A Review of Head Injury Metrics Used in Automotive Safety and Sports Protective Equipment.

Despite advances in the understanding of human tolerances to brain injury, injury metrics used in automotive safety and protective equipment standards have changed little since they were first implemented nearly a half-century ago. Although numerous metrics have been proposed as improvements over the ones currently used, evaluating the predictive capability of these metrics is challenging. The purpose of this review is to summarize existing head injury metrics that have been proposed for both severe head injuries, such as skull fractures and traumatic brain injuries (TBI), and mild traumatic brain injuries (mTBI) including concussions. Metrics have been developed based on head kinematics or intracranial parameters such as brain tissue stress and strain. Kinematic metrics are either based on translational motion, rotational motion, or a combination of the two. Tissue-based metrics are based on finite element model simulations or in vitro experiments. This review concludes with a discussion of the limitations of current metrics and how improvements can be made in the future.

Neuropsychological Change After a Single Season of Head Impact Exposure in Youth Football.

OBJECTIVES: Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes. METHOD: Over 200 participants (ages 9-13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season. Pre- and post-season neuropsychological tests were completed. Test score changes were calculated adjusting for practice effects and regression to the mean and used as the dependent variables. Regression models were calculated with HIE variables predicting neuropsychological test score changes. RESULTS: For the full sample, a small effect was found with season average rotational values predicting changes in list-learning such that HIE was related to negative score change: standardized beta (ß) = -.147, t(205) = -2.12, and p = .035. When analyzed by age clusters (9-10, 11-13) and adding participant weight to models, the R2 values increased. Splitting groups by weight (median split), found heavier members of the 9-10 cohort with significantly greater change than lighter members. Additionaly, significantly more participants had clinically meaningful negative changes: X2 = 10.343, p = .001. CONCLUSION: These findings suggest that in the 9-10 age cluster, the average seasonal level of HIE had inverse, negative relationships with cognitive change over one season that was not found in the older group. The mediation effects of age and weight have not been explored previously and appear to contribute to the effects of HIE on cognition in youth football players.

Laboratory Evaluation of Low-Cost Wearable Sensors for Measuring Head Impacts in Sports.

Advances in low-cost wearable head impact sensor technology provide potential benefits regarding sports safety for both consumers and researchers. However, previous laboratory evaluations are not directly comparable and do not incorporate test conditions representative of unhelmeted impacts. This study addresses those limitations. The xPatch by X2 Biosystems and the SIM-G by Triax Technologies were placed on a National Operating Committee on Standards for Athletic Equipment (NOCSAE) headform with a Hybrid III neck which underwent impact tests using a pendulum. Impact conditions included helmeted, padded impactor to bare head, and rigid impactor to bare head to represent long- and short-duration impacts seen in helmeted and unhelmeted sports. The wearable sensors were evaluated on their kinematic accuracy by comparing results to reference sensors located at the headform center of gravity. Statistical tests for equivalence were performed on the slope of the linear regression between wearable sensors and reference. The xPatch gave equivalent measurements to the reference in select longer-duration impacts, whereas the SIM-G had large variance leading to no equivalence. For the short-duration impacts, both wearable sensors underpredicted the reference. This error can be improved with increases in sampling rate from 1 to 1.5 kHz. Follow-up evaluations should be performed on the field to identify error in vivo.

Head Impact Exposure in Practices Correlates With Exposure in Games for Youth Football Players.

This study aimed to compare head impact exposures between practices and games in football players ages 9 to 14 years, who account for approximately 70% of all football players in the United States. Over a period of 2 seasons, 136 players were enrolled from 3 youth programs, and 49,847 head impacts were recorded from 345 practices and 137 games. During the study, individual players sustained a median of 211 impacts per season, with a maximum of 1226 impacts. Players sustained 50th (95th) percentile peak linear acceleration of 18.3 (46.9) g, peak rotational acceleration of 1305.4 (3316.6) rad·s-2, and Head Impact Technology Severity Profile of 13.7 (24.3), respectively. Overall, players with a higher frequency of head impacts at practices recorded a higher frequency of head impacts at games (P < .001, r2 = .52), and players who sustained a greater average magnitude of head impacts during practice also recorded a greater average magnitude of head impacts during games (P < .001). The youth football head impact data quantified in this study provide valuable insight into the player exposure profile, which should serve as a key baseline in efforts to reduce injury.

