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...

Single-voxel proton magnetic resonance imaging (1H-MRS) and proton MR spectroscopic imaging (1H-MRSI) were used to compare brain metabolite levels in semi-acute mild traumatic brain injury (mTBI) patients (n = 10) and matched healthy controls (n = 9). The 1H-MRS voxel was positioned in the splenium, a region known to be susceptible to axonal injury in TBI, and a single 1H-MRSI slice was positioned above the lateral ventricles. To increase sensitivity to the glutamate (Glu) and the combined glutamate-glutamine (Glx) signal, an inter-pulse echo time shown to emphasize the major Glu signals was used along with an analysis method that reduces partial volume errors by using water as a concentration standard. Our preliminary findings indicate significantly lower levels of gray matter Glx and higher levels of white matter creatine-phosphocreatine (Cr) in mTBI subjects relative to healthy controls. Furthermore, Cr levels were predictive of executive function and emotional distress in the combined groups. These results suggest that perturbations in Cr, a critical component of the brain’s energy metabolism, and Glu, the brain’s major neurotransmitter, may occur following mTBI. Moreover, the different pattern of results for gray and white matter suggests tissue-specific metabolic responses to mTBI.

Despite the prevalence and impact of mild traumatic brain injury (mTBI), common clinical assessment methods for mTBI have insufficient sensitivity and specificity. Moreover, few researchers have attempted to document underlying changes in physiology as a function of recovery from mTBI. Proton magnetic resonance spectroscopy (¹H-MRS) was used to assess neurometabolite concentrations in a supraventricular tissue slab in 30 individuals with semi-acute mTBI, and 30 sex-, age-, and education-matched controls. No significant group differences were evident on traditional measures of attention, memory, working memory, processing speed, and executive skills, though the mTBI group reported significantly more somatic, cognitive, and emotional symptoms. At a mean of 13 days post-injury, white matter concentrations of creatine (Cre) and phosphocreatine (PCre) and the combined glutamate-glutamine signal (Glx) were elevated in the mTBI group, while gray matter concentrations of Glx were reduced. Partial normalization of these three neurometabolites and N-acetyl aspartate occurred in the early days post-injury, during the semi-acute period of recovery. In addition, 17 mTBI patients (57%) returned for a follow-up evaluation (mean = 120 days post-injury). A significant group × time interaction indicated recovery in the mTBI group for gray matter Glx, and trends toward recovery in white matter Cre and Glx. An estimate of premorbid intelligence predicted the magnitude of neurometabolite normalization over the follow-up interval for the mTBI group, indicating that biological factors underlying intelligence may also be associated with more rapid recovery.

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The semi-acute phase of mild traumatic brain injury (mTBI) is associated with deficits in the cognitive domains of attention, memory, and executive function, which previous work suggests may be related to a specific deficit in disengaging attentional focus. However, to date there have only been a few studies that have employed dynamic imaging techniques to investigate the potential neurological basis of these cognitive deficits during the semi-acute stage of injury. Therefore, event-related functional magnetic resonance imaging (FMRI) was used to investigate the neurological correlates of attentional dysfunction in a clinically homogeneous sample of 16 mTBI patients during the semi-acute phase of injury (< 3 weeks). Behaviorally, mTBI patients exhibited deficits in disengaging and reorienting auditory attention following invalid cues as well as a failure to inhibit attentional allocation to a cued spatial location compared to a group of matched controls. Accordingly, mTBI patients also exhibited hypoactivation within thalamus, striatum, midbrain nuclei and cerebellum across all trials as well as hypoactivation in the right posterior parietal cortex, pre-supplementary motor area, bilateral frontal eye fields and right ventrolateral prefrontal cortex during attentional disengagement. Finally, the hemodynamic response within several regions of the attentional network predicted response times better for controls than mTBI patients. These objective neurological findings represent a potential biomarker for the behavioral deficits in spatial attention that characterize the initial recovery phase of mTBI.

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Single-voxel proton magnetic resonance imaging ((1)H-MRS) and proton MR spectroscopic imaging ((1)H-MRSI) were used to compare brain metabolite levels in semi-acute mild traumatic brain injury (mTBI) patients (n = 10) and matched healthy controls (n = 9). The (1)H-MRS voxel was positioned in the splenium, a region known to be susceptible to axonal injury in TBI, and a single (1)H-MRSI slice was positioned above the lateral ventricles. To increase sensitivity to the glutamate (Glu) and the combined glutamate-glutamine (Glx) signal, an inter-pulse echo time shown to emphasize the major Glu signals was used along with an analysis method that reduces partial volume errors by using water as a concentration standard. Our preliminary findings indicate significantly lower levels of gray matter Glx and higher levels of white matter creatine-phosphocreatine (Cr) in mTBI subjects relative to healthy controls. Furthermore, Cr levels were predictive of executive function and emotional distress in the combined groups. These results suggest that perturbations in Cr, a critical component of the brain's energy metabolism, and Glu, the brain's major neurotransmitter, may occur following mTBI. Moreover, the different pattern of results for gray and white matter suggests tissue-specific metabolic responses to mTBI.

No abstract