Diffusion Tensor Imaging Along the Perivascular Space in Veterans with Remote Mild Traumatic Brain Injuries

We investigated the association between diffusion tensor imaging along the perivascular space (DTI-ALPS) and remote mild traumatic brain injury (mTBI) exposures in previously deployed, post-9/11 Veterans. DTI-ALPS is a noninvasive, magnetic resonance imaging (MRI)-based proxy of glymphatic flow. Participants were 140 consecutively enrolled Veterans from the Translational Research Center for TBI and Stress Disorders (TRACTS) Houston cohort at the Michael E. DeBakey VA Medical Center who completed MRI. TBI exposures were assessed with the Boston Assessment of TBI-Lifetime. Individuals with moderate or severe TBI were excluded. We analyzed relationships between the DTI-ALPS index, a ratio of diffusion measures at <i>a priori</i> regions of interest. Participants were median age of 35 (interquartile range = 31, 41) years, predominantly male (91.4%) and white race (56.6%). Age was negatively correlated with DTI-ALPS indices (Spearman's <i>r_s</i> -0.181, <i>p</i> = 0.032). DTI-ALPS indices significantly differed among participants with no TBI (18.6%; DTI-ALPS [M ± SD] = 1.59 ± 0.21), mTBI Grade I (26.4%; 1.65 ± 0.26), mTBI Grade II (45%; 1.72 ± 0.29), and mTBI Grade III (10%; 1.82 ± 0.26) exposures (analysis of variance <i>p</i> = 0.042). The Jonckheere-Terpstra (JT) test was significant (JT = 4117, <i>p</i> value = 0.003), demonstrating an ordinal relationship between DTI-ALPS and increasing mTBI severity. Multivariable linear regression modeling revealed that mTBI Grade III was significantly associated with higher DTI-ALPS (β = 0.209, 95% confidence interval [CI] 0.038, 0.38; <i>p</i> = 0.017) when compared with no TBI, whereas age was significantly associated with lower DTI-ALPS (β = -0.007, 95% CI -0.013, -0.001; <i>p</i> = 0.025). mTBI Grades I and II did not significantly differ from no TBI when considered independently. DTI-ALPS index scores increased with the severity of mTBI. This represents a novel investigation of persistent glymphatic markers associated with remote mTBI in Veterans with neuropsychiatric comorbidities. Future work is needed to understand the temporal progression of changes in glymphatic function following mTBI and whether the observed changes have clinical or functional impacts on Veterans' quality of life.