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Test for a dose dependent relationship between cumulative sub-concussive head trauma loading and localised changes of brain white matter in college athletes.Prospective cohort studyNCAA Division I Women’s Soccer10 players were monitored for head impacts throughout a soccer season using wearable sensors. Linear and rotational accelerations recorded during impacts were processed to calculate the cumulative impact power. Diffusion spectrum imaging (DSI) data were acquired at season start and at 3 additional intervals. 11 age and gender matched control data sets were acquired.One athlete suffered a concussion, was removed from play for neurocognitive testing, and entered a supervised return-to-play protocol.Cumulative impact power was used as a measure of the head trauma load accumulated prior to each MRI. Multi-dimensional anisotropy (MDA) values assessed localised severity of white matter changes. Session specific differences between each player’s MDA values and those of the control population were used to relate cumulative impact power and the severity of white matter changes.Highly significant clusters of abnormal voxels were observed in athletes with no diagnosed concussion symptoms. Injury severity correlated with cumulative head impact power and demonstrated a pronounced threshold behaviour. MDA diffusion changes were located mainly within the frontal and occipital cortex at the gray-white boundary, and to a lesser degree in deep subcortical areas where there is a higher proportion of crossing fibres.This cohort demonstrates dose dependent changes in white matter integrity as a function of cumulative sub-concussive head trauma.SG is supported, in part, by a research grant from X2 Biosystems and a General Electric-National Football League Head Health Challenge award.