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.

Chronic traumatic encephalopathy: Diagnostic updates and advances

“…As such, decreased FA, decreased AD and increased RA would be expected in CTE due to decreased white matter integrity. These findings have been demonstrated in mTBI, and even had prognostic value [39] – [47] . A post-mortem tissue DTI analysis of patients with confirmed CTE-NC by Holleran et al demonstrated associations between decreased FA and reduced white matter integrity [38] .…”

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

“…Another method to reduce the limitations of multimodal imaging is the creation of longitudinal prospective multi-institutional studies to standardize imaging techniques and link acute imaging results with long-term functional outcomes. One such example is the TRACK-TBI study, which has leveraged this model to uncover early multimodal imaging markers in mTBI that predict long-term outcomes [ 193 ]. Furthermore, the data generated by studies like TRACK-TBI can be used to train, validate, and test machine learning models to uncover prognostic insights into TBI physiology that could be used to guide treatment.…”

Multi-mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

“…Another method to reduce the limitations of multimodal imaging is the creation of longitudinal prospective multi-institutional studies to standardize imaging techniques and link acute imaging results with long-term functional outcomes. One such example is the TRACK-TBI study, which has leveraged this model to uncover early multimodal imaging markers in mTBI that predict long-term outcomes [156]. Furthermore, the data generated by studies like TRACK-TBI can be used to train, validate and test machine learning models to uncover prognostic insights into TBI physiology that could be used to guide treatment.…”