Despite many advances in the care and survival of newborns, neonatal encephalopathy remains a significantpublic health problem, affecting more than 1 in 1000 live births. The prognosis and optimal therapy fornfants with moderate neonatal encephalopathy remains uncertain, as these depend on the severity of brainnjury and the ability of the brain to recover from the injury. Therapeutic interventions have beendisappointing, partially because it requires years to determine their effects on neurodevelopmental outcome.Preliminary data suggest that white matter may be affected secondarily (with gray matter injury beingprimary) and that patients with injury to the cerebral cortex show more substantial recovery than those withinjury to the white matter pathways leading to and from those cortical areas. We propose to use newmagnetic resonance techniques, high angular resolution diffusion imaging (HARDI, a robust way to learnabout injury to brain microstructure, such as white matter pathways) and spectroscopic imaging (MRSI, arobust way to look at brain biochemistry) to evaluate white matter pathways involved in motor and visualfunction. An initial MR study will performed day 5 after injury, the best time to assess both maximal extent ofinitial injury and presence of secondary white matter injury. A second MR study will be performed at age 3months to determine the extent of repair/recovery of the white matter pathways; this will be accomplished byassessing microstructural and metabolic markers of both the integrity of the pathways and the degree ofrepair. We suggest that the 3 month exam will ultimately be an optimal time to judge the effects of earlyinterventions, some of which are being investigated in other projects of this P50. The children will beexamined with particular attention to motor and visual function at ages 3 months, 12 months, and 30 months.Statistical analyses will be performed to determine whether the degree of repair/recover, as assessed by MRtechniques on the 3 month exam, gives added value regarding neurodevelopmental outcome compared withthe extent/severity of injury, as assessed on the exam at age 5 days. We will also develop models to predictoutcome, based on clinical neonatal exams, laboratory values, and MRI exams.
TO PUBLICHEALTH: Achieving these goals will ultimately result in improved care and outcome in encephalopathicneonates, and potential therapies aimed at the repair process after neonatal ischemic events.
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