Head impact exposure in youth football: middle school ages 12-14 years.

The head impact exposure experienced by football players at the college and high school levels has been well documented; however, there are limited data regarding youth football despite its dramatically larger population. The objective of this study was to investigate head impact exposure in middle school football. Impacts were monitored using a commercially available accelerometer array installed inside the helmets of 17 players aged 12-14 years. A total of 4678 impacts were measured, with an average (±standard deviation) of 275 ± 190 impacts per player. The average of impact distributions for each player had a median impact of 22 ± 2 g and 954 ± 122 rad/s², and a 95th percentile impact of 54 ± 9 g and 2525 ± 450 rad/s². Similar to the head impact exposure experienced by high school and collegiate players, these data show that middle school football players experience a greater number of head impacts during games than practices. There were no significant differences between median and 95th percentile head acceleration magnitudes experienced during games and practices; however, a larger number of impacts greater than 80 g occurred during games than during practices. Impacts to the front and back of the helmet were most common. Overall, these data are similar to high school and college data that have been collected using similar methods. These data have applications toward youth football helmet design, the development of strategies designed to limit head impact exposure, and child-specific brain injury criteria.

Head impact exposure in youth football: elementary school ages 7-8 years and the effect of returning players.

OBJECTIVE: To provide data describing the head impact exposure of 7- to 8-year-old football players. DESIGN: Head impact data were collected from 19 players over the course of 2 seasons using helmet-mounted accelerometer arrays. SETTING: Data were collected from 2 youth football teams in Blacksburg, VA, spanning 2 seasons. PARTICIPANTS: A total of 19 youth football players aged 7-8 years. INDEPENDENT VARIABLES: Type of session (practice or game) and the player's experience. MAIN OUTCOME MEASURES: Head impact frequency, acceleration magnitude, and impact location for games, practices, and the season as a whole were measured. RESULTS: The average instrumented player sustained 9 ± 6 impacts per practice, 11 ± 11 impacts per game, and 161 ± 111 impacts per season. The average instrumented player had a median impact of 16 ± 2 g and 686 ± 169 rad/s and a 95th percentile impact of 38 ± 13 g and 2052 ± 664 rad/s throughout a season. Impacts of 40 g or greater tended to occur more frequently in practices than in games, and practices had a significantly higher 95th percentile impact magnitude than games (P = 0.023). Returning players had significantly more impacts than first time players (P = 0.007). CONCLUSIONS: These data are a further step toward developing effective strategies to reduce the incidence of concussion in youth football and have applications toward youth-specific football helmet designs.

Association of Premorbid Anxiety and Depression Symptoms in Concussion Recovery in Collegiate Student-Athletes.

BACKGROUND: Mental health disorders are linked to prolonged concussion symptoms. However, the association of premorbid anxiety/depression symptoms with postconcussion return-to-play timelines and total symptom burden is unclear. OBJECTIVE: To examine the association of self-reported premorbid anxiety/depression symptoms in collegiate student-athletes with (1) recovery times until asymptomatic, (2) return-to-play, and (3) postconcussion symptom burden. STUDY DESIGN: Athletes in the Concussion Assessment, Research and Education Consortium completed baseline concussion assessments (Sport Concussion Assessment Tool [SCAT3] and Brief Symptom Inventory-18 [BSI-18]). Athletes were tested postinjury at <6 hours, 24 to 48 hours, time of asymptomatic and start of return-to-play protocol, unrestricted return-to-play, and 6 months after injury. Injured athletes were categorized into 4 groups based on BSI-18 scores: (1) B-ANX, elevated anxiety symptoms only; (2) B-DEP, elevated depression symptoms only; (3) B-ANX&DEP, elevated anxiety and depression symptoms; and (4) B-NEITHER, no elevated anxiety or depression symptoms. Relationship between age, sex, BSI-18 group, SCAT3 total symptom and severity scores, and time to asymptomatic status and return-to-play was assessed with Pearson's chi-squared test and robust analysis of variance. LEVEL OF EVIDENCE: Level 3. RESULTS: Among 1329 athletes with 1352 concussions, no respondents had a self-reported premorbid diagnosis of anxiety/depression. There was no difference in time until asymptomatic or time until return-to-play between BSI-18 groups (P = 0.15 and P = 0.11, respectively). B-ANX, B-DEP, and B-ANX&DEP groups did not have higher total symptom or severity scores postinjury compared with the B-NEITHER group. CONCLUSION: Baseline anxiety/depression symptoms in collegiate student-athletes without a mental health diagnosis are not associated with longer recovery times until asymptomatic, longer time to return-to-play, or higher postconcussion total symptom and severity scores compared with athletes without baseline symptoms. CLINICAL RELEVANCE: Anxiety and depression symptoms without a clear mental health diagnosis should be considered differently from other comorbidities when discussing prolonged recovery in collegiate student-athletes.

