Diffusion Tensor Imaging of Mild to Moderate Blast-Related Traumatic Brain Injury and Its Sequelae

Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas 77030, USA.
Journal of neurotrauma (Impact Factor: 3.71). 04/2010; 27(4):683-94. DOI: 10.1089/neu.2009.1073
Source: PubMed

ABSTRACT To evaluate the effects of mild to moderate blast-related traumatic brain injury (TBI) on the microstructure of brain white matter (WM) and neurobehavioral outcomes, we studied 37 veterans and service members (mean age 31.5 years, SD = 7.2; post-injury interval 871.5 days; SD = 343.1), whose report of acute neurological status was consistent with sustaining mild to moderate TBI due to blast while serving in Iraq or Afghanistan. Fifteen veterans without a history of TBI or exposure to blast (mean age 31.4 years, SD = 5.4) served as a comparison group, including seven subjects with extracranial injury (post-injury interval 919.5 days, SD = 455.1), and eight who were uninjured. Magnetic resonance imaging disclosed focal lesions in five TBI participants. Post-concussion symptoms (Neurobehavioral Symptom Inventory), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist-Civilian), and global distress and depression (Brief Symptom Inventory) were worse in the TBI participants than the comparison group, but no group differences were found in perceived physical or mental functioning (SF-12). Verbal memory (Selective Reminding) was less efficient in the TBI group, but there were no group differences in nonverbal memory (Selective Reminding) or decision making (Iowa Gambling Task). Verbal memory in the TBI group was unrelated to PTSD severity. Diffusion tensor imaging (DTI) using tractography, standard single-slice region-of-interest measurement, and voxel-based analysis disclosed no group differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC). However, FA of the left and right posterior internal capsule and left corticospinal tract was positively correlated with total words consistently recalled, whereas ADC for the left and right uncinate fasciculi and left posterior internal capsule was negatively correlated with this measure of verbal memory. Correlations of DTI variables with symptom measures were non-significant and inconsistent. Our data do not show WM injury in mild to moderate blast-related TBI in veterans despite their residual symptoms and difficulty in verbal memory. Limitations of the study and implications for future research are also discussed.

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Available from: Elisabeth Wilde, Sep 28, 2015
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    • "However, others have not detected group differences between Service Members and Veterans with and without a reported history of TBI using voxel-based analyses (Davenport et al. 2012; Jorge et al. 2012) or tractography (Levin et al. 2010). Levin et al.'s initial study comparing 37 OIF/OEF Veterans and Service Members with chronic phase mild to moderate blast-related TBI and 15 Veterans without a history of TBI or exposure to blast revealed no differences on DTI-based measures of diffusion (FA and apparent diffusion coefficient or ADC), though DTI measures were related to cognitive performance in some domains (Levin et al. 2010). Jorge et al. used DTI to examine white matter integrity in a relatively larger group (N=72) of Iraq and Afghanistan Veterans with a history of mTBI as compared to a comparison group of deployed Veterans without a history of TBI (N=21) (Jorge et al. 2012). "
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    ABSTRACT: Traumatic brain injury (TBI) remains one of the most prevalent forms of morbidity among Veterans and Service Members, particularly for those engaged in the conflicts in Iraq and Afghanistan. Neuroimaging has been considered a potentially useful diagnostic and prognostic tool across the spectrum of TBI generally, but may have particular importance in military populations where the diagnosis of mild TBI is particularly challenging, given the frequent lack of documentation on the nature of the injuries and mixed etiologies, and highly comorbid with other disorders such as post-traumatic stress disorder, depression, and substance misuse. Imaging has also been employed in attempts to understand better the potential late effects of trauma and to evaluate the effects of promising therapeutic interventions. This review surveys the use of structural and functional neuroimaging techniques utilized in military studies published to date, including the utilization of quantitative fluid attenuated inversion recovery (FLAIR), susceptibility weighted imaging (SWI), volumetric analysis, diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), positron emission tomography (PET), magnetoencephalography (MEG), task-based and resting state functional MRI (fMRI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS). The importance of quality assurance testing in current and future research is also highlighted. Current challenges and limitations of each technique are outlined, and future directions are discussed.
    Brain Imaging and Behavior 09/2015; DOI:10.1007/s11682-015-9444-y · 4.60 Impact Factor
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    • "Whereas Mac Donald et al. (2011) reported that specific regions such as the cerebellum are impacted by blast, others have provided evidence for diffuse abnormalities in white matter not constrained to particular regions (Davenport et al., 2012; Jorge et al., 2012). Still other studies have not found a link between white matter abnormalities and blast-related mTBI using region-of-interest (ROI; Levin et al., 2010) or voxel-based (Bazarian et al., 2013) analyses. Further complicating interpretation of the mTBI literature, several of these studies made group comparisons using non-independent control samples (for discussion, see Watts et al. 2014), potentially biasing their data analyses and inflating the differences between the control and mTBI groups. "
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    ABSTRACT: Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF Veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI-LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function.
    Clinical neuroimaging 04/2015; 28. DOI:10.1016/j.nicl.2015.04.001 · 2.53 Impact Factor
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    • "After experiencing mTBI, soldiers typically return to full duty status immediately after clinical signs begin to disappear, but returning prematurely can increase the risk for repeat injury (MacGregor et al., 2011). Previous studies have shown that mTBI patients experience complications associated with post-concussive syndrome (PCS) (Schneiderman et al., 2008; Belanger et al., 2010; Bryant et al., 2010) or post-traumatic stress disorder (PTSD) (Hoge et al., 2008; Carlson et al., 2010; Levin et al., 2010; Carlson et al., 2011). The underlying mechanisms of these symptoms warrants further investigation and has significant clinical implications (Budde et al., 2011). "
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    ABSTRACT: We induced mild blunt and blast injuries in rats using a custom-built device and utilized in-house diffusion tensor imaging (DTI) software to reconstruct 3-D fiber tracts in brains before and after injury (1, 4, and 7 days). DTI measures such as fiber count, fiber length, and fractional anisotropy (FA) were selected to characterize axonal integrity. In-house image analysis software also showed changes in parameters including the area fraction (AF) and nearest neighbor distance (NND), which corresponded to variations in the microstructure of Hematoxylin and Eosin (H&E) brain sections. Both blunt and blast injuries produced lower fiber counts, but neither injury case significantly changed the fiber length. Compared to controls, blunt injury produced a lower FA, which may correspond to an early onset of diffuse axonal injury (DAI). However, blast injury generated a higher FA compared to controls. This increase in FA has been linked previously to various phenomena including edema, neuroplasticity, and even recovery. Subsequent image analysis revealed that both blunt and blast injuries produced a significantly higher AF and significantly lower NND, which correlated to voids formed by the reduced fluid retention within injured axons. In conclusion, DTI can detect subtle pathophysiological changes in axonal fiber structure after mild blunt and blast trauma. Our injury model and DTI method provide a practical basis for studying mild traumatic brain injury (mTBI) in a controllable manner and for tracking injury progression. Knowledge gained from our approach could lead to enhanced mTBI diagnoses, biofidelic constitutive brain models, and specialized pharmaceutical treatments.
    Journal of Biomechanics 11/2014; 47(15):3704-3711. DOI:10.1016/j.jbiomech.2014.09.026 · 2.75 Impact Factor
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