White Matter Perivascular Space Burden Is Associated With Mild Traumatic Brain Injury History In Soldiers

Abstract

Mild traumatic brain injury (mTBI) exposure in military Service Members may lead to impaired brain waste clearance which increases neurological disease risk including amyloidopathies. Perivascular spaces (PVS) are part of the glymphatic pathway which support brain waste clearance, especially during sleep. Greater magnetic resonance imaging (MRI)-visible PVS burden has been previously observed in patients with neurodegenerative diseases and animal TBI models. PURPOSE: To determine the association between PVS burden (number and volume) and mTBI history in Special Operations Forces (SOF) combat Soldiers. METHODS: In this cross-sectional study, participants underwent neuroimaging to capture T2-weighted (T2w) whole brain three dimensional volumes obtained on a Siemens 3T Biograph mMR or 3T MAGNETOM Prisma scanner (TR/TE = 3200/400ms, slice thickness = 1mm, FoV = 256mm x 256 mm). The PVS segmentation was performed using a previously validated, multi-scale deep convolutional encoder-decoder neural network. All T2w images were skull stripped and a custom T2w atlas with segmented cerebral white matter and subcortical gray matter labels was registered to each subject using Advanced Normalization Tools to minimize misidentifying thin tubular structures in the skull, brainstem, cerebellum, and cortex as PVS. Only PVS clusters within the white matter mask were quantified for analyses. Binary mTBI history was self-reported (“yes” or “no”). Due to non-normal PVS metric distribution, non-parametric Mann-Whitney U tests were used to determine group differences in PVS outcomes. RESULTS: In total, 223 healthy SOF combat Soldiers (age = 33.1±4.3yrs) were included for analysis and 123 (55.16%) reported mTBI history. Soldiers with mTBI history had greater PVS number (z = 2.506, P = 0.013) and PVS volume (z = 2.419, P = 0.016). CONCLUSIONS: We found mTBI history is associated with increased PVS burden in SOF combat Soldiers that are clinically recovered from mTBI. This may indicate ongoing physiological post-mTBI changes that could lead to impaired waste clearance via the glymphatic system. Future studies should determine how sleep influences PVS burden following mTBI exposure and if PVS number and volume are meaningful neurobiological outcomes for neurodegenerative disease risk. Funded by US Special Operations Command