The Prevalence and Influence of New or Worsened Neck Pain After a Sport-Related Concussion in Collegiate Athletes: A Study From the CARE Consortium.

BACKGROUND: Neck pain in a concussion population is an emerging area of study that has been shown to have a negative influence on recovery. This effect has not yet been studied in collegiate athletes. HYPOTHESIS: New or worsened neck pain is common after a concussion (>30%), negatively influences recovery, and is associated with patient sex and level of contact in sport. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Varsity-level athletes from 29 National Collegiate Athletic Association member institutions as well as nonvarsity sport athletes at military service academies were eligible for enrollment. Participants completed a preseason baseline assessment and follow-up assessments at 6 and 24 to 48 hours after a concussion, when they were symptom-free, and when they returned to unrestricted play. Data collection occurred between January 2014 and September 2018. RESULTS: A total of 2163 injuries were studied. New or worsened neck pain was reported with 47.0% of injuries. New or worsened neck pain was associated with patient sex (higher in female athletes), an altered mental status after the injury, the mechanism of injury, and what the athlete collided with. The presence of new/worsened neck pain was associated with delayed recovery. Those with new or worsened neck pain had 11.1 days of symptoms versus 8.8 days in those without (P < .001). They were also less likely to have a resolution of self-reported symptoms in ≤7 days (P < .001). However, the mean duration of the return-to-play protocol was not significantly different for those with new or worsened neck pain (7.5 ± 7.7 days) than those without (7.4 ± 8.3 days) (P = .592). CONCLUSION: This novel study shows that neck pain was common in collegiate athletes sustaining a concussion, was influenced by many factors, and negatively affected recovery.

Effect of strain rate on the material properties of human liver parenchyma in unconfined compression.

The liver is one of the most frequently injured organs in abdominal trauma. Although motor vehicle collisions are the most common cause of liver injuries, current anthropomorphic test devices are not equipped to predict the risk of sustaining abdominal organ injuries. Consequently, researchers rely on finite element models to assess the potential risk of injury to abdominal organs such as the liver. These models must be validated based on appropriate biomechanical data in order to accurately assess injury risk. This study presents a total of 36 uniaxial unconfined compression tests performed on fresh human liver parenchyma within 48 h of death. Each specimen was tested once to failure at one of four loading rates (0.012, 0.106, 1.036, and 10.708 s-1) in order to investigate the effects of loading rate on the compressive failure properties of human liver parenchyma. The results of this study showed that the response of human liver parenchyma is both nonlinear and rate dependent. Specifically, failure stress significantly increased with increased loading rate, while failure strain significantly decreased with increased loading rate. The failure stress and failure strain for all liver parenchyma specimens ranged from -38.9 kPa to -145.9 kPa and from -0.48 strain to -1.15 strain, respectively. Overall, this study provides novel biomechanical data that can be used in the development of rate dependent material models and the identification of tissue-level tolerance values, which are critical to the validation of finite element models used to assess injury risk.

Are EPB41 and alpha-synuclein diagnostic biomarkers of sport-related concussion? Findings from the NCAA and Department of Defense CARE Consortium.

BACKGROUND: Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion. Therefore, more accurate diagnostic markers are needed for sport-related concussion. METHODS: This was a multicenter, prospective, case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research, and Education Consortium conducted between 2015 and 2019. The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints. Athletes with concussion were divided into 6 h post-injury (0-6 h post-injury) and after 6 h post-injury (7-48 h post-injury) groups. We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305 proteins in plasma samples from athletes with and without sport-related concussion. RESULTS: A total of 140 athletes with concussion (79.3% males; aged 18.71 ± 1.10 years, mean ± SD) and 21 non-concussed athletes (76.2% males; 19.14 ± 1.10 years) were included in this study. We identified 338 plasma proteins that significantly differed in abundance (319 upregulated and 19 downregulated) in concussed athletes compared to non-concussed athletes. The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve (AUC) of 0.954 (95% confidence interval: 0.922‒0.986). Specifically, after 6 h of injury, the individual AUC of plasma erythrocyte membrane protein band 4.1 (EPB41) and alpha-synuclein (SNCA) were 0.956 and 0.875, respectively. The combination of EPB41 and SNCA provided the best AUC (1.000), which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury. CONCLUSION: Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.

