Molecular Neurodevelopment: An In Vivo 31P-1H MRSI Study

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The goal of this project is to acquire a gender- balanced, neurodevelopmental 31P and 1H magnetic resonance spectroscopic imaging (31P-1H MRSI) molecular and metabolic normative database from a representative population of normal children and adolescents ages 6-18 years. The molecular/metabolic values for each volume of interest (voxel) will be correlated with the percent grey matter, white matter and cerebral spinal fluid (CSF) in the same voxel. The individual voxels will include the (right and left) prefrontal cortex, superior temporal cortex, inferior parietal cortex, occipital cortex, basal ganglia, centrum semiovale and thalamus. These areas are chosen so as to include areas of primary sensory (occipital and part of superior temporal cortices), heteromodal association (prefrontal, inferior parietal, and part of superior temporal cortices), subcortical grey (basal ganglia and thalamus) and white matter (centrum semiovale). Examining these areas as a function of age and gender will enable us to determine the effects of normal neurodevelopment on the molecular/metabolic measures of brain areas with different functions. 31P MRS provides measures of membrane phospholipid and high-energy phosphate metabolism and 1H MRS provides additional measures of glutamate, glutamine, taurine, N-acetylaspartate (NAA), a potential marker of neuronal functional integrity, and myo- inositol, a potential glial marker. Subjects will have a standardized neurodevelopmental test battery to assure the cohort is representative of normal cognitive development, and will have yearly pediatric physical examinations, including Tanner staging. The standardized neurodevelopmental test battery will be completed at entry, 2, and 4 years. Longitudinal 31P-1H MRSI and single voxel 1H MRS follow-up of the subjects yearly for 4 years after entry into study will be used to generate neurodevelopmental curves for brain/metabolic measures.