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Sex differences in brain structure significantly influence traumatic brain injury (TBI) onset and progression, yet this area is understudied. Herein, we developed sex-specific brain anatomical (macroscale) and axonal tract (mesoscale) templates and explored the sex variations at subject level using a set of T1-MRI (609 males, 721 females) and DTI images (506 males, 594 females). The FreeSurfer, ANTs, and DSI-Studio packages were used. We investigated overall/regional volumes, DTI metrics (including fractional anisotropy (FA), mean diffusivity, and radial diffusivity), and connectivity matrix across 23 brain regions. The brain connectome was derived by multiplying the fiber tract counts and the FA values within the connecting tracts, quantifying the connection strength within each pair of regions. Our subject-wise analysis revealed significant sex based differences (Mann-Whitney p-values < 0.05) across most studied regions for all parameters. The largest sex differences in brain connections were observed in five regions: corpus callosum and right/left cortex and cerebral white matter, all stronger in females. Brain regions were typically larger in males, yet females had higher fractional volumes in the majority of regions except for CSF and ventricles, known for their cushioning effect during head impacts. Additionally, the sex-specific templates better represented their targeted sex compared to opposite or mixed-sex populations as evaluated by root-mean-square-errors when comparing the DTI metrics and connectivity from the DTI templates against the median of subjects and deformation field in registering the subjects to the T1-MRI templates. Our findings highlight the necessity of sex-specific templates in accurate brain modeling and TBI research.
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Tractography Study of the Human Brain: Sex Specific Templates and Sex Variations
The human brain is sexually dimorphic and these sex differences have shown to affect brain response to trauma. We investigated the sex differences in the tract structures by studying diffusion weighted (DW) images of 594 females and 506 males from the Human-Connectome-Project dataset. All the female and male DW images were reconstructed in the ICBM152 space using Q-Space diffeomorphic reconstruction technique and their mapped orientation distribution function images were averaged to generate the female- and male-DW-templates. The tract streamlines were generated through tractography for female and male templates and normalized to the total brain volume . The distributions of normalized tract lengths were significantly different between female- and male-templates and the female-template showed to have more longer normalized tracts compared to the male template. For the regional analysis, the templates were parcellated into sixteen regions of interests (ROI) including brain-stem, five subregions of corpus-callosum, and right and left hippocampus, thalamus, cerebellum white-matter (WM), cerebral WM, and cerebellum cortex using a FreeSurfer-based segmentation atlas. For all the ROIs, the average fractional anisotropy (0.5-5.7%) and normalized tract lengths (1.1-2.7%) were larger in female template while the average mean diffusion was larger (1.3-5.6%) in male-template. Quantifying brain connectivity by counting number of tracts passing through pairs of ROIs, showed more pairs with a higher connectivity in female-template, and one of the highest percentages of sex differences in right/left cerebellum WM/cortex connections. Our results reinforce the need to continue investigating the sex variations in axonal structure and their effects to brain trauma.
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- Award ID(s):
- 2138719
- PAR ID:
- 10620659
- Publisher / Repository:
- Mary Ann Liebert, Inc.
- Date Published:
- Journal Name:
- Journal of Neurotrauma
- Volume:
- 40
- Issue:
- 15-16
- ISSN:
- 0897-7151
- Page Range / eLocation ID:
- A-66
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1089/neu.2023.29130.abstracts
