A multiparametric analysis of white matter maturation during late childhood and adolescence.

White matter development has been well described using diffusion tensor imaging (DTI), but the microstructural processes driving development remain unclear due to methodological limitations. Here, using neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT), and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT), we describe white matter development at the microstructural level in a longitudinal cohort of healthy 6-15 year olds. We evaluated age and gender-related trends in fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), orientation dispersion index (ODI), quantitative ihMT (qihMT), myelin volume fraction (VFm ), and g-ratio. We found age-related increases of VFm in most regions, showing ongoing myelination in vivo during late childhood and adolescence for the first time. No relationship was observed between qihMT and age, suggesting myelin volume increases are driven by increased water content. Age-related increases were observed for NDI, suggesting axonal packing is also occurring during this time. g-ratio decreased with age in the uncinate fasciculus, implying changes in communication efficiency are ongoing in this region. FA increased and MD decreased with age in most regions. Gender effects were present in the left cingulum for FA, and an age-by-gender interaction was found for MD in the left uncinate fasciculus. These findings suggest that FA and MD remain useful markers of gender-related processes, and gender differences are likely driven by factors other than myelin. We conclude that white matter development during late childhood and adolescence is driven by a combination of axonal packing and myelin volume increases.