Neuroimaging in the Neonate

1. Neuroimaging in the Neonate Debra B. Selip, MD Fetal and Neonatal Medicine Center and Division of Neonatology Rush University Medical Center March 4, 2011

2. 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

3. Neuroimaging Modalities • Xray • Ultrasound • CT scan • MRI • T1 • T2 • DWI / DTI / FA / Tractography • MR Spectroscopy • NM Scans • SPECT • PET

4. 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

5. Prognostic Concerns • Clinical evaluation insufficient for prognostication • Cerebral Palsy? • School Performance? • Neurocognitive & neurodevelopmental disabilities • Behavioral disabilities • Role for neuroimaging?

6. 2 Types of Neonates • Preterm Infants • Periventricular Leukomalacia • Intraventricular Hemorrhage • Post-hemorrhaghic Hydrocephalus • Periventricular Hemorrhagic Infarction • Intraparenchymal Hemorrhage • Cortical and Deep Gray Matter Injury

7. 2 Types of Neonates • Full term Infant • Stroke • Intracerebral Hemorrhage • Periventricular Leukomalacia • Intraventricular Hemorrhage • Congenital Anomalies • Cortical and Deep Gray Matter Injury

8. 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

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 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 disability Marlow et al. NEJM 2005 Anderson et al. JAMA 2003 Epicure, 2005

12. 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 2005 Anderson et al. JAMA 2003

13. Typical Injury Patterns: ELGA / VLBW • IVH • Ventriculomegaly • White matter injury • PHH • Gray matter injury • Hemorrhage • Hypoxia • Ischemia LEADS TO Volpe, Neurology of the Newborn, 2008 Follett et al, JNeurosci, 2001, 2004 Deng et al, PNAS, 2006

14. Evolution of Injury: ELGA / VLBW Local necrosis with congestion or hemorrhage Echo-lucentcysts in periventricular white matter Ventriculomegaly, cysts disappear, deficient myelin and/or gliosis with collapse of cysts, echo-densities

15. Factors to Consider When Imaging Critically Ill Infants • Timing • Technique • Transport • Compatibility • Availability • Sedation

16. 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

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

18. Grades of IVH – grade 1 to 4 El-Dib, M. et al. Am J Perinatol. 2010.

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

20. 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.

21. 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

22. 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

23. 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

24. 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

25. 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

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 MRI • Corrected term (40 – 42 wks CGA) • Utility in preterm brain • Utility in term corrected brain T.M. O’Shea et al. EarlyHumDev, 2005.

29. 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

31. MRI : Prognostic Capabilities Woodward et al. Neonatal MRI to Predict Neurodevelopmental 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

32. Woodward et al. NEJM. Aug 2006

33. 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

34. 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

35. The chief function of the body is to carry the brain around. Thomas A. Edison

37. 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

38. MRI vs Ultrasound vs CT in the ELGAN/VLBW: Conclusion Ultrasound Early MRI Later Forget the CT Scan

39. Imaging the Term Infant • Hypoxic Ishcemic Encephalopathy • Neonatal Stroke • Arterial Ischemic Stroke • Cerebral Venous Thrombosis • Intracerebral Hemorrhage • Periventricular Leukomalacia • Intraventricular Hemorrhage • Congenital Anomalies

40. 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

41. 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

42. 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

43. 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 data of sensorimotor and mid-temporal cortices are assoc with full scale verbal and performance IQ scores

44. 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.

45. MRI:HIEPrognosticCapabilities • Neurodevelopmental handicap at 1-2 yrs of age if: • Basal ganglia or thalamic abnormality • 50 – 94% with CP, mental retardation, seizure disorder • Well 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 analysis • Cellular metabolic information • Detection of biochemical changes before morphological changes apparent • NAA • Lactate • Creatine • Choline • Prognosis • Early H-MRS studies promising

49. Summary • Appropriate modality for particular investigation • Pre-term Imaging • US • MRI • MR Spect? • Full-term Imaging • CT • MRI • MR Spect?