Support is requested to study methods using magnetic resonance (MR) and near infrared spectroscopy (NIRS) that will reliably enable the clinician to predict neurological outcome after perinatal asphyxia. Clinical and laboratory indicators of outcome that have been used to date, such as umbiliCal cord pH and Apgar scores, have proven unreliable. Our preliminary work indicates that standard MR imaging can detect distinctive patterns of damage from perinatal asphyxia by the third day of life and MR spectroscopy can detect injury by the second day of life. Perfusion MR imaging, blond-brain barrier imaging, and diffusion imaging seem to show damage even earlier. NIRS can detect the level of hemoglobin oxygenation and mitochondrial function in the immediate neonatal period. The hypothesis of this proposal are that abnormal T1 and T2 relaxation times, abnormal cerebral perfusion abnormal proton diffusion in the brain, and blood-brain barrier breakdown (as detected by MRI), lactate accumulation (as detected by MRS), and abnormal oxygenation and mitochondrial funCtion (as detected by NIRS) are parameters that will correlate with the degree of neurodevelopmental dysfunction seen later In life. We will use the data obtained in this study to define predictors of outcome in term infants who have suffered perinatal hypoxia-ischemia. These predictors will be derived from a correlation of MR and NIRS parameters (from perfusion contrast and diffusion MR imaging, proton MR spectroscopy, and NIRS performed in the first few days of life) with sophisticated neurodevelopmental testing performed at ages 3 months, 12 months, and 30 months. A sophisticated patient tracking mechanism will be utilized to maintain the cohort of babies for long term follow-up (8-12 years) in order to provide an accurate assessment of neurological, psychological and intellectual outcomes. In addition, the MR and NIRS parameters will be correlated with those in Project 2 in order to aid interpretation with respect to pathologic substrates. This approach should enable investigators to study mechanisms of ischemic damage, develop rational therapies aimed at reducing such damage, and more accurately determine those patients in need of such therapies, those at risk for abnormal neurodevelopmental outcome.
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