Multifocal White Matter Ultrastructural Abnormalities in Mild Traumatic Brain Injury with Cognitive Disability: A Voxel-Wise Analysis of Diffusion Tensor Imaging

Abstract

The purpose of the present study is to identify otherwise occult white matter abnormalities in patients suffering persistent cognitive impairment due to mild traumatic brain injury (TBI). The study had Institutional Review Board (IRB) approval, included informed consent and complied with the U.S. Health Insurance Portability and Accountability Act (HIPAA) of 1996. We retrospectively analyzed diffusion tensor MRI (DTI) of 17 patients (nine women, eight men; age range 26-70 years) who had cognitive impairment due to mild TBI that occurred 8 months to 3 years prior to imaging. Comparison was made to 10 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) images derived from DTI (1.5 T; 25 directions; b = 1000) were compared using whole brain histogram and voxel-wise analyses. Histograms of white matter FA show an overall shift toward lower FA in patients. Areas of significantly decreased FA (p < 0.005) were found in the subject group in corpus callosum, subcortical white matter, and internal capsules bilaterally. Co-located elevation of mean diffusivity (MD) was found in the patients within each region. Similar, though less extensive, findings were demonstrated in each individual patient. Multiple foci of low white matter FA and high MD are present in cognitively impaired mild TBI patients, with a distribution that conforms to that of diffuse axonal injury. Evaluation of single subjects also reveals foci of low FA, suggesting that DTI may ultimately be useful for clinical evaluation of individual patients.

Voxel-Based Analysis of Diffusion Tensor Imaging in Mild Traumatic Brain Injury in Adolescents

“…Thus, DTI findings in acute mTBI differ from what is typically seen in more chronic TBI, wherein DTI-defined WM abnormalities reflect degenerative changes. 20 Lipton et al 4 have shown that in adults with mTBI and lasting cognitive sequelae, nonspecific WM changes were observed that were similar to those in reports of nonspecific sub-cortical WM changes in more severe TBI but to a lesser degree. Nonetheless, the detected chronic WM lesions associated with mTBI were widespread.…”

“…Findings suggest that the effects of mTBI are indeed widespread, consistent with the distribution of DTI abnormalities observed during the chronic phase following mTBI. [4][5][6]34 Given that the participants were all scanned within 6 days of injury, it is plausible that some of these acute abnormalities may evolve into more chronic WM changes. Longitudinal DTI investigation of patients with mTBI is underway to evaluate this further.…”

“…However, DTI and other advanced MR imaging methods, such as susceptibility-weighted imaging, offer better detection of traumarelated injury occurring from shearing forces within brain parenchyma, and they have demonstrated a variety of consistent abnormalities across a number of mTBI studies. [1][2][3][4][5][6][7] Detailed biomechanical and heuristics studies consistently show the vulnerability of WM, particularly the CC and longcoursing fasciculi, especially within frontotemporal regions. [8][9][10][11][12] DTI abnormalities within the CC in patients with TBI have been well documented in both the acute and chronic phase of injury.…”

A Longitudinal Diffusion Tensor Imaging Study Assessing White Matter Fiber Tracts after Sports-Related Concussion

“…24 WM abnormalities have also been shown 25 in patients with mTBI exhibiting persistent cognitive impairment (8 months to 3 years postinjury). The latter investigators demonstrated decreased FA and increased MD in the corpus callosum (CC), bilateral capsula interna (CI), and other subcortical WM structures.…”

Emerging Imaging Tools for Use with Traumatic Brain Injury Research

“…Studies of TBI using DTI, as well as the software to analyze these data, have been steadily increasing in recent years. Significant differences in the FA, ADC, or MD, or other DTIderived diffusivity metrics have been demonstrated in studies of TBI in both adults (Bigler et al, 2010b;Kraus et al, 2007;Lipton et al, 2008;Perlbarg et al, 2009;Warner et al, 2010a) and children (Ewing-Cobbs et al, 2008;Levin et al, 2008;McCauley et al, 2011;Wilde et al, 2006bWilde et al, , 2010Wozniak et al, 2007;Wu et al, 2010a;Yuan et al, 2007), with decreases in FA and increases in measures of diffusivity often found in chronic post-injury intervals. More importantly, changes in DTIderived measures have shown correlation with injury severity (Arfanakis et al, 2002;Benson et al, 2007;Wilde et al, 2010;Yuan et al, 2007), functional outcome (Huisman et al, 2004;Levin et al, 2008;Salmond et al, 2006;Wozniak et al, 2007), neurologic functioning (Caeyenberghs et al, 2010a,b), and cognitive ability (Bigler et al, 2010b;Ewing-Cobbs et al, 2008;Kraus et al, 2007;Kumar et al, 2009;Levin et al, 2008;McCauley et al, 2011;Niogi et al, 2008;Salmond et al, 2006;Warner et al, 2010a;Wilde et al, 2010).…”