Longitudinal Associations Between Blood Biomarkers and White Matter MRI in Sport-Related Concussion: A Study of the NCAA-DoD CARE Consortium.

BACKGROUND AND OBJECTIVES: To study longitudinal associations between blood-based neural biomarkers (including total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP], and ubiquitin C-terminal hydrolase-L1) and white matter neuroimaging biomarkers in collegiate athletes with sport-related concussion (SRC) from 24 hours postinjury to 1 week after return to play. METHODS: We analyzed clinical and imaging data of concussed collegiate athletes in the Concussion Assessment, Research, and Education (CARE) Consortium. The CARE participants completed same-day clinical assessments, blood draws, and diffusion tensor imaging (DTI) at 3 time points: 24-48 hours postinjury, point of becoming asymptomatic, and 7 days after return to play. DTI probabilistic tractography was performed for each participant at each time point to render 27 participant-specific major white matter tracts. The microstructural organization of these tracts was characterized by 4 DTI metrics. Mixed-effects models with random intercepts were applied to test whether white matter microstructural abnormalities are associated with the blood-based biomarkers at the same time point. An interaction model was used to test whether the association varies across time points. A lagged model was used to test whether early blood-based biomarkers predict later microstructural changes. RESULTS: Data from 77 collegiate athletes were included in the following analyses. Among the 4 blood-based biomarkers, total tau had significant associations with the DTI metrics across the 3 time points. In particular, high tau level was associated with high radial diffusivity (RD) in the right corticospinal tract (ß = 0.25, SE = 0.07, p FDR-adjusted = 0.016) and superior thalamic radiation (ß = 0.21, SE = 0.07, p FDR-adjusted = 0.042). NfL and GFAP had time-dependent associations with the DTI metrics. NfL showed significant associations only at the asymptomatic time point (|ß|s > 0.12, SEs <0.09, psFDR-adjusted < 0.05) and GFAP showed a significant association only at 7 days after return to play (ßs > 0.14, SEs <0.06, psFDR-adjusted < 0.05). The p values for the associations of early tau and later RD were not significant after multiple comparison adjustment, but were less than 0.1 in 7 white matter tracts. DISCUSSION: This prospective study using data from the CARE Consortium demonstrated that in the early phase of SRC, white matter microstructural integrity detected by DTI neuroimaging was associated with elevated levels of blood-based biomarkers of traumatic brain injury. Total tau in the blood showed the strongest association with white matter microstructural changes.

Gene Expression Alterations in Peripheral Blood Following Sport-Related Concussion in a Prospective Cohort of Collegiate Athletes: A Concussion Assessment, Research and Education (CARE) Consortium Study.

BACKGROUND: Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury. OBJECTIVE: The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery. METHODS: We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline. RESULTS: Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion. CONCLUSIONS: Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.

Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts.

Objective: The aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes. Methods: This pilot study comprised two independent cohorts. The first cohort-part of a Traumatic Head Injury Neuroimaging Classification (THINC) study-with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort-with a mean age of 19 years-comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay. Results: Concentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690-0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT-/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT-/MRI-, n = 111) findings and UIC (P-values < 0.05). Conclusion: These findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions.

Magnitude of head impact exposures in individual collegiate football players.

The purpose of this study was to quantify the severity of head impacts sustained by individual collegiate football players and to investigate differences between impacts sustained during practice and game sessions, as well as by player position and impact location. Head impacts (N = 184,358) were analyzed for 254 collegiate players at three collegiate institutions. In practice, the 50th and 95th percentile values for individual players were 20.0 g and 49.5 g for peak linear acceleration, 1187 rad/s2 and 3147 rad/s2 for peak rotational acceleration, and 13.4 and 29.9 for HITsp, respectively. Only the 95th percentile HITsp increased significantly in games compared with practices (8.4%, p = .0002). Player position and impact location were the largest factors associated with differences in head impacts. Running backs consistently sustained the greatest impact magnitudes. Peak linear accelerations were greatest for impacts to the top of the helmet, whereas rotational accelerations were greatest for impacts to the front and back. The findings of this study provide essential data for future investigations that aim to establish the correlations between head impact exposure, acute brain injury, and long-term cognitive deficits.

