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Microstructural Alterations in Tract Development in College Football and Volleyball Players: A Longitudinal Diffusion
Maged Goubran1, Brian David Mills1, Marios Georgiadis1
1From the Departments of Radiology (Maged Goubran, B.D.M., Marios Georgiadis, M.K., N.M., C.A., L.M., D.D., P.S.D., J.R., M.W., M.Z.), Neurosurgery (G.G.), and Bioengineering (D.B.C.), Stanford University, CA; Department of Medical Biophysics (Maged Goubran) and Physical Sciences Platform & Hurvitz Brain Sciences Research Program (Maged Goubran), Sunnybrook Research Institute, University of Toronto, ON, Canada; Stanford Center for Clinical Research (S.S.), CA; Department of Neurology (E.L.D.), University of Utah School of Medicine, Salt Lake City; Department of Radiology (B.B.), Uniformed Services University of the Health Sciences, Bethesda, MD; and Department of Radiology (B.B.), Madigan Army Medical Center, Tacoma, WA.
Background And Objectives:
Repeated impacts in high-contact sports such as 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 with 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, and 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 subconcussive and concussive impacts, and associations between diffusion changes with clinical, behavioral, and sports-related measures.
Results:
Forty-nine football and 24 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 <0.0001). 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 < 0.0001). An analysis of immediate postconcussion scans (n = 12) demonstrated a transient localized increase in axial diffusivity and mean/radial kurtosis in the uncinate and cingulum hippocampus (|T| > 3.7, p < 0.0001). Finally, within football players, those with high position-based impact risk demonstrated increased intracellular volume fraction longitudinally (T = 3.6, p < 0.0001).
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, nondecreasing axonal dispersion. This prospective longitudinal study demonstrates divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and repeated subconcussive impact-related alteration of white matter development in football athletes.
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