Table 3.

Human imaging studies of blast-related TBI.

Imaging modality	Study subjects	Control group	Findings	Reference
Diffusion tensor imaging	Case study of soldier exposed to a large ordinance explosion.	None; abnormal side was compared to contralateral side.	Reduced FA in the left cerebellar hemisphere 7 months after exposure that normalized on follow-up study.	(190)
Diffusion tensor imaging	37 Iraq and Afghanistan veterans studied on average 871.5 days after mild to moderate TBI.	15 Iraq and Afghanistan veterans without blast exposure who sustained injury to other body regions or had no injury.	No between-group differences in FA and apparent diffusion coefficients across white matter regions known to be vulnerable to axonal injury.	(191)
[18F] fluoro-2-deoxyglucose PET (FDG PET)	12 Iraq veterans with at least 1 blast exposure resulting in an mTBI; imaged average of 3.5 years after last exposure.	12 cognitively normal community volunteers without a history of head trauma.	Veterans with blast-related mTBI with or without PTSD showed regional hypometabolism infratentorially (cerebellum, vermis, and pons) and in medial temporal regions.	(192)
Diffusion tensor imaging	63 U.S. military personnel with mTBI evacuated from Iraq or Afghanistan to Landstuhl Germany; all primary blast exposure plus another blast-related mechanism of injury such as struck by blunt object, injured in fall or motor vehicle crash; scanned within 90 days of injury.	21 U.S. military personnel who had blast exposure and other injuries but no clinical diagnosis of TBI.	Reduced FA in veterans with blast-related mTBI in middle cerebellar peduncles, cingulum bundles, and the right orbitofrontal white matter; follow-up scans in 47 subjects 6–12 months later showed persistent abnormalities consistent with evolving injuries.	(193)
Diffusion tensor imaging	25 Iraq and Afghanistan veterans with blast-related mTBI; injuries occurred 2–5 years before imaging.	33 veterans who had not experienced an explosive blast or symptoms of mTBI.	Blast-related mTBI associated with diffuse, global pattern of reduced FA; pattern not affected by history of previous civilian mTBI; with history of more than one blast mTBI trend toward larger number of low FA voxels than with a single blast injury.	(194)
Diffusion tensor imaging	Case report of a marine exposed to multiple primary blasts during a 14-year military career.	A composite fractional-anisotropy template derived from 10 age-matched male veterans without TBI.	Subject had lower FA values in major fiber bundles including the genu, body, and splenium of the corpus callosum and projections that extend bilaterally into the frontal and parietal cortices.	(195)
Diffusion tensor imaging	46 veterans who experienced blast-related mTBI in Iraq and Afghanistan.	None; effects of altered level of consciousness (AOC) vs. loss of consciousness (LOC) and effects of PTSD or major depression examined within subjects.	LOC associated with lower fractional anisotropy (FA) than AOC in 14 regions, including the superior longitudinal fasciculus and corpus callosum; no regions of FA difference between individuals with and without PTSD, or between individuals with and without major depression.	(196)
Diffusion tensor imaging	30 Iraq and Afghanistan veterans who served in combat, and experienced at least one mTBI; imaged approximately 4 years after last tour of duty.	22 Iraq and Afghanistan veterans without a history of TBI.	Blast exposure associated with lower 1st percentile values of FA; lower FA in inferior cerebellar peduncle, fornix, midbrain, and splenium of the corpus callosum before corrections for multiple comparisons.	(93)
High angular resolution diffusion imaging (HARDI)	30 Iraq and Afghanistan veterans with mTBI as well as co-morbid PTSD and depression.	Non-TBI primary (n = 42) and confirmatory (n = 28) control groups from registry of military service members and veterans who served in Iraq and Afghanistan.	Loss of white matter integrity in primary fibers with mTBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including corpus callosum, forceps minor, forceps major, superior and posterior corona radiata, internal capsule, and superior longitudinal fasciculus; loss of white matter integrity correlated with duration of loss of consciousness as well as “feeling dazed or confused” but not with a diagnosis of PTSD or depressive symptoms.	(197)
Task-activated functional MRI (fMRI) (Stop Signal Task)	Iraq and Afghanistan veterans with blast-related mild to moderate TBI (n = 21); civilians with TBI from sports or motor vehicle accidents (n = 21); injuries occurring 1–6 years before enrollment.	Deployed Iraq and Afghanistan veterans who never experienced blast and/or head injury (n = 22); civilians with orthopedic injuries without TBI (n = 23).	Different patterns of activation TBI groups vs. controls; pattern of activation different military vs. civilian TBI.	(198)
