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Volumetric and shape analyses of subcortical structures in United States service members with mild traumatic brain injury

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Abstract

Mild traumatic brain injury (mTBI) is a significant health concern. The majority who sustain mTBI recover, although ~20 % continue to experience symptoms that can interfere with quality of life. Accordingly, there is a critical need to improve diagnosis, prognostic accuracy, and monitoring (recovery trajectory over time) of mTBI. Volumetric magnetic resonance imaging (MRI) has been successfully utilized to examine TBI. One promising improvement over standard volumetric approaches is to analyze high-dimensional shape characteristics of brain structures. In this study, subcortical shape and volume in 76 Service Members with mTBI was compared to 59 Service Members with orthopedic injury (OI) and 17 with post-traumatic stress disorder (PTSD) only. FreeSurfer was used to quantify structures from T1-weighted 3 T MRI data. Radial distance (RD) and Jacobian determinant (JD) were defined vertex-wise on parametric mesh-representations of subcortical structures. Linear regression was used to model associations between morphometry (volume and shape), TBI status, and time since injury (TSI) correcting for age, sex, intracranial volume, and level of education. Volumetric data was not significantly different between the groups. JD was significantly increased in the accumbens and caudate and significantly reduced in the thalamus of mTBI participants. Additional significant associations were noted between RD of the amygdala and TSI. Positive trend-level associations between TSI and the amygdala and accumbens were observed, while a negative association was observed for third ventricle. Our findings may aid in the initial diagnosis of mTBI, provide biological targets for functional examination, and elucidate regions that may continue remodeling after injury.

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Acknowledgments

The view(s) expressed herein are those of the author and do not reflect the official policy or position of the Defense and Veterans Brain Injury Center, Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, Department of Defense, or the U.S. Government. We gratefully acknowledge the generous time and effort that the Service Members made in supporting this study. We also gratefully acknowledge the clinical effort and expertise of the Brooke Army Medical Center Brain Injury and Rehabilitation Service staff in the identification, recruitment, consenting, and treatment of Service Members who are a part of this study. This work is supported in part by the Defense and Veterans Brain Injury Centers, the Telemedicine and Advanced Technology Research Center (TATRC) at the U.S. Army Medical Research and Materiel Command (USAMRMC; W81XWH-13-2-0025), the Chronic Effects of Neurotrauma Consortium (CENC; PT108802-SC104835), the National Institutes of Health (NIH U54 EB020403), and the Veterans Administration (VA Merit Grant).

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Correspondence to David F. Tate.

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This research was approved and monitored by the local hospital IRB (protocol #3743378) and Human Research Protection Office (HRPO) at the US Army Medical Department Medical Research and Materiel Command (USAMRMC) (protocol #A-17660). Study procedures were thus in compliance with ethical standards as laid down by the 1964 Declaration of Helsinki.

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415_2016_8236_MOESM1_ESM.tiff

Supplementary material 1 (TIFF 385 kb) Supplemental Fig. 1. Scatterplots of the associations between TSI and subcortical structure volumes. Structures are separated column wise by left hemisphere structures, midline structures and right hemisphere structures from left to right columns

415_2016_8236_MOESM2_ESM.tiff

Supplementary material 2 (TIFF 6019 kb) Supplemental Fig. 1. Scatterplots of the associations between TSI and subcortical structure volumes. Structures are separated column wise by left hemisphere structures, midline structures and right hemisphere structures from left to right columns

415_2016_8236_MOESM3_ESM.docx

Supplementary material 3 (DOCX 115 kb) Supplementary Table 1. Number of vertices comprising subcortical surfaces. Supplemental Table 2. Volumetric statistical associations between TBI and Orthopedic Injured only controls before and after FDR correction. Supplemental Table 3. This table shows the significant volumetric results between mTBI and OI only controls before and after FDR correction. Supplementary Table 4. Preliminary results showing the clinical variables that were noted to be significant before FDR correction in the shape analyses. The number of vertices, the t value, and the effect size are shown

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Tate, D.F., Wade, B.S.C., Velez, C.S. et al. Volumetric and shape analyses of subcortical structures in United States service members with mild traumatic brain injury. J Neurol 263, 2065–2079 (2016). https://doi.org/10.1007/s00415-016-8236-7

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