Investigating Brain White Matter in Football Players with and without Concussion Using a Biophysical Model from Multishell Diffusion MRI

Abstract

Background and purpose: There have been growing concerns around potential risks related to sports-related concussion and contact sport exposure to repetitive head impacts in young athletes. Here we investigate WM microstructural differences between collegiate football players with and without sports-related concussion.

Materials and methods: The study included 78 collegiate athletes (24 football players with sports-related concussion, 26 football players with repetitive head impacts, and 28 non-contact-sport control athletes), available through the Federal Interagency Traumatic Brain Injury Research registry. Diffusion metrics of diffusion tensor/kurtosis imaging and WM tract integrity were calculated. Tract-Based Spatial Statistics and post hoc ROI analyses were performed to test group differences.

Results: Significantly increased axial kurtosis in those with sports-related concussion compared with controls was observed diffusely across the whole-brain WM, and some focal areas demonstrated significantly higher mean kurtosis and extra-axonal axial diffusivity in sports-related concussion. The extent of significantly different WM regions decreased across time points and remained present primarily in the corpus callosum. Similar differences in axial kurtosis were found between the repetitive head impact and control groups. Other significant differences were seen at unrestricted return-to-play with lower radial kurtosis and intra-axonal diffusivity in those with sports-related concussion compared with the controls, mainly restricted to the posterior callosum.

Conclusions: This study highlights the fact that there are differences in diffusion microstructure measures that are present not only between football players with sports-related injuries and controls, but that there are also measurable differences between football players with repetitive head impacts and controls. This work reinforces previous work showing that the corpus callosum is specifically implicated in sports-related concussion and also suggests this to be true for repetitive head impacts.

FIG 1.

TBSS results comparing SRC and HC groups at time point 1 (24–48 hours postinjury for SRC; baseline for HC). Top, significant voxels (blue) demonstrating increased AK in the SRC group are present diffusely throughout the WM. Increased MK (middle) and D_e,‖ (bottom) in the SRC group are also seen in more focal areas of middle posterior WM regions including the external capsule, posterior limb of the internal capsule, cerebral peduncle, uncinate fasciculus, inferior longitudinal fasciculus, posterior thalamic radiation, retrolenticular part of internal capsule, and splenium of the corpus callosum. The significance level was P < .05, corrected for multiple comparisons by controlling the family-wise error rate. Significant voxels were enlarged using TBSS fill (FSL command; https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/TBSS/UserGuide#Displaying_TBSS_Results) for illustrative purposes and were overlapped onto the mean FA skeleton (green).

FIG 2.

Evolution of differences in AK between the SRC and HC groups across 4 time points. A, Maps show regions along the WM skeleton that demonstrate a significant difference (blue) in AK between the SRC and HC groups across 4 time points (T1–T4). B, Corresponding bar graphs show the percentage of significantly different voxels on the skeleton across time points. The extent of significantly different WM regions decreases across time points, remaining present primarily within the corpus callosum at time point 4.

FIG 3.

TBSS results comparing the RHI and HC groups (time point 1): Clusters of voxels (blue) demonstrating significantly higher AK and MK in the RHI group compared with the HC group are also present diffusely across the entire WM. Additionally, increased D_e,‖ and AWF in the RHI group are seen in focal areas of WM regions including the corpus callosum, corona radiata, superior longitudinal fasciculus, posterior limb of the internal capsule, retrolenticular part of the internal capsule, posterior thalamic radiation, and cerebral peduncle. The significance level was P < .05, corrected for multiple comparisons by controlling the family-wise error rate.