INTRODUCTION

Repetitive head impacts (RHI) are associated with cognitive decline¹, and changes within the deep white matter microstructure². Finite element modelling of RHI found that the depths of the cortical sulci received a high-strain rate deformation response³. Postmortem evidence of hyperphosphorylated tau deposition localized to the cortical sulci are hallmarks of Chronic Traumatic Encephalopathy (CTE)⁴ and have been associated with a history of RHI⁴. CTE pathology within the sulcal fundi has been observed post-mortem in young athletes exposed to repetitive head impacts⁵. A highly significant relationship of sulcal FA from DTI with pathologic evidence of axon disruption was demonstrated with ex vivo post-mortem MRI in American Football players⁶. Here we report the first in vivo magnetic resonance imaging evidence of RHI-related white matter microstructure changes at the sulcal fundi and gyral crowns of adult amateur soccer players.

METHODS

Healthy amateur adult soccer players and healthy non-collision athlete controls with no history of RHI were included in this analysis. Study procedures have been reported in detail^2,7-10. In brief, amateur soccer players were recruited from the New York City metropolitan area. A validated, structured, computer-administered questionnaire (HeadCount¹¹) was used to estimate soccer heading exposure over the prior year. Imaging was performed using a 3.0T Philips Achieva TX scanner and a 32-channel head coil. T1-weighted 3D magnetization-prepared rapid acquisition of gradient echo imaging was performed with TR/TE/TI = 9.9/4.6/900 ms, flip angle 8°, 1 mm³ isotropic resolution, 240 × 188 × 220 matrix. DTI was performed using 2D single-shot EPI with 32 diffusion encoding directions, b-value = 800 s/mm², TR = 10 s, TE = 65 ms, 2 mm³ isotropic resolution, 128 × 120 matrix, 70 slices. Automated image analysis algorithms¹² were used to extract fractional anisotropy (FA), separately for each player’s sulcal fundi and gyral crowns, averaged by cerebral lobe (Fig. 1). We tested for group differences (soccer vs. non-collision athlete) and for the association of heading with longitudinal change of FA within the fundi and crowns over 2 years within the soccer player group.

RESULTS

65 soccer players and 75 age- and sex-matched control non-collision athletes were included in the analyses. Mean FA within sulcal fundi was lower amongst soccer players than non-collision athletes in five brain regions: frontal (P=2.04×10^-5), orbitofrontal (P=5.26×10^-11) (Fig. 2), cingulate (P=2.83×10^-3), temporal (P=1.96×10^-4), and parietal (P=7.39×10^-6). FA within the occipital region did not significantly differ (P=0.92). Similarly, FA was significantly lower within the gyral crowns of soccer players for the frontal (P=1.76×10^-4), orbitofrontal (P=5.15×10^-6), and temporal (P=5.03×10^-6) regions. The parietal (P=0.11) and cingulate (P=0.87) regions did show group differences. Change in FA over two years within soccer players (n=363) showed heading was significantly associated with a decrease in FA in the sulcal fundi of the frontal (P=4.5×10^-4), orbitofrontal (P=1.81×10^-3), occipital (P=3.34×10^-3), parietal (P=1.3×10^-5), temporal (P=2.1×10^-5), and cingulate (P=0.025) regions. A similar significant negative relationship was observed for heading and FA within the gyral crowns of the frontal (P=9.8×10^-5), orbitofrontal (P=1.7×10^-3), occipital (P=1.2×10^-4), parietal (P=2.5×10^-4), and temporal (P=5.3×10^-4) regions. Cingulate was not significant (P=0.772).

DISCUSSION

We identify an exposure-dependent relationship of soccer heading with lower FA within the sulcal fundi and gyral crowns. DTI may therefore identify regions of white matter microstructure changes that could co-locate with areas affected by phosphorylated tau pathology in RHI. The greater preponderance of lower FA in fundi and crowns within anterior regions of the brain is consistent with biomechanics of heading. The more widespread FA decreases within sulcal fundi compared to gyral crowns provides a preliminary clue that DTI may reveal the predilection of the depths of sulci to injury suggested by finite element modelling³ and post-mortem neuropathology⁴.

CONCLUSION

Compared to matched non-collision athletes, adult amateur soccer players with high soccer heading exposure show lower FA within the sulcal fundi and gyral crowns, and also show decline of FA at these locations over two years. These findings in you otherwise healthy players suggest an in vivo MRI signature of pathologic findings reported due to RHI post mortem, could represent an early stage of the evolution of RHI-associated pathology and warrant further investigation.

Acknowledgements

The Dana Foundation David Mahoney Neuroimaging Program, and the National Institute of Neurological Disorders and Stroke (R01NS082432 and R01NS123374).

References

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