Gestational age-specific DTI templates of the neonatal brain: Application in preterm developmental study

Due to significant differences in brain volume, morphology, and white matter integrity among neonates of varying gestational ages, using a single full-term template for preterm analysis inevitably introduces analytical errors. To address this, we aimed to develop gestational-age-specific stereotaxic DTI templates using retrospective diffusion MRI scans from 161 neonates acquired between August 2021 and January 2024. The cohort was stratified into four WHO-defined subgroups: extremely preterm (n = 31), very preterm (n = 29), moderate to late preterm (n = 28), and full-term (n = 73). Templates were constructed via iterative registration, with corresponding atlases transformed from JHU space and manually corrected. Quantitative evaluation using the Jacobian determinant and standard deviation revealed that our age-specific templates demonstrated significantly lower deformation magnitude and registration error compared to a standard full-term template. When applied to investigate developmental differences, we observed progressively more extensive fractional anisotropy reductions from moderate-to-late to extremely preterm neonates. Notably, commissural fibers, particularly the corpus callosum body (0.194 ± 0.005 in extremely preterm vs. 0.230 ± 0.003 in full-term, p < 0.001), exhibited significant developmental gradients. Consequently, these constructed gestational-age-specific DTI templates offer a robust tool to improve the accuracy of morbidity risk predictions and facilitate multicenter studies of preterm neonates.