Detection of Blast-Related Traumatic Brain Injury in U.S. Military Personnel

Abstract

BACKGROUND Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. METHODS We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. RESULTS Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectible intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P = 0.002), and in the right orbitofrontal white matter (P = 0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. CONCLUSIONS DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.)

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

“…Conventional CT and MRI are primarily sensitive to blood from nearby torn capillaries, rather than axonal damage itself, hence they underestimate the presence of DAI, especially in mTBI. New approaches using diffusion tensor imaging (DTI), positron emission topography (PET), and macromelecular proton fraction (MPF) have showed promising capability in detecting injuries and/or abnormalities that are not visible in CT and MRI (e.g., Petrie et al, 2014;MacDonald et al, 2011;Davenport et al, 2012;Shenton et al, 2012).…”

“…Conventional CT and MRI are primarily sensitive to blood from nearby torn capillaries, rather than axonal damage itself, hence they underestimate the presence of DAI, especially in mTBI. New approaches using diffusion tensor imaging (DTI), positron emission topography (PET), and macromelecular proton fraction (MPF) have showed promising capability in detecting injuries and/or abnormalities that are not visible in CT and MRI (e.g., Petrie et al, 2014;MacDonald et al, 2011;Davenport et al, 2012;Shenton et al, 2012).Magnetoencephalogram (MEG) is a non-invasive functional imaging technique that directly measures the magnetic signal due to neuronal activation in gray matter (GM) with high temporal resolution (<1 ms) and spatial localization accuracy (2-3 mm at cortical level) (Leahy et al, 1998). MEG demonstrates sensitivity to abnormal neuronal signals resulting from axonal injuries.…”

Neuropsychological Sequelae of PTSD and TBI Following War Deployment among OEF/OIF Veterans

“…Structural Neuroimaging of TBI-It is well established that conventional structural imaging techniques, such as computed tomography (CT) and MRI, are unlikely to advance our understanding of combat-related mTBI, as these methods are generally considered to lack sufficient sensitivity to detect the subtle abnormalities that characterize mTBI (Mac Donald, et al, 2011). However, studies of civilians have demonstrated the utility of DTI for examining white matter abnormalities in TBI (e.g., Kraus, Susmaras, Caughlin, Walker, Sweeney, & Little, 2007).…”

“…Objective and specific neuroimaging based biomarkers for both disorders would be invaluable for improving diagnosis, subsequent symptom monitoring, and treatment. Additional studies utilizing newer and more advanced imaging technologies will be critical for making such biomarkers a reality (Mac Donald, et al, 2011). Moreover, there is a critical need for studies that use advanced imaging techniques to compare Veterans with PTSD only, TBI only, and co-occurring PTSD-TBI, as such an approach appears essential for disentangling this complex relationship.…”

GFAP-BDP as an Acute Diagnostic Marker in Traumatic Brain Injury: Results from the Prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

“…McCrea et al reported that college football players exhibited cognitive impairment and balance problems after concussion, 12 and although these symptoms resolved, other studies have investigated the effects of repeated insults over time. 13 More recently, in a study of United States military personnel with mild TBI, persistent abnormalities revealed on diffusion tensor imaging (DTI) were consistent with traumatic axonal injury in some subjects, although none had detectable intracranial injury on CT. 14 In a similar study, soldiers with mild TBI were significantly more likely to report poor general health, missed work days, medical visits, and post-concussive symptoms than were soldiers with other injuries, although the effects were confounded by post-traumatic stress disorder (PTSD) and depression. 15 In broader populations of adults with mild TBI, the likelihood of major depressive disorder and epilepsy increased, although effects were also confounded by prior history.…”