Compromised Neurocircuitry in Chronic Blast-Related Mild Traumatic Brain Injury.

The aim of this study was to apply recently developed automated fiber segmentation and quantification methods using diffusion tensor imaging (DTI) and DTI-based deterministic and probabilistic tractography to access local and global diffusion changes in blast-induced mild traumatic brain injury (bmTBI). Two hundred and two (202) male active US service members who reported persistent post-concussion symptoms for more than 6 months after injury were recruited. An additional forty (40) male military controls were included for comparison. DTI results were examined in relation to post-concussion and post-traumatic stress disorder (PTSD) symptoms. No significant group difference in DTI metrics was found using voxel-wise analysis. However, group comparison using tract profile analysis and tract specific analysis, as well as single subject analysis using tract profile analysis revealed the most prominent white matter microstructural injury in chronic bmTBI patients over the frontal fiber tracts, that is, the front-limbic projection fibers (cingulum bundle, uncinate fasciculus), the fronto-parieto-temporal association fibers (superior longitudinal fasciculus), and the fronto-striatal pathways (anterior thalamic radiation). Effects were noted to be sensitive to the number of previous blast exposures, with a negative association between fractional anisotropy (FA) and time since most severe blast exposure in a subset of the multiple blast-exposed group. However, these patterns were not observed in the subgroups classified using macrostructural changes (T2 white matter hyperintensities). Moreover, post-concussion symptoms and PTSD symptoms, as well as neuropsychological function were associated with low FA in the major nodes of compromised neurocircuitry. Hum Brain Mapp 38:352-369, 2017. © 2016 Wiley Periodicals, Inc.

Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury.

PURPOSE: To detect cerebral microhemorrhages in military service members with chronic traumatic brain injury by using susceptibility-weighted magnetic resonance (MR) imaging. The longitudinal evolution of microhemorrhages was monitored in a subset of patients by using quantitative susceptibility mapping. MATERIALS AND METHODS: The study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants underwent two-dimensional conventional gradient-recalled-echo MR imaging and three-dimensional flow-compensated multiecho gradient-recalled-echo MR imaging (processed to generate susceptibility-weighted images and quantitative susceptibility maps), and a subset of patients underwent follow-up imaging. Microhemorrhages were identified by two radiologists independently. Comparisons of microhemorrhage number, size, and magnetic susceptibility derived from quantitative susceptibility maps between baseline and follow-up imaging examinations were performed by using the paired t test. RESULTS: Among the 603 patients, cerebral microhemorrhages were identified in 43 patients, with six excluded for further analysis owing to artifacts. Seventy-seven percent (451 of 585) of the microhemorrhages on susceptibility-weighted images had a more conspicuous appearance than on gradient-recalled-echo images. Thirteen of the 37 patients underwent follow-up imaging examinations. In these patients, a smaller number of microhemorrhages were identified at follow-up imaging compared with baseline on quantitative susceptibility maps (mean ± standard deviation, 9.8 microhemorrhages ± 12.8 vs 13.7 microhemorrhages ± 16.6; P = .019). Quantitative susceptibility mapping-derived quantitative measures of microhemorrhages also decreased over time: -0.85 mm(3) per day ± 1.59 for total volume (P = .039) and -0.10 parts per billion per day ± 0.14 for mean magnetic susceptibility (P = .016). CONCLUSION: The number of microhemorrhages and quantitative susceptibility mapping-derived quantitative measures of microhemorrhages all decreased over time, suggesting that hemosiderin products undergo continued, subtle evolution in the chronic stage.

Findings from Structural MR Imaging in Military Traumatic Brain Injury.

PURPOSE: To describe the initial neuroradiology findings in a cohort of military service members with primarily chronic mild traumatic brain injury (TBI) from blast by using an integrated magnetic resonance (MR) imaging protocol. MATERIALS AND METHODS: This study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI (not explicitly age- and sex-matched). MR examinations were performed at 3 T primarily with three-dimensional volume imaging at smaller than 1 mm(3) voxels for the structural portion of the examination. The structural portion of this examination, including T1-weighted, T2-weighted, before and after contrast agent administrtion T2 fluid attenuation inversion recovery, and susceptibility-weighted images, was evaluated by neuroradiologists by using a modified version of the neuroradiology TBI common data elements (CDEs). Incident odds ratios (ORs) between the TBI participants and a comparison group without TBI were calculated. RESULTS: The 834 participants were diagnosed with predominantly chronic (mean, 1381 days; median, 888 days after injury) and mild (92% [768 of 834]) TBI. Of these participants, 84.2% (688 of 817) reported one or more blast-related incident and 63.0% (515 of 817) reported loss of consciousness at the time of injury. The presence of white matter T2-weighted hyperintense areas was the most common pathologic finding, observed in 51.8% (432 of 834; OR, 1.75) of TBI participants. Cerebral microhemorrhages were observed in a small percentage of participants (7.2% [60 of 834]; OR, 6.64) and showed increased incidence with TBI severity (P < .001, moderate and severe vs mild). T2-weighted hyperintense areas and microhemorrhages did not collocate by visual inspection. Pituitary abnormalities were identified in a large proportion (29.0% [242 of 834]; OR, 16.8) of TBI participants. CONCLUSION: Blast-related injury and loss of consciousness is common in military TBI. Structural MR imaging demonstrates a high incidence of white matter T2-weighted hyperintense areas and pituitary abnormalities, with a low incidence of microhemorrhage in the chronic phase.

Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy.

Optimal four-dimensional imaging requires high spatial resolution in all dimensions, high speed and minimal photobleaching and damage. We developed a dual-view, plane illumination microscope with improved spatiotemporal resolution by switching illumination and detection between two perpendicular objectives in an alternating duty cycle. Computationally fusing the resulting volumetric views provides an isotropic resolution of 330 nm. As the sample is stationary and only two views are required, we achieve an imaging speed of 200 images/s (i.e., 0.5 s for a 50-plane volume). Unlike spinning-disk confocal or Bessel beam methods, which illuminate the sample outside the focal plane, we maintain high spatiotemporal resolution over hundreds of volumes with negligible photobleaching. To illustrate the ability of our method to study biological systems that require high-speed volumetric visualization and/or low photobleaching, we describe microtubule tracking in live cells, nuclear imaging over 14 h during nematode embryogenesis and imaging of neural wiring during Caenorhabditis elegans brain development over 5 h.