Dr. Manning et al. found cross-sectional and longitudinal changes in the white matter diffusion measures and resting-state functional MRI network connectivity in 73 concussion-free female rugby players compared with 31 age-matched female swimmers and rowers. They concluded that longitudinal changes occur in the microstructure and function of the brain in otherwise healthy, asymptomatic athletes participating in contact sport and that further research is needed to understand the long-term brain health and biological implications of these changes. In response, Drs. Shahim and Diaz-Arrastia note that repetitive head impacts over decades have been associated with late-life dementia in previous studies of professional contact-sport athletes, but that it is less clear whether participation in such sports at the amateur level poses similar risks. They note that the finding of white matter microstructural disruption seen in the study by Dr. Manning et al. is also seen as a consequence of more severe traumatic brain injuries. While commending the longitudinal data provided by the study, they caution that imaging techniques such as diffusion tensor imaging and rsfMRI may detect small degrees of disruption that are not functionally limiting and also have limited availability and cumbersome processing needs that preclude their use for routine assessment of athletes. They call for further studies of more inexpensive blood-based biomarkers and their correlation with imaging markers of axonal disruption after concussive and subconcussive head impacts. Responding to these comments, the authors agree that cognitive reserve in the individuals studies may be sufficiently high that they are functionally unaffected by the identified MRI markers of tissue and network disruption but argue that they may eventually affect the brain’s response to other insults later in life. They agree that these MRI approaches are presently intended for research purposes. Noting that they have undertaken further work on blood-based markers on this cohort, they comment that metabolomic signatures may be more relevant than classical markers of injury while acknowledging the need for better correlation with imaging results and cognitive testing. This exchange underscores our evolving, but incomplete, understanding of the clinical significance of imaging and blood-based markers of axonal injury in otherwise healthy athletes engaged in contact sports.