A prospective diffusion tensor imaging study in mild traumatic brain injury

Abstract

Objectives: Only a handful of studies have investigated the nature, functional significance, and course of white matter abnormalities associated with mild traumatic brain injury (mTBI) during the semi-acute stage of injury. The present study used diffusion tensor imaging (DTI) to investigate white matter integrity and compared the accuracy of traditional anatomic scans, neuropsychological testing, and DTI for objectively classifying mTBI patients from controls.

Methods: Twenty-two patients with semi-acute mTBI (mean = 12 days postinjury), 21 matched healthy controls, and a larger sample (n = 32) of healthy controls were studied with an extensive imaging and clinical battery. A subset of participants was examined longitudinally 3-5 months after their initial visit.

Results: mTBI patients did not differ from controls on clinical imaging scans or neuropsychological performance, although effect sizes were consistent with literature values. In contrast, mTBI patients demonstrated significantly greater fractional anisotropy as a result of reduced radial diffusivity in the corpus callosum and several left hemisphere tracts. DTI measures were more accurate than traditional clinical measures in classifying patients from controls. Longitudinal data provided preliminary evidence of partial normalization of DTI values in several white matter tracts.

Conclusions: Current findings of white matter abnormalities suggest that cytotoxic edema may be present during the semi-acute phase of mild traumatic brain injury (mTBI). Initial mechanical damage to axons disrupts ionic homeostasis and the ratio of intracellular and extracellular water, primarily affecting diffusion perpendicular to axons. Diffusion tensor imaging measurement may have utility for objectively classifying mTBI, and may serve as a potential biomarker of recovery.

Figure 1 Fractional anisotropy (FA) values from all regions of interest (ROI) This figure presents the mean FA values from all ROI for the mild traumatic brain injury patients (mTBI; green bars) and healthy controls (HC; gray bars) for visit 1 (A) corrected for differences in premorbid intelligence estimates. ROI included the genu (GNU), body (BDY), and splenium (SPL) of the corpus callosum (CC), the superior corona radiata (SCR), the superior longitudinal fasciculus (SLF), the uncinate fasciculus (UF), the corona radiata (CR), and the internal capsule (IC). Significant effects are denoted with double asterisks, statistical trends with a single asterisk. (B) Axial diffusivity (AD) and radial diffusivity (RD) measurements for mTBI patients and HC for regions exhibiting statistical differences in FA. For the y-axis, the units of FA are dimensionless, whereas axial diffusivity and RD are equivalent to mm²/s.

Figure 2 Variability in mean fractional anisotropy (FA) between right and left hemisphere regions of interest (ROI) A measurement of variability in mean FA values between right and left hemisphere homologue ROI for the mild traumatic brain injury patients (mTBI; green bars) and healthy controls (HC; gray bars) corrected for differences in premorbid intelligence estimates. ROI included the superior longitudinal fasciculus (SLF), the uncinate fasciculus (UF), the corona radiata (CR), and the internal capsule (IC). Significant effects are denoted with double asterisks, statistical trends with a single asterisk.

Figure 3 Fractional anisotropy (FA) and radial diffusivity (RD) values at both visits Mean FA and RD for the mild traumatic brain injury patients (mTBI; green bars = visit 1, black bars = visit 2) and healthy controls (HC; gray bars = visit 1, brown bars = visit 2). Analyses were limited to ROI that displayed significant effects at visit 1, and included the left superior corona radiata (SCR), the left uncinate fasciculus (UF), the left internal capsule (IC), the left corona radiata (CR), the genu (GNU), and the splenium (SPL). For the y-axis, the units of FA are dimensionless, whereas RD is equivalent to mm²/s.