Background and Objectives: Repeated concussive and sub-concussive impacts in high-contact sports can affect microstructure of the brain, which can be studied using diffusion MRI. Most prior imaging studies, however, employ a cross-sectional design, do not include low-contact players as controls, or use traditional diffusion tensor imaging without investigating novel tract-specific microstructural metrics. Methods: We examined brain microstructure in 63 high-contact (American football) and 34 low-contact (volleyball) collegiate athletes with up to 4 years of follow-up (315 total scans) using advanced diffusion MRI, a comprehensive set of multi-compartment models, and automated fiber quantification tools. We investigated diffusion metrics along the length of tracts using nested linear mixed-effects models to ascertain the acute and chronic effects of sub-concussive and concussive impacts, as well as associations between diffusion changes with clinical, behavioral, and sports-related measures. Results: Significant longitudinal increases in fractional anisotropy and axonal water fraction were detected in volleyball players, but not in football players, along with decreases in radial and mean diffusivity as well as orientation dispersion index (all findings absolute T-statistic > 3.5, p < .0001). This pattern was present in the callosum forceps minor, left superior longitudinal fasciculus, left thalamic radiation, and right cingulum hippocampus. Longitudinal group differences were more prominent and observed in a larger number of tracts in concussed (previously or in-study) football players (p < .0001), while smaller effects were noted in un-concussed players. An analysis of immediate-post concussion scans in football players demonstrated a transient localized increase in axial diffusivity, mean and radial kurtosis in the left uncinate and right cingulum hippocampus (p < .0001). Finally, football players with high position-based sub-concussive risk demonstrated increased orientation dispersion index over time (p < .0001). Discussion: The observed longitudinal changes in our volleyball cohort likely reflect normal development in this age range, while the relative attenuation of these effects seen in football, and especially concussed athletes, could possibly reveal diminished myelination, altered axonal calibers, or depressed pruning processes leading to a static, non-decreasing axonal dispersion. This prospective longitudinal study demonstrates significantly divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and/or repeated sub-concussive impact-related alteration of normal white matter development in football athletes.

Background and Objectives:Repeated impacts in high-contact sports like American football can affect the brain’s microstructure, which can be studied using diffusion MRI. Most imaging studies are cross-sectional, do not include low-contact players as controls, or lack advanced tract-specific microstructural metrics. We aimed to investigate longitudinal changes in high-contact collegiate athletes compared to low-contact controls using advanced diffusion MRI and automated fiber quantification.Methods:We examined brain microstructure in high-contact (football) and low-contact (volleyball) collegiate athletes with up to 4 years of follow-up. Inclusion criteria included university and team enrollment. Exclusion criteria included history of neurosurgery, severe brain injury, major neurologic or substance abuse disorder. We investigated diffusion metrics along the length of tracts using nested linear mixed-effects models to ascertain the acute and chronic effects of sub-concussive and concussive impacts, and associations between diffusion changes with clinical, behavioral, and sports-related measures.Results:Forty-nine football and twenty-four volleyball players (271 total scans) were included. Football players had significantly divergent trajectories in multiple microstructural metrics and tracts. Longitudinal increases in fractional anisotropy and axonal water fraction, and decreases in radial/mean diffusivity and orientation dispersion index, were present in volleyball but absent in football players (all findings |T-statistic|> 3.5, p-value < .0001). This pattern was present in the callosum forceps minor, superior longitudinal fasciculus, thalamic radiation, and cingulum hippocampus. Longitudinal differences were more prominent and observed in more tracts in concussed football players (n=24, |T|> 3.6, p < .0001). An analysis of immediate-post concussion scans (n=12) demonstrated a transient localized increase in axial diffusivity, mean/radial kurtosis in the uncinate and cingulum hippocampus (|T| > 3.7, p < .0001). Finally, within football players, those with high position-based impact risk demonstrated increased intra-cellular volume fraction longitudinally (T = 3.6, p < .0001).Discussion:The observed longitudinal changes seen in football, and especially concussed athletes, could reveal diminished myelination, altered axonal calibers, or depressed pruning processes leading to a static, non-decreasing axonal dispersion. This prospective longitudinal study demonstrates divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and repeated sub-concussive impact-related alteration of white matter development in football athletes.

