White Matter Abnormalities in Veterans With Mild Traumatic Brain Injury

Abstract

Objective It has been estimated that 10%–20% of U.S. veterans of the wars in Iraq and Afghanistan experienced mild traumatic brain injury (TBI), mostly secondary to blast exposure. Diffusion tensor imaging (DTI) may detect subtle white matter changes in both the acute and chronic stages of mild TBI and thus has the potential to detect white matter damage in patients with TBI. The authors used DTI to examine white matter integrity in a relatively large group of veterans with a history of mild TBI. Method DTI images from 72 veterans of the wars in Iraq and Afghanistan who had mild TBI were compared with DTI images from 21 veterans with no exposure to TBI during deployment. Conventional voxel-based analysis as well as a method of identifying spatially heterogeneous areas of decreased fractional anisotropy (“potholes”) were used. Veterans also underwent psychiatric and neuropsychological assessments. Results Voxel-based analysis did not reveal differences in DTI parameters between the veterans with mild TBI and those with no TBI. However, the veterans with mild TBI had a significantly higher number of potholes than those without TBI. The difference in the number of potholes was not influenced by age, time since trauma, a history of mild TBI unrelated to deployment, or coexisting psychopathology. The number of potholes was correlated with the severity of TBI and with performance in executive functioning tasks. Conclusions Veterans who had blast-related mild TBI showed evidence of multifocal white matter abnormalities that were associated with severity of the injury and with relevant functional measures. Overall, white matter potholes may constitute a sensitive biomarker of axonal injury that can be identified in mild TBI at acute and chronic stages of its clinical course.

Potholes and Molehills: Bias in the Diagnostic Performance of Diffusion-Tensor Imaging in Concussion

“…We replicated previously published methods for pothole analysis (2,(7)(8)(9), in which images D iagnosing mild traumatic brain injury (TBI) after concussion by using brain imaging is fundamentally a difficult problem; it requires that the effect of a single noncatastrophic event can be recognized as having distinct characteristics, as opposed to those caused by natural variation among the population amid a lifetime background of other minor insults. Further confounding this problem is the inherent heterogeneity of mild TBI, as the spatial distribution and magnitude of any effect are likely to vary markedly from one individual to another (1).…”

“…An alternative approach is that of "pothole" analysis. White et al introduced the concept of analyzing white matter potholes in a study of earlyonset schizophrenia (17), and this technique has been applied recently to white matter analysis in mild TBI (2,4,(7)(8)(9)(10). In this technique, the FA value at each voxel is transformed into a z statistic based on the mean and the standard deviation of FA in a reference population.…”

Cognitive and behavioral deficits arising from neurodegeneration and traumatic brain injury: a model for the underlying role of focal axonal swellings in neuronal networks with plasticity

“…FAS is a hallmark feature of TBI which is annually responsible for millions of hospitalizations, with at least 1.7 million cases in the United States alone [14,15]. Reports estimate that 57 million people worldwide experienced some form of TBI [16].…”

“…Reports estimate that 57 million people worldwide experienced some form of TBI [16]. It targeted around 15% of all veterans of the Iraq and Afghanistan wars, with blast injuries being the signature wound of these conflicts [15,16]. Numerous studies show that even mild concussions, if induced repeatedly, can lead to permanent brain damage; the issue is constantly debated in the sports media, but especially in football [17].…”

Traumatic Brain Injury Imaging Research Roadmap

“…In particular, when comparing groups of individuals having mild TBI with normal control subjects (as opposed to diagnosing mild TBI in an individual), these techniques have shown quantitative abnormalities in the brain related to subacute and long-term traumatic sequelae (eg, cognitive dysfunction), frequently in the absence of intracranial abnormalities detected by nonquantitative visual inspection alone on conventional neuroimaging methods. 19,25,[31][32][33][34][35][36][37][38][39][40][41][42] Such intriguing data suggest a potentially important clinical role for advanced imaging methods, especially in the large population of patients with mild TBI who are symptomatic but whose conventional neuroimaging examination shows no visible abnormality. In these cases, advanced neuroimaging techniques may hold the most promise as sensitive diagnostic and prognostic tools for identifying clinically relevant abnormalities that are otherwise imperceptible on conventional imaging.…”