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 ϭ 0.44, P Ͻ .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 responseselection pathways. Transport-based morphometry can bridge the gap between brain microstructure and function in diseases in which the structural basis is unknown. ABBREVIATIONS: FA ϭ fractional anisotropy; ImPACT ϭ Immediate Post-Concussion Assessment and Cognitive Testing; mTBI ϭ mild traumatic brain injury; TBM ϭ transport-based morphometry C ognitive deficits are among the most commonly reported symptoms after mild traumatic brain injury (mTBI). 1-6 Both transient and persistent deficits in processing speed, attention, and working memory are associated with mTBI. 7 Furthermore, persistent cognitive deficits may accelerate aging-related cognitive decline. 2 Yet, despite its ubiquity, the microstructure underlying postconcussive cognitive deficit is difficult to assess. Routine CT and MR imaging findings are often negative. Although diffusion tensor imaging can capture diffuse white matter injury, 8 mTBI is still diagnosed clinically because damage is subtle and spatially diffuse. 7,9 The microstructural injury is challenging to

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