Diffusion Tensor Imaging Reveals Elevated Diffusivity of White Matter Microstructure that Is Independently Associated with Long-Term Outcome after Mild Traumatic Brain Injury: A TRACK-TBI Study

Abstract

Diffusion tensor imaging (DTI) literature on single-center studies contains conflicting results regarding acute effects of mild traumatic brain injury (mTBI) on white matter (WM) microstructure and the prognostic significance. This larger-scale multi-center DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a cohort study at 11 United States level 1 trauma centers, a total of 391 patients with acute mTBI ages 17 to 60 years were included and studied at two weeks and six months post-injury. Demographically matched friends or family of the participants were the control group (n = 148). Axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were the measures of WM microstructure. The primary outcome was the Glasgow Outcome Scale Extended (GOSE) score of injury-related functional limitations across broad life domains at six months post-injury. The AD, MD, and RD were higher and FA was lower in mTBI versus friend control (FC) at both two weeks and six months post-injury throughout most major WM tracts of the cerebral hemispheres. In the mTBI group, AD and, to a lesser extent, MD decreased in WM from two weeks to six months post-injury. At two weeks post-injury, global WM AD and MD were both independently associated with six-month incomplete recovery (GOSE <8 vs = 8) even after accounting for demographic, clinical, and other imaging factors. DTI provides reliable imaging biomarkers of dynamic WM microstructural changes after mTBI that have utility for patient selection and treatment response in clinical trials. Continued technological advances in the sensitivity, specificity, and precision of diffusion magnetic resonance imaging hold promise for routine clinical application in mTBI.

Keywords: Glasgow Outcome Scale; MRI; concussion; diffusion tensor imaging; traumatic brain injury.

FIG. 1.

CONSORT diagram for inclusion of enrolled TRACK-TBI patients into this analysis. TBI, traumatic brain injury; MRI, magnetic resonance imaging; DTI, diffusion tensor imaging; GCS, Glasgow Coma Scale; QC, quality control.

FIG. 2.

Diffusion tensor imaging (DTI) of patients with mild traumatic brain injury (mTBI) (n = 391) at two weeks post-injury versus demographically matched controls (n = 148). For each DTI metric, 30 representative axial images are shown with the right side of the image corresponding to the left side of the brain. The red to yellow color scale indicates significantly greater DTI metric of mTBI compared with controls (p < 0.05) with brighter yellow colors denoting a greater level of statistical significance. The blue to light blue color scale denotes significantly lower DTI metric of mTBI compared with controls (p < 0.05), with lighter blue colors denoting a greater level of statistical significance. While higher axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) are widespread, the lower fractional anisotropy (FA) in mTBI versus the control group (FC) is less extensive. The posterior fossa showed group FA differences in the left posterior cerebral peduncle and at the decussation of the superior cerebellar peduncles.

FIG. 3.

Diffusion tensor imaging (DTI) of mild traumatic brain injury (mTBI) (n = 391) at two weeks versus six months after head trauma. Conventions are as in Figure 2. The blue to light blue color scale indicates a significantly lower DTI metric at the second time point compared with the first time point (p < 0.05), with lighter blue colors denoting a greater level of statistical significance. While lowered axial diffusivity (AD) over time is widespread, there is lowered mean diffusivity (MD) over time primarily in projection and commissural tracts. The posterior fossa also shows decreasing MD over time particularly in the midbrain including the decussation of the superior cerebellar peduncles. Fractional anisotropy (FA) and radial diffusivity (RD) showed no statistically significant longitudinal changes.

FIG. 4.

Diffusion tensor imaging (DTI) of mild traumatic brain injury (mTBI) with Glasgow Outcome Scale Extended (GOSE) = 8 at six months post-injury (n = 173) versus those with GOSE <8 at six months (n = 194). Conventions are as in Figure 2. The red to yellow color scale indicates a significantly higher DTI metric in the GOSE = 8 group compared with the GOSE <8 group (p < 0.05), with lighter yellow colors denoting a greater degree of statistical significance. The axial diffusivity (AD) is significantly higher throughout much of the white matter, especially the long association and projection tracts, in the GOSE = 8 group compared with the GOSE <8 group. In the posterior fossa, there was particular involvement of the superior cerebellar peduncles centered at their decussation. The significantly higher level of mean diffusivity (MD) in the GOSE = 8 versus GOSE <8 groups primarily involves long association and projection tracts, although with a left hemispheric predominance.