White matter microstructural abnormalities in blast-exposed combat veterans: accounting for potential pre-injury factors using consanguineous controls

Andrew C. McClelland, Roman Fleysher, Weiya Mu, Namhee Kim, Michael L. Lipton

Research output: Contribution to journalArticle

Abstract

Purpose: Assess the prevalence of white matter microstructural changes in combat veterans, within the context of a highly matched control group comprising unexposed close relatives. Methods: This prospective study had institutional review board approval, included written informed consent, and is HIPAA-compliant. Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18 unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous relationship to a member of the subject group. Whole-brain voxel-based comparison of fractional anisotropy (FA) was performed using both group and individual analyses. Areas where effects on FA were detected were subsequently characterized by extracting radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) from the regions of abnormal FA. Results: Controls did not differ from veterans on any background demographic factor. In voxel-based group comparison, we identify high fractional anisotropy (FA) in veterans compared to controls (p < 0.01). Within individual veterans, we find multiple areas of both abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent with multifocal traumatic axonal injury. In individualized analyses, low FA areas demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in both group and individual analyses. Conclusions: Combat-related blast exposure is associated with microstructural white matter abnormalities, and the nature of the control group decreases the likelihood that the findings reflect underlying background differences. Abnormalities are heterogeneously distributed across patients, consistent with TAI, and include areas of low and high FA.

Original languageEnglish (US)
JournalNeuroradiology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Anisotropy
Veterans
Wounds and Injuries
2003-2011 Iraq War
Afghan Campaign 2001-
Health Insurance Portability and Accountability Act
Control Groups
Diffusion Tensor Imaging
White Matter
Research Ethics Committees
Informed Consent
Research Design
Demography
Prospective Studies
Brain

Keywords

  • Blast exposure
  • Diffusion tensor imaging (DTI)
  • Mild traumatic brain injury (mTBI)

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{41bf7cb5acb74c84a7f6a52f43c9a3ce,
title = "White matter microstructural abnormalities in blast-exposed combat veterans: accounting for potential pre-injury factors using consanguineous controls",
abstract = "Purpose: Assess the prevalence of white matter microstructural changes in combat veterans, within the context of a highly matched control group comprising unexposed close relatives. Methods: This prospective study had institutional review board approval, included written informed consent, and is HIPAA-compliant. Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18 unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous relationship to a member of the subject group. Whole-brain voxel-based comparison of fractional anisotropy (FA) was performed using both group and individual analyses. Areas where effects on FA were detected were subsequently characterized by extracting radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) from the regions of abnormal FA. Results: Controls did not differ from veterans on any background demographic factor. In voxel-based group comparison, we identify high fractional anisotropy (FA) in veterans compared to controls (p < 0.01). Within individual veterans, we find multiple areas of both abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent with multifocal traumatic axonal injury. In individualized analyses, low FA areas demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in both group and individual analyses. Conclusions: Combat-related blast exposure is associated with microstructural white matter abnormalities, and the nature of the control group decreases the likelihood that the findings reflect underlying background differences. Abnormalities are heterogeneously distributed across patients, consistent with TAI, and include areas of low and high FA.",
keywords = "Blast exposure, Diffusion tensor imaging (DTI), Mild traumatic brain injury (mTBI)",
author = "McClelland, {Andrew C.} and Roman Fleysher and Weiya Mu and Namhee Kim and Lipton, {Michael L.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00234-018-2070-9",
language = "English (US)",
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T1 - White matter microstructural abnormalities in blast-exposed combat veterans

T2 - accounting for potential pre-injury factors using consanguineous controls

AU - McClelland, Andrew C.

AU - Fleysher, Roman

AU - Mu, Weiya

AU - Kim, Namhee

AU - Lipton, Michael L.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: Assess the prevalence of white matter microstructural changes in combat veterans, within the context of a highly matched control group comprising unexposed close relatives. Methods: This prospective study had institutional review board approval, included written informed consent, and is HIPAA-compliant. Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18 unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous relationship to a member of the subject group. Whole-brain voxel-based comparison of fractional anisotropy (FA) was performed using both group and individual analyses. Areas where effects on FA were detected were subsequently characterized by extracting radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) from the regions of abnormal FA. Results: Controls did not differ from veterans on any background demographic factor. In voxel-based group comparison, we identify high fractional anisotropy (FA) in veterans compared to controls (p < 0.01). Within individual veterans, we find multiple areas of both abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent with multifocal traumatic axonal injury. In individualized analyses, low FA areas demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in both group and individual analyses. Conclusions: Combat-related blast exposure is associated with microstructural white matter abnormalities, and the nature of the control group decreases the likelihood that the findings reflect underlying background differences. Abnormalities are heterogeneously distributed across patients, consistent with TAI, and include areas of low and high FA.

AB - Purpose: Assess the prevalence of white matter microstructural changes in combat veterans, within the context of a highly matched control group comprising unexposed close relatives. Methods: This prospective study had institutional review board approval, included written informed consent, and is HIPAA-compliant. Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18 unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous relationship to a member of the subject group. Whole-brain voxel-based comparison of fractional anisotropy (FA) was performed using both group and individual analyses. Areas where effects on FA were detected were subsequently characterized by extracting radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) from the regions of abnormal FA. Results: Controls did not differ from veterans on any background demographic factor. In voxel-based group comparison, we identify high fractional anisotropy (FA) in veterans compared to controls (p < 0.01). Within individual veterans, we find multiple areas of both abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent with multifocal traumatic axonal injury. In individualized analyses, low FA areas demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in both group and individual analyses. Conclusions: Combat-related blast exposure is associated with microstructural white matter abnormalities, and the nature of the control group decreases the likelihood that the findings reflect underlying background differences. Abnormalities are heterogeneously distributed across patients, consistent with TAI, and include areas of low and high FA.

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