Objective:

To examine the relationship between traumatic brain injury (TBI) and a biomarker of glymphatic function, diffusion tensor image analysis along the perivascular space (DTI-ALPS).

Background:

The glymphatic system is responsible for waste drainage via the movement of fluids along the perivascular spaces. Dysfunction of the glymphatic system is implicated in several neurological conditions but has not been well-studied in human TBI. The DTI-ALPS index has been proposed as a noninvasive biomarker of glymphatic function.

Design/Methods:

DTI was performed in patients with TBI at 2-weeks and 6-months post-injury, as well as in demographically matched healthy controls. Regions-of-interest were manually placed in the major fiber bundles at the level of the lateral ventricles, where they are orthogonal to perivascular spaces. DTI-ALPS index was computed by normalizing diffusivity along the orientation of these perivascular spaces to diffusivity in the perpendicular direction.

Results:

85 individuals with TBI (mean age 38.5 years, 73% male, 86% mild TBI) and 44 controls (31.6 years, 61% male) were included. Pearson’s correlation analyses revealed a significant negative correlation between DTI-ALPS and age (r = -0.313, p = 0.0035). There was no relationship with sex, Glasgow Coma Scale, or head CT status. Compared to controls (1.61 ± 0.16), DTI-ALPS at 2-weeks (1.56 ± 0.19) and 6-months post-TBI (1.58 ± 0.22) was not significantly different (p > 0.05). Additionally, the subset of individuals with a 6-month scan (n=43) showed no significant change over time in DTI-ALPS (p > 0.05).

Conclusions:

We did not find evidence for glymphatic system dysfunction associated with primarily mild TBI in the subacute post-injury period using the DTI-ALPS index in the periventricular white matter. Further research is necessary to ascertain whether glymphatic dysfunction is present in moderate to severe TBI or whether more global assessments identify subtle glymphatic dysfunction in milder TBI.