The long-term objective of this project is improved evaluation of Traumatic Brain Injury (TBI) using advanced MR neuroimaging methods. TBI represents a major public health problem for which there are currently no objective measures that are able to quantify the severity of injury, or to indicate possible outcomes. Previous studies have shown that Magnetic Resonance Spectroscopy can detect widespread metabolic changes in the brain that correlate with the degree of injury, even in the absence of significant MRI findings. For mild TBI subjects, which represents the largest group of these patients and the most difficult to evaluate, these diffuse metabolic abnormalities may be small in magnitude, though widespread, while it is also known that some brain regions are more susceptible to injury and may have more focal abnormalities, particularly with more severe injury. Therefore, it is hypothesized that improved characterization of this type of brain injury will be obtained by using a) improved detection sensitivity and acquisition from a wide region of the brain, and b) analysis of both focal and diffuse multiparametric metabolic abnormalities, in comparison with normal values. This pilot study will use volumetric proton MR Spectroscopic Imaging (MRSI) at 3 Tesla using phased-array detection, for characterization of metabolic changes associated with mild and moderate closed-head TBI. Measurements will include N-Acetylaspartate and choline, metabolic markers known to be sensitive to neuronal dysfunction and membrane turnover. Results will be correlated with findings from structural MRI, initial clinical assessments, and outcome evaluations, including results of neuropsychological testing. MRSI processing methods will incorporate MRI information to enable metabolite analysis by brain region and tissue type, as well as voxel-based comparisons with normal values. Quantitative neuroimaging measures will be developed that will characterize: 1) which brain locations experience greatest MR-detected metabolic and structural changes; 2) the spatial extent and the degree of metabolic alteration; and 3) which clinical and MR imaging measures best correlate with clinical outcome at 6 months post injury. It is hypothesized that the improved sensitivity and spatial coverage of the spectroscopic measurement and analysis methods will enable improved characterization of mild and moderate injury, and that the metabolic neuroimaging methods will be more sensitive than MRI for evaluation of this brain injury. Relevance of this research: Improved imaging assessment of metabolic changes associated with diffuse brain injury will guide treatment and patient management decisions following brain trauma, as well as providing expectations for long-term consequences of the injury. ? ? ?