Whitewater Helmet STAR: Evaluation of the Biomechanical Performance and Risk of Head Injury for Whitewater Helmets.

More than six million people participate in whitewater kayaking and rafting in the United States each year. Unfortunately, with these six million whitewater participants come 50 deaths annually, making it one of the highest fatality rates of all sports. As the popularity in whitewater activities grows, the number of injuries, including concussions, also increases. The objective of this study was to create a new rating system for whitewater helmets by evaluating the biomechanical performance and risk of head injury of whitewater helmets using the Summation of Tests for the Analysis of Risk (STAR) system. All watersport helmets that passed the EN: 1385: 2012 standard and that were clearly marketed for whitewater use were selected for this study. Two samples of each helmet model were tested on a custom pendulum impactor under conditions known to be associated with the highest risk of head injury and death. A 50th percentile male NOCSAE headform instrumented with three linear accelerometers and a triaxial angular rate sensor coupled with a Hybrid III 50th percentile neck were used for data collection. A total of 126 tests were performed using six different configurations. These included impacts to the front, side, and rear using two speeds of 3.1 and 4.9 m/s that modeled whitewater river flow rates. Each helmet's STAR score was calculated using the combination of exposure and injury risk that was determined from the linear and rotational head accelerations. The resulting head impact accelerations predicted a very high risk of concussion for all impact locations at the 4.9 m/s speed. The STAR score varied between helmets indicating that some helmets provide better protection than others. Overall, these results show a clear need for improvement in whitewater helmets, and the methodologies developed in this research project should provide manufacturers a design tool for improving these products.

Association between Preseason/Regular Season Head Impact Exposure and Concussion Incidence in NCAA Football.

PURPOSE: Contact sport athletes are exposed to a unique environment where they sustain repeated head impacts throughout the season and can sustain hundreds of head impacts over a few months. Accordingly, recent studies outlined the role that head impact exposure (HIE) has in concussion biomechanics and in the development of cognitive and brain-based changes. Those studies focused on time-bound effects by quantifying exposure leading up to the concussion, or cognitive changes after a season in which athletes had high HIE. However, HIE may have a more prolonged effect. This study identified associations between HIE and concussion incidence during different periods of the college football fall season. METHODS: This study included 1120 athlete seasons from six National Collegiate Athletic Association Division I football programs across 5 yr. Athletes were instrumented with the Head Impact Telemetry System to record daily HIE. The analysis quantified associations of preseason/regular season/total season concussion incidence with HIE during those periods. RESULTS: Strong associations were identified between HIE and concussion incidence during different periods of the season. Preseason HIE was associated with preseason and total season concussion incidence, and total season HIE was associated with total season concussion incidence. CONCLUSIONS: These findings demonstrate a prolonged effect of HIE on concussion risk, wherein elevated preseason HIE was associated with higher concussion risk both during the preseason and throughout the entire fall season. This investigation is the first to provide evidence supporting the hypothesis of a relationship between elevated HIE during the college football preseason and a sustained decreased tolerance for concussion throughout that season.

Head Impact Exposure in Youth and Collegiate American Football.

The relationship between head impact and subsequent brain injury for American football players is not well-defined, especially for youth. The objective of this study is to quantify and assess Head Impact Exposure (HIE) metrics among youth and collegiate football players. This multi-season study enrolled 639 unique athletes (354 collegiate; 285 youth, ages 9-14), recording 476,209 head impacts (367,337 collegiate; 108,872 youth) over 971 sessions (480 collegiate; 491 youth). Youth players experienced 43 and 65% fewer impacts per competition and practice, respectively, and lower impact magnitudes compared to collegiate players (95th percentile peak linear acceleration (PLA, g) competition: 45.6 vs 61.9; 95th percentile PLA practice: 42.6 vs 58.8; 95th percentile peak rotational acceleration (PRA, rad·s-2) competition: 2262 vs 4422; 95th percentile PRA practice: 2081 vs 4052; 95th percentile HITsp competition: 25.4 vs 32.8; 95th percentile HITsp practice: 23.9 vs 30.2). Impacts during competition were more frequent and of greater magnitude than during practice at both levels. Quantified comparisons of head impact frequency and magnitude between youth and collegiate athletes reveal HIE differences as a function of age, and expanded insight better informs the development of age-appropriate guidelines for helmet design, prevention measures, standardized testing, brain injury diagnosis, and recovery management.

