Development of white matter fibre density and morphology over childhood: A longitudinal fixel-based analysis

Abstract

Using a novel longitudinal fixel-based analysis framework, we demonstrate that white matter fibre density and fibre cross-section increased within a 16-month scan rescan period in specific regions. The observed increases might reflect increasing axonal diameter or axon count. Pubertal stage or progression did not influence the rate of fibre development in the early stages of puberty. Future work should focus on quantifying these measures across a wider age range to capture the full spectrum of fibre development across the pubertal period.

Early childhood development of white matter fiber density and morphology

“…However, our FD findings are less widespread than we hypothesized: we report no significant FD increases in the genu of the corpus callosum, fornix, inferior longitudinal fasciculi, superior longitudinal fasciculi, or uncinate fasciculi. Although we find less widespread FD changes, some are larger in magnitude than that reported in older children (3.1-7.1% as compared to 2.5-3.5% reported by (Genc et al, 2018b)). Together, these findings suggest that axonal density changes during early childhood may be characterized by profound increases in select tracts (e.g.…”

“…Here we see similar regional trends to those of NDI studies, with faster FD increases in the corticospinal tract and splenium of the corpus callosum (Chang et al, 2015;Jelescu et al, 2015) and high relative changes in the cingulum bundles and arcuate fasciculi (Mah et al, 2017). Our findings are also consistent with longitudinal FBA analyses in older children (aged 9-13), showing FD increases with age in several WM tracts, including the corpus callosum, cingulum bundles, superior longitudinal fasciculi, inferior frontal-occipital fasciculi and corticospinal tracts (Genc et al, 2018b(Genc et al, , 2019. However, our FD findings are less widespread than we hypothesized: we report no significant FD increases in the genu of the corpus callosum, fornix, inferior longitudinal fasciculi, superior longitudinal fasciculi, or uncinate fasciculi.…”

“…A recent large sample study in children ages 2-8 years provides evidence in support of this pattern, showing that changes in diffusion tensor metrics (FA and MD) across early childhood are more rapid in posterior regions as compared to frontal-temporal tracts (Reynolds et al, 2019). This spatial trend is also supported by FBA (Genc et al, 2018b) and NODDI (Mah et al, 2017) studies showing that axonal density/packing changes during late childhood are greatest in the forceps major, a posterior commissural fiber. These findings suggest that developmental changes in axonal density may follow a similar spatial pattern to changes observed in DTI metrics.…”

“…Studies utilizing FBA in a neurodevelopmental context suggest white matter development from late childhood to early adulthood may be driven by increases in both axonal packing/density and fiber bundle size (Genc et al, 2017b(Genc et al, , 2018b(Genc et al, , 2018a(Genc et al, , 2019. Age-related increases in axonal packing/density from late childhood to adulthood have also been suggested by studies utilizing an alternative diffusion model, "neurite orientation and dispersion density imaging (NODDI)" (Chang et al, 2015;Genc et al, 2017a;Mah et al, 2017); these changes have been shown to occur alongside increasing FA and decreasing MD during late childhood to adulthood and correlate more strongly with age than DTI metrics (Genc et al, 2017a;Mah et al, 2017).…”

“…To compare our FBA metric findings to more commonly used DTI metrics, we also assessed changes in FA and MD, as well as radial diffusivity (RD) and axial diffusivity (AD). Considering previous literature suggestive of widespread developmental increases in axonal packing and fiber bundle size from late childhood to adulthood (Chang et al, 2015;Genc et al, 2018aGenc et al, , 2018bGenc et al, , 2017aMah et al, 2017), we hypothesized that FD, FC, and FDC would all increase with age throughout the whole brain (but particularly in major white matter tracts), indicative of ubiquitous axonal density and cross-sectional fiber bundle growth during early childhood. Furthermore, considering evidence for varying rates of maturation across white matter regions (Dubois et al, 2014;Lebel et al, 2012;Reynolds et al, 2019;Westlye et al, 2010), we hypothesized that FD, FC and FDC changes would be most rapid in commissural and projection fibers, and slowest in frontal-temporal tracts.…”