Changes In Serum Neurofilament Light And Brain White Matter Microstructure In Female Football Players: A Pilot Study

Abstract

Repeated mechanical loading of the head can cause axonal damage in a dose-dependent manner. The corpus callosum (CC), a thick commissural white matter tract, is believed to be particularly sensitive to this loading. Neurofilament light (NfL) has emerged as a blood-based biomarker that is sensitive to axonal damage and may be useful for monitoring athlete brain health. However, the source of circulating NfL in contact and collision sport athletes who may have sustained axonal damage due to mechanical loading of the head, but have not been diagnosed with a brain injury, is poorly understood. PURPOSE: To compare changes in serum NfL to changes in corpus callosum (CC) microstructure over a single season of competition. METHODS: Semi-professional female tackle football players (n = 5) had blood drawn (8.5 mL) and underwent diffusion MRI (64 directions, bval = 1300 s/mm2) and structural MRI (T1w, MPRAGE) before and after their season (4 games and 39 practices over 12 weeks). Despite that no participant reported a medical diagnosis of concussion during the season, participants were asked to report the presence and degree of concussion-related symptoms at each time point using the Rivermead Post-Concussion Questionnaire. Serum samples were assayed for (NfL) at pre and post season time points. The CC was reconstructed for each participant from preprocessed diffusion MRI data using automatic fiber tracking and atlas-guided tract recognition with bilateral cerebellar hemispheres as regions of avoidance (DSI Studio). Microstructural metrics were computed from these reconstructed tracts to represent CC integrity. RESULTS: Increases in NfL were associated with increases in CC radial diffusivity (r2 = .845) and decreases in CC quantitative anisotropy (r2 = .675) and fractional anisotropy (r2 = .967). Changes in NfL and CC integrity were moderately related to changes in concussive symptoms (r2 = .366-.772). CONCLUSIONS: The relationships observed in these preliminary data suggest that changes in serum NfL may be sufficiently sensitive to detect subclinical, ‘subconcussive’ axonal injuries in collision sport athletes.