Effects of White-Matter Tract Length in Sport-Related Concussion: A Tractography Study from the NCAA-DoD CARE Consortium.

Sport-related concussion (SRC) is an important public health issue. White-matter alterations after SRC are widely studied by neuroimaging approaches, such as diffusion magnetic resonance imaging (MRI). Although the exact anatomical location of the alterations may differ, significant white-matter alterations are commonly observed in long fiber tracts, but are never proven. In the present study, we performed streamline tractography to characterize the association between tract length and white-matter microstructural alterations after SRC. Sixty-eight collegiate athletes diagnosed with acute concussion (24-48 h post-injury) and 64 matched contact-sport controls were included in this study. The athletes underwent diffusion tensor imaging (DTI) in 3.0 T MRI scanners across three study sites. DTI metrics were used for tract-based spatial statistics to map white-matter regions-of-interest (ROIs) with significant group differences. Whole-brain white-mater streamline tractography was performed to extract "affected" white-matter streamlines (i.e., streamlines passing through the identified ROIs). In the concussed athletes, streamline counts and DTI metrics of the affected white-matter fiber tracts were summarized and compared with unaffected white-matter tracts across tract length in the same participant. The affected white-matter tracts had a high streamline count at length of 80-100 mm and high length-adjusted affected ratio for streamline length longer than 80 mm. DTI mean diffusivity was higher in the affected streamlines longer than 100 mm with significant associations with the Brief Symptom Inventory score. Our findings suggest that long fibers in the brains of collegiate athletes are more vulnerable to acute SRC with higher mean diffusivity and a higher affected ratio compared with the whole distribution.

Proteomic Profiling of Plasma Biomarkers Associated With Return to Sport Following Concussion: Findings From the NCAA and Department of Defense CARE Consortium.

Objective: To investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC). Methods: This multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes (n = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery <14-days (n = 99) and (2) recovery ≥14-days (n = 41). We applied a highly multiplexed proteomic technique that uses DNA aptamers assay to target 1,305 proteins in plasma samples from concussed athletes with <14-days and ≥14-days. Results: We identified 87 plasma proteins significantly dysregulated (32 upregulated and 55 downregulated) in concussed athletes with recovery ≥14-days relative to recovery <14-days groups. The significantly dysregulated proteins were uploaded to Ingenuity Pathway Analysis (IPA) software for analysis. Pathway analysis showed that significantly dysregulated proteins were associated with STAT3 pathway, regulation of the epithelial mesenchymal transition by growth factors pathway, and acute phase response signaling. Conclusion: Our data showed the feasibility of large-scale plasma proteomic profiling in concussed athletes with a <14-days and ≥ 14-days recovery. These findings provide a possible understanding of the pathophysiological mechanism in neurobiological recovery. Further study is required to determine whether these proteins can aid clinicians in RTS decisions.

Time Delta Head Impact Frequency: An Analysis on Head Impact Exposure in the Lead Up to a Concussion: Findings from the NCAA-DOD Care Consortium.

Sport-related concussions can result from a single high magnitude impact that generates concussive symptoms, repeated subconcussive head impacts aggregating to generate concussive symptoms, or a combined effect from the two mechanisms. The array of symptoms produced by these mechanisms may be clinically interpreted as a sport-related concussion. It was hypothesized that head impact exposure resulting in concussion is influenced by severity, total number, and frequency of subconcussive head impacts. The influence of total number and magnitude of impacts was previously explored, but frequency was investigated to a lesser degree. In this analysis, head impact frequency was investigated over a new metric called 'time delta', the time difference from the first recorded head impact of the day until the concussive impact. Four exposure metrics were analyzed over the time delta to determine whether frequency of head impact exposure was greater for athletes on their concussion date relative to other dates of contact participation. Those metrics included head impact frequency, head impact accrual rate, risk weighted exposure (RWE), and RWE accrual rate. Athletes experienced an elevated median number of impacts, RWE, and RWE accrual rate over the time delta on their concussion date compared to non-injury sessions. This finding suggests elevated frequency of head impact exposure on the concussion date compared to other dates that may precipitate the onset of concussion.