Exploring mesoscale brain connectivity variations and developing sex-specific tractography templates

This study investigates sex-based differences in brain microstructure and establishes sex-specific structural connectomes. Sex variations were analyzed using DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD), along with connectivity strength across 23 regions. Diffusion-weighted MRI data from 1065 healthy adults (490 males, 575 females) were processed using two pipelines. The first developed sex-specific templates using Q-space diffeomorphic reconstruction in DSI-Studio to align orientation distribution functions (ODFs) within sex-specific anatomical spaces. The second pipeline involved subject-wise analysis to investigate sex variations and validate template accuracy. Individual ODFs were reconstructed in subject-specific spaces. A modified FreeSurferSeg atlas was used for segmentation. Fiber tractography was performed using the Euler-tracking algorithm, with connection strength quantified as FA-weighted tract counts between region pairs. The results showed that sex-specific templates provided superior representation of population data, with lower root mean square error compared to cross-/mixed-sex templates. Significant sex differences were observed: females exhibited higher FA in 70 % of regions (p < 0.05), while males showed higher MD and RD in 91 % and 96 % of regions, respectively. Connectivity analysis revealed stronger connections in females for 70 % of region pairs, particularly between the corpus callosum and cerebral cortex/white matter. These findings confirm the need for sex-specific templates for accurate neuroimaging analysis. The observed microstructural patterns, such as higher FA/connectivity in females and greater diffusivity in males, indicate that biological factors contribute to sex-based differences in neurological conditions. For instance, incorporating these templates into biomechanical models could enhance research on traumatic brain injury.