Diffusion tensor imaging for outcome prediction in mild traumatic brain injury: a TRACK-TBI study

Abstract

We evaluated 3T diffusion tensor imaging (DTI) for white matter injury in 76 adult mild traumatic brain injury (mTBI) patients at the semiacute stage (11.2±3.3 days), employing both whole-brain voxel-wise and region-of-interest (ROI) approaches. The subgroup of 32 patients with any traumatic intracranial lesion on either day-of-injury computed tomography (CT) or semiacute magnetic resonance imaging (MRI) demonstrated reduced fractional anisotropy (FA) in numerous white matter tracts, compared to 50 control subjects. In contrast, 44 CT/MRI-negative mTBI patients demonstrated no significant difference in any DTI parameter, compared to controls. To determine the clinical relevance of DTI, we evaluated correlations between 3- and 6-month outcome and imaging, demographic/socioeconomic, and clinical predictors. Statistically significant univariable predictors of 3-month Glasgow Outcome Scale-Extended (GOS-E) included MRI evidence for contusion (odds ratio [OR] 4.9 per unit decrease in GOS-E; p=0.01), ≥1 ROI with severely reduced FA (OR, 3.9; p=0.005), neuropsychiatric history (OR, 3.3; p=0.02), age (OR, 1.07/year; p=0.002), and years of education (OR, 0.79/year; p=0.01). Significant predictors of 6-month GOS-E included ≥1 ROI with severely reduced FA (OR, 2.7; p=0.048), neuropsychiatric history (OR, 3.7; p=0.01), and years of education (OR, 0.82/year; p=0.03). For the subset of 37 patients lacking neuropsychiatric and substance abuse history, MRI surpassed all other predictors for both 3- and 6-month outcome prediction. This is the first study to compare DTI in individual mTBI patients to conventional imaging, clinical, and demographic/socioeconomic characteristics for outcome prediction. DTI demonstrated utility in an inclusive group of patients with heterogeneous backgrounds, as well as in a subset of patients without neuropsychiatric or substance abuse history.

Keywords: axonal injury; computed tomography; diffusion tensor imaging; magnetic resonance imaging; traumatic brain injury.

FIG. 1.

Voxel-wise nonparametric statistical comparison between mild traumatic brain injury (mTBI) patients and controls, with corrections for multiple voxel-wise comparisons using threshold-free cluster enhancement. This analysis was used to compare (A) 76 mTBI patients to 50 controls, (B) the subgroup of 32 computed tomography/magnetic resonance imaging (CT/MRI)-positive mTBI patients to the 50 controls, and (C) the subgroup of 44 CT/MRI-negative patients to the 50 controls. Voxel clusters with statistically significant differences in fractional anisotropy (FA) between mTBI and control groups at p<0.05 are shown in red/orange/yellow, with yellow denoting greater statistical significance. (A) shows that the 76 mTBI patients demonstrated significantly lower FA in the genu of the corpus callosum, uncinate fasciculi, and anterior corona radiata bilaterally as well as right internal and external capsules, compared to the 50 control subjects. (B) In a comparison of a much smaller subgroup of 32 CT/MRI-positive mTBI patients to the 50 controls, areas of reduced FA were even more extensive and attained much higher levels of statistical significance (yellow regions, corresponding to p<0.01) than in the comparison of 76 mTBI patients to the control group (mostly red/orange areas, corresponding to p<0.05, in [A]). (C) shows that this method demonstrated no evidence for white matter injury in 44 CT/MRI-negative mTBI patients, compared to the 50 controls. Color image is available online at www.liebertpub.com/neu

FIG. 2.

Voxel-wise nonparametric statistical comparison between mild traumatic brain injury (mTBI) patients without previous history of substance abuse or other neuropsychiatric disorder and controls, with corrections for multiple voxel-wise comparisons using threshold-free cluster enhancement. This analysis was used to compare (A) 37 mTBI patients without pre-existing substance abuse or neuropsychiatric history to 50 controls, (B) the subgroup of 17 computed tomography/magnetic resonance imaging (CT/MRI)-positive mTBI patients to the 50 controls, and (C) the subgroup of 20 CT/MRI-negative patients to the 50 controls. Voxel clusters with statistically significant differences in fractional anisotropy (FA) between mTBI and control groups at p<0.05 are shown in red/orange/yellow, with yellow denoting greater statistical significance. (B) shows that CT/MRI-positive mTBI patients without substance abuse or neuropsychiatric history demonstrated significantly lower FA in the anterior and posterior limbs of the internal capsules, external capsules, uncinate fasciculi, genu of the corpus callosum, and anterior corona radiata bilaterally. In contrast, (C) shows that this method demonstrated no evidence for white matter injury in CT/MRI-negative mTBI. Color image is available online at www.liebertpub.com/neu