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 ϭ 12 days postinjury), 21 matched healthy controls, and a larger sample (n ϭ 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.
Neurology® 2010;74:643-650 GLOSSARY ADC ϭ apparent diffusion coefficient; CC ϭ corpus callosum; CCI ϭ cortical impact injury model; CR ϭ corona radiata; DTI ϭ diffusion tensor imaging; EC ϭ external capsule; FA ϭ fractional anisotropy; FPI ϭ fluid percussion injury model; HC ϭ healthy controls; IC ϭ internal capsule; JHU ϭ Johns Hopkins University; MANCOVA ϭ multivariate analysis of covariance; mTBI ϭ mild traumatic brain injury; RD ϭ radial diffusivity; ROI ϭ region of interest; SCR ϭ superior corona radiata; SLF ϭ superior longitudinal fasciculus; UF ϭ uncinate fasciculus.Complex cognitive processes such as attention, executive functions, and memory depend on intact white matter tracts among frontal, parietal, and medial temporal lobes, 1 which are likely disrupted following mild traumatic brain injury (mTBI). Histologic evidence of white matter changes have been observed in both human autopsy 2,3 and animal 4 studies of mTBI. Although traditional neuroimaging sequences (i.e., T1-and T2-weighted imaging) are typically insensitive to these putative white matter changes, diffusion tensor imaging (DTI) is capable of measuring white matter pathology with histologic correlates in animal models of injury...