Microstructural Alterations in Tract Development in College Football and Volleyball Players: A Longitudinal Diffusion MRI Study

Abstract

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.

Figure 1. Representative Images of All Diffusion-Based Imaging Metrics Used in the Study

Average maps of first season volleyball players in T1 space through generation of a study-specific atlas (top left). AD = axial Diffusivity; AK = axial kurtosis; AWF = axonal water fraction; FA = fractional anisotropy; FICVF = intracellular volume fraction; FISO = free water (isotropic) volume fraction; MD = mean diffusivity; MK = mean kurtosis; ODI = orientation dispersion index; RD = radial diffusivity; RK = radial kurtosis.

Figure 2. Divergent AWF Trajectory Between Football and Volleyball Players in the Callosum Forceps Minor (Highlighted From Table 2)

(A) Rendering of localized effects. Tractography was performed on a representative volleyball scan. Color coding indicates the node-wise predicted AWF difference between sports using a 3-way interaction model—red indicates larger and blue indicates smaller group differences/effects. (B) Plot of AWF values along the tract nodes (parameterized location 1–10) for football (FB) and volleyball (VB) players for different time points of the study (0 years—red, 2 years—blue, and 4 years—green). (C) The trajectories of AWF values over time across the whole tract, as estimated by the nested linear mixed-effects model, for football (red) and volleyball (blue) players. AWF = axonal water fraction.

Figure 3. Longitudinal Diffusion Metrics in Left Superior Longitudinal Fasciculus (SLF) in Football (FB) vs Volleyball (VB) Players

Left: The trajectories of diffusion metrics values over time across the whole SLF, as estimated by the nested linear mixed-effects model, for football (red) and volleyball (blue) players. Right: The same diffusion metrics for football (FB, left column) and volleyball (VB, right column), plotted along the tract nodes (parameterized location 1–10), for 3 distinct time points over the course of the study (0 years—red, 2 years—blue, and 4 years—green).

Figure 4. Longitudinal Comparison Between (1) Volleyball Players, (2) Football Players With Prior or In-Study Concussion (Concussed), or (3) Without Concussion (Unconcussed)

(A) Summary of tract-specific findings for volleyball vs concussed football players. Upward and downward arrows within each box represent significant longitudinal metric increases and decreases, respectively, in volleyball compared with concussed football players within respective tracts. (B) Heatmaps summarizing tract-specific findings across all comparisons between the 3 groups. Longitudinal changes were more prominent and observed in more tracts when volleyball was compared with concussed football players (left). Heatmap values represent the T-statistic of the “Group x Time” variable from the nested mixed-effect models. Nonsignificant findings are depicted as blank cells. (C) Trajectories of diffusion metric values over time across the left thalamic radiation, as estimated by the nested linear mixed-effects model, for concussed football (red) and volleyball (blue) players.

Figure 5. Acute Effects of Concussion Assessed by Comparing (1) Baseline to Immediately Postconcussion (Concussion) Scans and (2) Concussion to Follow-up Scans

Examples of diffusion metric changes across nodes in baseline, concussion, and follow-up scans: Changes in AD within the left uncinate tract (left) represent a finding exhibiting both effects: baseline vs concussion (T-statistic: 3.9; p value: <0.001) and concussion vs follow-up (T-statistic: −4.2; p value: <0.001) (eTable 2, links.lww.com/WNL/C970). MK differences in the right thalamic radiation (middle) represent changes from baseline to concussion (T-statistic: 4.05; p value: <0.001), while FA differences in the left cingulum cingulate (right) represent changes from concussion to follow-up (T-statistic: 5.69; p value: <0.001). AD = axial diffusivity; FA = fractional anisotropy; MK = mean kurtosis.