Diffusion tensor imaging	4 U.S. military personnel deployed to Iraq with primary blast-related traumatic brain injuries; studied 2–4 years post-exposure.	18 US military personnel deployed to Iraq or Afghanistan with no history of head injury, neurological or psychiatric disorders; studied 6–12 months post-deployment.	DTI scans abnormal in 3 of 4 blast TBI subjects; global comparison of relative anisotropy between blast TBI and controls found decrease in relative anisotropy between groups that was driven entirely by findings in the middle cerebellar peduncle.	(199)
Resting-state functional MRI (fMRI)	13 veterans with blast-induced mTBI and no history of blunt head trauma or PTSD.	50 healthy male subjects with no history of head injuries or substance abuse.	mTBI group exhibited hyperactivity in the temporo-parietal junctions and hypoactivity in the left inferior temporal gyrus; abnormal frequencies in default-mode network, sensorimotor, attentional, and frontal networks; functional connectivity disrupted in six network pairs.	(200)
Resting-state functional MRI (fMRI)	63 U.S. military personnel with concussive blast-related TBI; initial scan within 90 days of injury with a follow-up scan 6– 12 months later in a subset of subjects; second independent cohort of 40 U.S. military personnel with concussive blast-related TBI, initial scan within 30 days post-injury.	21 U.S. military controls having blast exposures but no diagnosis of TBI.	Spatially localized reductions in the participation coefficient, a measure of between-module connectivity, in the TBI patients relative to controls at the time of the initial scan; group differences less prominent on follow-up scans; analysis of the second TBI cohort provided partial replication but no substantial differences on the follow-up scans.	(201)
Diffusion tensor imaging; [18F] fluoro-2-deoxyglucose PET (FDG PET)	34 Iraq and Afghanistan veterans with a history of one or more combined blast/impact-related mTBI.	18 Iraq and Afghanistan veterans without a history of blast/impact-related mTBI.	Subjects with blast/impact-mTBIs exhibited reduced FA in the corpus callosum; reduced macromolecular proton fraction values in subgyral, longitudinal, and cortical/subcortical white matter tracts and gray matter/white matter border regions; reduced cerebral glucose metabolism in parietal, somatosensory, and visual cortices; neuroimaging metrics did not differ between participants with vs. without PTSD.	(202)
Diffusion tensor imaging	23 veterans of the recent military conflicts exposed to primary blast without TBI symptoms; 6 with mTBI due to primary blast.	16 veterans of the recent military conflicts unexposed to blast.	Lower FA and higher radial diffusivity in veterans exposed to primary blast with or without mTBI relative to blast-unexposed veterans; voxel clusters of lower FA spatially dispersed and heterogeneous across affected individuals.	(203)
Magnetic resonance spectroscopy of the hippocampus at 7 T	25 veterans with mTBI due to blast exposure and memory impairment; all at least 1 year post-exposure.	20 controls not further specified.	Hippocampal N-acetyl aspartate to choline and N-acetyl aspartate to creatine ratios decreased in comparison to control subjects.	(204)
Diffusion tensor imaging	37 U.S. service members who sustained TBI (29 mild, 7 moderate, 1 severe; 17 blast and 20 non-blast).	14 non-deployed military controls.	Both blast and non-blast TBI reduced FA in multiple white matter tracts; subcortical superior–inferiorly oriented tracts more vulnerable to blast injury than non-blast injury, while direct impact force more detrimental effects on anterior–posteriorly oriented tracts.	(205)
[18F]-fluoro-2-deoxyglucose positron emission tomography (FDG PET)	14 Iraq and Afghanistan veterans with a history of blast exposure and/or mTBI.	11 veterans with no history of blast exposure or mTBI	Blast exposure and/or mTBI was associated with lower regional metabolic rates of cerebral glucose consumption during wakefulness and rapid eye movement (REM) sleep in the amygdala, hippocampus, parahippocampal gyrus, thalamus, insula, uncus, culmen, visual association cortices, and midline medial frontal cortices.	(206)
Functional MRI (fMRI) during a pain anticipation task	18 male Iraq and Afghanistan veterans with a history of blast-related mTBI related to combat; studied average 4 years after most severe mTBI.	18 healthy male subjects with no reported history of mTBI	Subjects with a history of mTBI showed stronger activations within midbrain periaqueductual gray, right dorsolateral prefrontal cortex, and cuneus during pain anticipation; effects present after controlling for PTSD and depression.	(207)
Structural MRI	12 active duty service members with blast-related mTBI within last 18 months during deployment to Iraq or Afghanistan.	11 demographically matched control service members without TBI scanned within 18 months of deployment.	Blast injury associated with cortical thinning in the left superior temporal and frontal gyri.	(208)