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Longitudinal QSM imaging reveals disrupted subcortical white matter maturation in football vs volleyball college athletes1Stanford University School of Medicine, Stanford, CA, United States, 2Weill Cornell Medical College, New York, NY, United States
Synopsis
Keywords: Traumatic brain injury, Quantitative Susceptibility mapping
Head impacts in sports may cause long-term brain changes. Here, we assessed quantitative susceptibility mapping (QSM) changes over multiple seasons in high-contact American football vs low-contact volleyball college athletes using the multi-echo complex total field inversion (mcTFI) method. We found widespread changes over time (likely developmental) in all athletes, while time-independent sports differences were detected by R2*. mcTFI revealed an altered QSM trajectory in the white matter (total and subcortical) between sports: QSM increased in volleyball athletes but changed minimally in football, likely indicating disrupted subcortical white matter maturation in football. QSM can sensitively detect longitudinal changes in contact sports.Introduction
Head injuries are very common and have devastating health, economic, and societal consequences1. Head impacts from contact sports such as college American football, even without concussion2, may alter athletes’ brains, possibly leading to neurological impairment3, while players largely underestimate risks4. Quantitative susceptibility mapping (QSM), a method sensitive to tissue’s magnetic susceptibility, is a promising tool for investigating brain injury5–7. Here, we report longitudinal QSM results on high-contact (football) vs low-contact (volleyball) college athletes over multiple seasons of play.Methods
Subjects: We analyzed imaging data from 49 football and 24 volleyball athletes (268 scans with up to 4 years of followup), see Fig. 1. Athletes were scanned at each season’s start, and after their last season of sport participation.Imaging: Using a 3T GE-MR750 scanner with an 8-channel receive head coil, we acquired (1) T1-weighted images (inversion recovery fast spoiled gradient echo) with TR=7.9ms, TE= 3.1ms, NEX=1, 1mm isotropic, and (2) an axial 3D multi-echo gradient echo sequence (ME-GRE), with 8 TEs (5-40ms, 5ms spacing), TR=45ms, FA 15o, BW 62, frequency S/I, flow compensation, 1mm isotropic, matrix 256x218x256, ARC 2x2.
Data processing: T1w images were segmented using the FreeSurfer 5.3 longitudinal pipeline as previously described8. Mean magnitude images from the ME-GRE were registered to T1w images using Freesurfer’s bbregister. The freesurfer segmentation was then transformed to ME-GRE space. QSM and R2* were calculated using the recently-developed multi-echo complex total field inversion (mcTFI) method9, Fig. 2, which provides robust results compared to alternative methods10,11. Images were manually inspected both for quality, segmentation, and coregistration between T1w and ME-GRE. Median mcTFI QSM and R2* values per Freesurfer regions were computed, and a linear-mixed-effects (LME) model in Stata-15 was used to study longitudinal changes after combining regions into larger compartments (e.g. combining first across hemispheres, then across regions within a lobe of the brain, etc. as in 8). Sport, time, and their interaction were considered fixed effects, while subjects were random effects.
Results
Altered trajectories in football vs volleyball players white matter revealed by QSM: The LME model revealed significantly different trajectories of QSM values in the white matter of football vs volleyball athletes over time, Fig. 3: the total white matter QSM values of volleyball players increase over time, whereas the ones of football players are almost stable, increasing with very small slope, Fig. 3A. This effect seems to be mainly driven by the QSM changes in subcortical white matter, Fig. 3B. Similar longitudinal trends (volleyball athlete values changing more than football ones), yet not statistically significantly different between sports, were identified in the mcTFI QSM values in other white and gray matter regions too, cf Fig. 4.Longitudinal differences in white and gray matter over time in both sports: QSM values in total white and gray matter of both football and volleyball players seemed to change significantly over time, Figs. 3,4. This effect was also present in various white and gray matter subregions, including subcortical white matter Fig. 3B, middle frontal, pre- and para-central and cerebellum white matter, Fig. 4A, and both cortical and deep gray matter, Fig. 4B. Similar differences over time (but in fewer regions) were also captured by R2*, Fig. 5.
Time-independent changes in football vs volleyball athlete brains detected by R2*: Apart from the R2* time effect, there was also a significant football vs volleyball difference in white and gray matter R2* values independent of time, Fig. 5. Specifically, the football players had higher R2* values in total white and gray matter, and multiple subregions (subcortical white matter and corpus callosum, total cortical and frontal gray matter), with the effect being stronger in white than in gray matter. Volleyball vs football R2* trajectories over time were not significantly different.
Discussion
Few previous studies investigated QSM changes in athletes. Gong et al. reported no QSM changes after a high-school football season12, and Weber et al. found no concussion-related QSM changes in hockey players. Koch et al. reported white matter QSM changes in high-school football athletes post-concussion13, and Brett et al. found that years of exposure predicted white matter QSM changes in high-school and college football and soccer athletes14.Using our LME model across white and gray matter, we detected differential QSM (but not R2*) trajectories in the white matter (especially subcortical) of football vs volleyball athletes, with QSM values increasing considerably in volleyball but very little in football. Given that subcortical connections undergo late myelination15, which requires a lot of iron16, there may be a disrupted subcortical myelination in high-contact football compared to low-contact volleyball athletes. Such hypothesis is also supported by our previously reported slower cortical thinning8 and microstructural white matter trajectories17 in football vs volleyball athletes.
We also found sport (football vs volleyball) R2* differences in white and gray matter, but these are mostly due to baseline differences, and it is unclear if they are caused by development, prior impacts, or other reasons. Increases in QSM and R2* values over time in white and gray matter in both sports possibly reflect normal developmental changes in this age range18–22, consistent with our hypothesis.
Conclusion
QSM can detect longitudinal changes in high- vs low-contact sports that could be related to abnormal white-matter development.Acknowledgements
Research was supported by the National Institutes of Health (NIH) award number R01AG061120-01.References
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