrhage
• Cerebral volume / Ventricles / Extra-axial space
• Bones
Limited use due to:• Ionizine radiation / risk of future malignancy
• Cognitive impairment
Correlations btwn clinical outcome and image results weak
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MRI vs Ultrasound vs CT in the ELGAN/VLBW: Conclusion
Ultrasound Early
MRI Later
Forget the CT Scan
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Imaging the Term Infant
Hypoxic Ishcemic Encephalopathy Neonatal Stroke
• Arterial Ischemic Stroke
• Cerebral Venous Thrombosis
• Intracerebral Hemorrhage Periventricular Leukomalacia Intraventricular Hemorrhage Congenital Anomalies
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Ultrasound: Term Infant
Not ubiquitously helpful • Poor parenchymal evaluation
• Poor anatomic views
• Poor for stroke Good for IVH evaluation Doppler views
• Vascular
• Hydrocephalus vs Ventriculomegaly• RI = (systolic ACA blood flow – diastolic ACA blood
flow) diastolic ACA blood flow
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CT Scan: Term Infant
Significant findings • Calcifications
• Hemorrhage
• Low attenuation in basal ganglia and thalamus Global picture of injury Extremely fast
• Emergent situation Limited use due to:
• Risk of future malignancy
• Risk of future cognitive impairment
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MRI: Term Infant
No ionizing radiation Multi-planar imaging More sensitive and specific for CNS
evaluation than CT or US• Grey matter
• White matter
Modality of choice
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MRI: Hypoxic Ischemic Encephalopathy
Water and the brain T1 – 7 days T2 – 7 days DWI: one of the earliest indicators of tissue
injury (within hours) – best 2 – 4 days No ionizing radiation Volumetric dataVolumetric data of sensorimotor and mid-
temporal cortices are assoc with full scale verbal and performance IQ scores
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MRI: Pattern of Brain Injury
2 main types• Basal Ganglia-Thalamus
• Acute near total asphyxia
• CP / cognitive injury readily apparent
• Watershed Predominant • Prolonged partial asphyxia
• Ant – Mid cerebral artery
• Post –Mid cerebral artery
• Childhood symptoms / Deficits at 30 mo.
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MRI: HIE Prognostic Capabilities
Neurodevelopmental handicap at 1-2 yrs of age if:• Basal ganglia or thalamic abnormality
• 50 – 94% with CP, mental retardation, seizure disorder
Well established
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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
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MR Spectroscopy: Term Infant Non-invasive in vivo biochemical analysis Cellular metabolic information Detection of biochemical changes before
morphological changes apparent• NAA• Lactate• Creatine• Choline
Prognosis• Early H-MRS studies promising
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Summary
Appropriate modality for particular investigation Pre-term Imaging
• US
• MRI
• MR Spect?
Full-term Imaging• CT
• MRI
• MR Spect?
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