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Increased Gray Matter Diffusion Anisotropy in Patients with Persistent Post-concussive Symptoms following Mild Traumatic Brain Injury

Institution:
1Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA.
Publisher:
Public Library of Science
Publication Date:
Jun-2013
Journal:
PLoS One
Volume Number:
8
Issue Number:
6
Pages:
e66205
Citation:
PLoS One. 2013 Jun 11;8(6):e66205.
PubMed ID:
23776631
PMCID:
PMC3679020
Appears in Collections:
PNL, NA-MIC
Sponsors:
R01 MH082918/MH/NIMH NIH HHS/United States
R01 NS078337/NS/NINDS NIH HHS/United States
U54 EB005149/EB/NIBIB NIH HHS/United States
Generated Citation:
Bouix S., Pasternak O., Rathi Y., Pelavin P.E., Zafonte R., Shenton M.E. Increased Gray Matter Diffusion Anisotropy in Patients with Persistent Post-concussive Symptoms following Mild Traumatic Brain Injury. PLoS One. 2013 Jun 11;8(6):e66205. PMID: 23776631. PMCID: PMC3679020.
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A significant percentage of individuals diagnosed with mild traumatic brain injury (mTBI) experience persistent post-concussive symptoms (PPCS). Little is known about the pathology of these symptoms and there is often no radiological evidence based on conventional clinical imaging. We aimed to utilize methods to evaluate microstructural tissue changes and to determine whether or not a link with PPCS was present. A novel analysis method was developed to identify abnormalities in high-resolution diffusion tensor imaging (DTI) when the location of brain injury is heterogeneous across subjects. A normative atlas with 145 brain regions of interest (ROI) was built from 47 normal controls. Comparing each subject's diffusion measures to the atlas generated subject-specific profiles of injury. Abnormal ROIs were defined by absolute z-score values above a given threshold. The method was applied to 11 PPCS patients following mTBI and 11 matched controls. Z-score information for each individual was summarized with two location-independent measures: "load" (number of abnormal regions) and "severity" (largest absolute z-score). Group differences were then computed using Wilcoxon rank sum tests. Results showed statistically significantly higher load (p = 0.018) and severity (p = 0.006) for fractional anisotropy (FA) in patients compared with controls. Subject-specific profiles of injury evinced abnormally high FA regions in gray matter (30 occurrences over 11 patients), and abnormally low FA in white matter (3 occurrences over 11 subjects). Subject-specific profiles provide important information regarding the pathology associated with PPCS. Increased gray matter (GM) anisotropy is a novel in-vivo finding, which is consistent with an animal model of brain trauma that associates increased FA in GM with pathologies such as gliosis. In addition, the individualized analysis shows promise for enhancing the clinical care of PPCS patients as it could play a role in the diagnosis of brain injury not revealed using conventional imaging.

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