ObjectiveRepetitive head trauma is common in high‐contact sports. Cerebral blood flow (CBF) can measure changes in brain perfusion that could indicate injury. Longitudinal studies with a control group are necessary to account for interindividual and developmental effects. We investigated whether exposure to head impacts causes longitudinal CBF changes.MethodsWe prospectively studied 63 American football (high‐contact cohort) and 34 volleyball (low‐contact controls) male collegiate athletes, tracking CBF using 3D pseudocontinuous arterial spin labeling magnetic resonance imaging for up to 4 years. Regional relative CBF (rCBF, normalized to cerebellar CBF) was computed after co‐registering to T1‐weighted images. A linear mixed effects model assessed the relationship of rCBF to sport, time, and their interaction. Within football players, we modeled rCBF against position‐based head impact risk and baseline Standardized Concussion Assessment Tool score. Additionally, we evaluated early (1–5 days) and delayed (3–6 months) post‐concussion rCBF changes (in‐study concussion).ResultsSupratentorial gray matter rCBF declined in football compared with volleyball (sport‐time interaction p = 0.012), with a strong effect in the parietal lobe (p = 0.002). Football players with higher position‐based impact‐risk had lower occipital rCBF over time (interaction p = 0.005), whereas players with lower baseline Standardized Concussion Assessment Tool score (worse performance) had relatively decreased rCBF in the cingulate‐insula over time (interaction effect p = 0.007). Both cohorts showed a left–right rCBF asymmetry that decreased over time. Football players with an in‐study concussion showed an early increase in occipital lobe rCBF (p = 0.0166).InterpretationThese results suggest head impacts may result in an early increase in rCBF, but cumulatively a long‐term decrease in rCBF. ANN NEUROL 2023

Longitudinal changes (over four years) of cerebral blood flow (CBF) using arterial spin labeling MRI were investigated in a population of high-contact sport football college athletes and were compared to low-contact cohort of volleyball athletes. A linear-mixed-effects model was applied to assess CBF (normalized to the cerebellum) by sport (football vs. volleyball), time from baseline MRI, and the interaction between sport and time. Longitudinal analysis showed a prospective decline in perfusion in football compared to volleyball. Fourteen football players experienced an in-study concussion; in contrast to the longitudinal findings, football players exhibited acutely a mild increase in occipital lobe CBF.

BACKGROUND There is need for non-pharmaceutical treatments for COVID-19. A home-use photobiomodulation (PBM) device was tested as Treatment in a randomized clinical trial. METHODS 294 patients were randomized with equal allocation to Treatment or Standard of Care (Control). 199 qualified for efficacy analyses. The Treatment group self-treated for 20 minutes twice daily, for the first 5 days, and subsequently once daily for 30 days. A validated respiratory questionnaire was used, and patients were monitored remotely. The primary endpoint was the time-to-recovery (3 consecutive days of no sickness) for general sickness. The Kaplan-Meier method and the Cox Proportional Hazards model were primary methods of analyses. RESULTS Treatment patients with collective 0-12 days of symptoms, at moderate-to-severe level on Day 1 of Treatment, did not recover significantly faster than Control. However, for patients with 0-7 days of symptoms there was a significant mean difference of 3 days: Treatment, 18 days (95% CI, 13-20) vs. Control, 21 days (95% CI, 15-28), P=0.050. The Treatment:Control hazard ratio at 1.495 (95% CI, 0.996-2.243), P=0.054 exceeded the pre-trial target of 1.44. Treated patients exceeding 7 days symptoms duration were more tired and had lower energy. None of the patients in the Treatment group suffered death or hospitalization while the Control group had 1 death and 3 severe adverse events requiring hospitalization. CONCLUSIONS Patients with up to 7 days of symptoms at moderate-to-severe levels on first day of Treatment can expect faster recovery for general sickness and several respiratory symptoms. (Funded by Vielight Inc.; ClinicalTrials.gov number, NCT04418505.)