RSHI cohort. Participants were 42 male football players on the University of Rochester football team [National Collegiate Athletic Association (NCAA) division III], enrolled over the course of three seasons (2011, 2012, and 2013). Three participants were lost to follow-up, and one participant lacked field map correction scans, yielding 38 complete datasets (mean age, 19.8; median, 20). All of the players sustained repetitive head impacts across the season, but only 2 of the 38 sustained clinically defined concussion/mTBI. For all participants in the RSHI cohort, MRI scanning was carried out 2 weeks before the start of the season and within 1 week after completion of the season. To record the inertial loading sustained by the players’ brains throughout the season of play, each player wore a helmet-mounted accelerometer that measured linear and rotational acceleration throughout all practices and games. Full details regarding helmet accelerometers to measure head impacts have been previously described (24), including the derivation of rotational acceleration via the accelerometer data. In brief, each athlete was outfitted with a Riddell Revolution IQ helmet (Riddell Corporation, Elyria, OH) equipped with Head Impact Telemetry System (HITS) encoders (Simbex LLC, Lebanon, NH) for the duration of the season, including all practices and games. The University of Rochester Institutional Review Board approved this study, and written informed consent was obtained from all participants.

mTBI cohort. We conducted retrospective analyses on 29 mTBI patients [15 males and 14 females (mean age, 19.5; median age, 19)] and 58 matched controls [44 males and 17 females (mean age, 21.6; median age, 21)]. The individuals diagnosed with concussion are a subset of a broader group of NCAA contact sport athletes at the University of Rochester and the Rochester Institute of Technology who were monitored for concussion. Between 2009 and 2014, 632 NCAA division I and III collegiate contact sport athletes underwent plasma sampling and cognitive testing before the sports season and were followed prospectively for a diagnosis of mTBI. mTBI was defined as an injury witnessed by an on-field certified athletic trainer and meeting the definition of concussion as defined by the Sport Concussion Assessment Tool 2. For the concussed participants in the mTBI cohort, diffusion tensor imaging (DTI) scans and blood samples (for measures of serum-based tau) were collected within 72 hours after injury (and at the same time). We note that the participants enrolled in the mTBI cohort were not wearing accelerometers, and therefore, information about the head hits they sustained is not available for analysis.

Sixteen of the 58 controls took part in various athletic programs at the University of Rochester, but none of those 16 participated in contact sports. That initial group of 16 controls was later supplemented with an additional 42 participants recruited through other studies that matched the critical cohort on age and gender, always using the same DTI acquisition parameters. None of the controls had a history of mTBI.

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