DESCRIPTION: Study In the US military, it is estimated that roughly 20% of the deployed force suffered a head injury1 in the wars in Iraq and Afghanistan, 83.3% of whom endured a mild, uncomplicated TBI or concussion2,3. The long term impact of these injuries is just beginning to be appreciated. Many of these service members are young males, 20-30 years old who have decades of life to live with the complex and often debilitating impact of war-time brain injury. The total lifetime health care costs are largely unknown. Although substantial effort has been placed on trying to better understand this type of injury, much research has been forced to rely largely on self- reporting4-11, retrospective medical records review 12-16, or evaluations of only later stages of injury17, 18. No study to date has prospectively followed active-duty US military from injury to long term outcome with advanced MR imaging and clinical evaluation. The overall goal is to investigate long-term advanced MR imaging measures and clinical outcome of concussive traumatic brain injury (TBI) sustained during deployment in US military personnel. We will relate these findings to prospectively acquired longitudinal imaging and clinical data from the acute/sub-acute, and early chronic stages following concussion collected on these patients as part of previous collaborative efforts. We hypothesize that early clinical and imaging measures will offer predictive insight into late stage clinical outcome. Study Design: As part of previous collaborative efforts, we have successfully completed early prospective, longitudinal studies enrolling active-duty US military at 0-7 days (median 4), 0-30 days (median 8), and 0-90 days (median 14) post-injury19-21 where early advanced MR imaging and clinical data were collected. In total, 591 subjects were enrolled through these efforts; 54% TBI, 46% control. We propose to re-examine control and TBI subjects now 5-7 years post-injury and compare their current clinical and imaging presentation with the previously acquired longitudinal data. We believe that this population offers a unique opportunity to rigorously evaluate the long term impact of war-time concussive TBI. Aim #1: To explore long-term evolution of neurological, neuropsychological, and psychiatric effects of mild- concussive TBI in US military personnel by analyzing clinical outcome data to be collected 5-7 years post- injury and previously prospectively acquired early clinical data. Aim #2: To quantify the relationship between imaging biomarkers of brain injury from early and long-term advanced MRI data in US military personnel with mild-concussive TBI by analyzing DTI data acquired 5-7 years post injury and previously collected acute, sub-acute and early-chronic DTI data. Aim #3: To develop a predictive model from combined acute, sub-acute, and early-chronic clinical and imaging data for long-term outcomes following mild-concussive TBI in US military personnel.

PUBLIC HEALTH RELEVANCE: The overall goal is to investigate long-term advanced MR imaging measures and clinical outcome of concussive traumatic brain injury (TBI) sustained during deployment in US military personnel. We will relate these findings to prospectively acquired longitudinal imaging and clinical data from the acute/sub-acute, and early chronic stages following concussion collected on these patients as part of previous collaborative efforts. We hypothesize that early clinical and imaging measures can be used to predict 5-7 year late stage clinical outcome which will offer important insight into the long term impact of war-time mild TBI thereby guiding new recommendations for clinical management and therapeutic intervention.