Brain Metabolism and Outcome Following TBI in Children

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DESCRIPTION (provided by applicant): Although traumatic brain injury (TBI) is the leading cause of death and acquired disability in North American children, the pathophysiological processes involved in childhood TBI are poorly understood. We have recently shown that neurometabolite markers of brain cellular injury-N-acetylaspartate (NAA) and choline (Cho) measured remote from the locus of TBI by non-invasive magnetic resonance spectroscopy (MRS, predict long-term cognitive outcome in adults. Furthermore, unique patterns of neurometabolite changes emerged in gray vs. white matter, suggesting differing processes affecting neuronal soma and axons. Although spectroscopic abnormalities are seen in children after TBI, the specific relationships between these sensitive markers of injury and cognitive function are yet to be determined. Magnetic resonance spectroscopic imaging (SI) provides a unique, time-efficient means to simultaneously quantify these markers throughout the brain. The goals of this research are (1) to validate SI as a diagnostic tool for accurate in vivo assessment of regional TBI severity, and (2) to increase our understanding of the evolution of pathophysiological events after TBI and their relation to cognitive outcome in children. By elucidating the relationship between age, TBI severity, and cognitive outcome, this research may help to improve outcome prediction and facilitate treatment of childhood TBI. Since MRS provides a direct measure of the underlying cellular injury associated with TBI, it may elucidate the pathophysiological mechanism in developing brain. Hence, it may form the basis for a powerful outcome measure for basic research and clinical trials. Specific Aims 1 through 3 confirm and extend our IH-MRS studies of adults with TBI to injured children. We propose to characterize, in children, neurometabolite evidence of neuronal injury after TBI (Aim 1), as well as the relationship between selected neurometabolite concentrations and overall cognitive performance (Aim 2). Age effects will receive special attention (Aim 3). Exploratory Aims 4 and 5 examine regionally specific neurometabolite data captured by Sl to characterize noninvasively the anatomic distribution of brain cellular injury changes (Aim 4). We also propose to investigate whether cellular injury changes in diverse brain regions have different cognitive sequelae in children (Aim 5). These analyses will facilitate an understanding of the nature and significance of regional variation in neurometabolite changes, and hence, the clinical heterogeneity of TBI in children.