Quantitative MRI and 1H-MRS in Traumatic Brain Injury

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Mild traumatic brain injury (MTBI) and post concussion syndrome (PCS) are acknowledged as highly significant public health problems affecting over 1.2 million Americans in both civilian and combat military sectors at a cost exceeding $17 billion annually. Troubling, therefore, is the fact that conventional clinical radiological tools such as computed tomography (CT) and magnetic resonance (MR) imaging (MRI) often fail, to detect brain abnormalities ensuing from MTBI that can account for the array of physical, cognitive and emotional/behavioral symptoms defining PCS. Since there are no good animal models for MTBI, the current teaching is that in humans, PCS pathology is the result of diffuse axonal injury (DAI) occurring predominantly in stereotypical locations including the gray-white junction, corpus callosum, and midbrain. Contrary to this commonly accepted principle, we hypothesize (Central Hypothesis) that the primary site of injury in MTBI is the thalamus. This hypothesis is based upon the preliminary results we have gathered. This data is supported by: (1) literature demonstrating neuropathological injury to this structure; and (2) the ability to ascribe a multitude of post concussive symptoms to one site. Thalamic damage results in structural and metabolic abnormalities that can be quantified by MR (diffusion kurtosis, magnetic field correlation, blood perfusion, and volumetric measures) and MR spectroscopy (MRS) and is responsible for PCS. To test this hypothesis we propose three Specific Aims: Specific Aim 1: to establish, within the first month after MTBI, with quantitative MR at high-field (3T), evidence of microstructural, perfusional, and biochemical thalamic abnormalities, in 20 new patients accrued annually, compared with age/sex matched controls. Specific Aim 2: to associate post concussive symptoms and a battery of neuropsychological tests with structural and biochemical metrics. Specific Aim 3: to serially follow up each patient annually to enable identification and validation of quantitative predictive metrics of clinical outcome in MTBI. Health Relevance: This research is designed to: (1) improve our diagnostic acumen and understanding of the MTBI "epidemic"; (2) provide objective metrics to detect and quantify MTBI; (3) enable the prediction of outcome; and (4) contribute new insights into the pathophysiology of MTBI that will potentially result in better treatment for these patients.