Assessing Postconcussive Reaction Time Using Transport-Based Morphometry of Diffusion Tensor Images

Abstract

Background and purpose: Cognitive deficits are among the most commonly reported post-concussive symptoms, yet the underlying microstructural injury is poorly understood. Our aim was to discover white matter injury underlying reaction time in mild traumatic brain injury DTI by applying transport-based morphometry.

Materials and methods: In this retrospective study, we performed DTI on 64 postconcussive patients (10-28 years of age; 69% male, 31% female) between January 2006 and March 2013. We measured the reaction time percentile by using Immediate Post-Concussion Assessment and Cognitive Testing. Using the 3D transport-based morphometry technique we developed, we mined fractional anisotropy maps to extract the common microstructural injury associated with reaction time percentile in an automated manner. Permutation testing established statistical significance of the extracted injuries. We visualized the physical substrate responsible for reaction time through inverse transport-based morphometry transformation.

Results: The direction in the transport space most correlated with reaction time was significant after correcting for covariates of age, sex, and time from injury (Pearson r = 0.44, P < .01). Inverting the computed direction using transport-based morphometry illustrates physical shifts in fractional anisotropy in the corpus callosum (increase) and within the optic radiations, corticospinal tracts, and anterior thalamic radiations (decrease) with declining reaction time. The observed shifts are consistent with biologic pathways underlying the visual-spatial interpretation and response-selection aspects of reaction time.

Conclusions: Transport-based morphometry discovers complex white matter injury underlying postconcussive reaction time in an automated manner. The potential influences of edema and axonal loss are visualized in the visual-spatial interpretation and response-selection pathways. Transport-based morphometry can bridge the gap between brain microstructure and function in diseases in which the structural basis is unknown.

Fig 1.

FA maps of 10 different postconcussive patients. The same axial slice is shown for patients with the best reaction time percentiles (upper row) and worst reaction time percentiles (lower row). These images illustrate the challenge that FA maps corresponding to the best and worst reaction times are not easily differentiated by visual inspection because the abnormal variations related to reaction time cannot be discerned from the other heterogeneous variations. Intelligent computer-aided techniques are needed to differentiate these images.

Fig 2.

Most correlated direction. Images corresponding to the most correlated direction in transport space show decreasing FA in the corticospinal tracts, anterior thalamic radiations, and optic radiations with the low reaction time percentile corresponding to the scatterplot in On-line Fig 3. The FA in the corpus callosum increases as reaction time decreases.

Fig 3.

TBM can help assess cognitive deficits in individual patients using the computed direction to assess whether the complex and spatially distributed patterns of white matter injury identified by Fig 2 are present. When transport maps are projected onto this direction, a projection score is generated that can be used to differentiate patients according to the relationship in On-line Fig 3. The subjects shown correspond to i = 3 and 4 in Fig 1. The direction of FA change with respect to the reference in individual patients corroborates the patterns identified in Fig 2.