Neuroimaging in the Neonate Debra B. Selip, MD Fetal and Neonatal Medicine Center and Division of...

Neuroimaging in the Neonate

Debra B. Selip, MDFetal and Neonatal Medicine Center

and

Division of NeonatologyRush University Medical Center

March 4, 2011

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

Neuroimaging Modalities Xray Ultrasound CT scan MRI

• T1

• T2

• DWI / DTI / FA / Tractography

• MR Spectroscopy NM Scans

• SPECT

• PET

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

Prognostic Concerns

Clinical evaluation insufficient for prognostication

Cerebral Palsy? School Performance?

• Neurocognitive & neurodevelopmental disabilities

• Behavioral disabilities

Role for neuroimaging?

2 Types of Neonates

Preterm Infants• Periventricular Leukomalacia

• Intraventricular Hemorrhage

• Post-hemorrhaghic Hydrocephalus

• Periventricular Hemorrhagic Infarction

• Intraparenchymal Hemorrhage

• Cortical and Deep Gray Matter Injury

2 Types of Neonates

Full term Infant• Stroke

• Intracerebral Hemorrhage

• Periventricular Leukomalacia

• Intraventricular Hemorrhage

• Congenital Anomalies

• Cortical and Deep Gray Matter Injury

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

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

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

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

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

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

Factors to Consider When Imaging Critically Ill Infants

Timing Technique Transport Compatibility Availability Sedation

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

El-Dib, M. et al. Am J Perinatol. 2010.

Grades of IVH – grade 1 to 4


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



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


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


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

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

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

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

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.

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

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

Woodward et al. NEJM. Aug 2006

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

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

The chief function of the body is to carry the brain around.

Thomas A. Edison

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

MRI vs Ultrasound vs CT in the ELGAN/VLBW: Conclusion

Ultrasound Early

MRI Later

Forget the CT Scan

Imaging the Term Infant

Hypoxic Ishcemic Encephalopathy Neonatal Stroke

• Arterial Ischemic Stroke

• Cerebral Venous Thrombosis

• Intracerebral Hemorrhage Periventricular Leukomalacia Intraventricular Hemorrhage Congenital Anomalies

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

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

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

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

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.

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

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

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

Summary

Appropriate modality for particular investigation Pre-term Imaging

• US

• MRI

• MR Spect?

Full-term Imaging• CT

• MRI

• MR Spect?

Neuroimaging in the Neonate Debra B. Selip, MD Fetal and Neonatal Medicine Center and Division of...

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