Next Generation Imaging Biomarkers for Mild Traumatic Brain Injury

Once considered to be a fully reversible insult of little consequence, mild traumatic brain injury (mTBI) is now recognized as a silent epidemic. Recent evidence suggests that mTBI is followed by a period of increased cerebral vulnerability (ICV) that can persist beyond the time at which patients are typically cleared to return to pre-injury activity. A subsequent insult during this period is thought to result in exacerbated outcomes with repeated mTBI associated with cumulative & chronic neurological impairments & the development of neurodegenerative diseases including chronic traumatic encephalopathy & Alzheimer’s disease. As such, it is important to identify accurate & reliably biomarkers of the ICV that follows mTBI so that appropriate & informed medical decisions can be made, particularly when determining a return to pre-injury activity. Neuroimaging holds great promise in this regard. Recently, chemical exchange saturation transfer (CEST) imaging has been introduced as a method of interrogating molecular species such as glutamate & myo-inositol. As mTBI induced abnormalities in these metabolites are thought to contribute to the ICV that follows injury, this research program will examine the hypothesis that CEST is a potentially powerful biomarker of mTBI. Using a state-of-the-art preclinical MRI, this innovative research program will investigate the potential of CEST to quantitatively assess glutamate & myo-inositol levels in an experimental model of mTBI. Secondly, these biomarkers will be used to inform the timing of subsequent injuries to ameliorate the exacerbated outcomes seen in repeated mTBI. Finally, these methods will be translated to the clinical setting, using an ultra-high field 7T MRI. Significance: This proposal will investigate the effectiveness of CEST as a biomarker of mTBI & provide important insights into the ICV that follows injury to better inform return to play decisions & mitigate the adverse outcomes that can follow repeated mTBI.