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Structural substrates of sex differences in human function and behavior have been elucidated in previous studies. Diffusion weighted magnetic resonance imaging (DW-MRI) is a widely used non-invasive imaging technique in studying human brain white matter structural organization. While many DW-MRI studies reporting sex differences in WM structure are based on diffusion tensor imaging (DTI) measures, tract specific microstructural differences require further investigation. In this study, we aim to investigate sex differences and sex-specific hemispheric differences in white matter microstructural development in healthy 8-year-old children based on novel track weighted imaging (TWI) analysis. Average pathlength map (APM) is a TWI contrast in which the average length of fibers passing through a voxel is utilized. In this study, we employed tract specific APM measures to evaluate sex differences in WM microstructural development. A total of 37 WM tracts were analyzed including 7 commissural tracts, 9 bilateral association tracts and 6 bilateral projection tracts. APM maps were generated for each tract. Tract-wise group tests were done using the mean values of APM maps. Sex differences were tested using general linear model based group comparisons. Age and total brain volume were included as covariates in the group analysis. Sex specific hemispheric differences were performed for the 15 bilateral tracts. One sample t-tests were done independently for left<right and right<left cases and the APM measures were controlled for age and total cerebral hemispheric volume. P-values<0.05 were considered significant after correcting for multiple comparisons accounting for the total number of tracts. Significant sex differences were revealed in APM measures between boys and girls in 11 WM tracts including rostral body of corpus callosum (CC), left inferior fronto-occipital fasciculus (IFOF), right cingulum, bilateral first and second segments of superior longitudinal fasciculus (SLF), right middle longitudinal fasciculus (MLF), bilateral fronto-pontine (FPT) and right parieto-occipital pontine tracts (POPT). The sex differences showed higher APM values for these 11 tracts in boys as compared to that of girls. In hemispheric differences analysis for both boys and girls, 2 tracts, arcuate fasciculus and optic radiation showed higher APM in left tracts as compared right; 5 tracts, IFOF, MLF, third segment of SLF, FPT and superior thalamic radiation showed higher APM in right tracts as compared to left. This indicates that boys and girls possess similar lateral asymmetries in these 7 tracts. Additionally, anterior thalamic radiation (ATR) showed higher APM in left tract and 4 tracts, first segment of SLF, POPT, inferior longitudinal fasciculus and cortico-spinal tract showed higher APM in right for boys. In girls, second segment of SLF and uncinate fasciculus showed higher APM in right hemisphere. These results indicate different lateral asymmetries between boys and girls for 7 tracts. Overall, boys showed higher average fiber length in most of the tracts, even after controlling for total brain volume.
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