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

Abstract

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.

Multimodal principal component analysis to identify major features of white matter structure and links to reading

“…Age-related trends tended to be similar between left and right hemispheres, suggesting that at the macro-scale, brain development is similar between hemispheres. This is in contrast to investigations of individual microstructural features, where increases in VF m were shown to be largely left-lateralized during adolescence [57]. PC2 findings may be driven by NDI, as NDI has been previously shown to be age-sensitive and increases bilaterally throughout adolescence [57][58][59].…”

“…This is in contrast to investigations of individual microstructural features, where increases in VF m were shown to be largely left-lateralized during adolescence [57]. PC2 findings may be driven by NDI, as NDI has been previously shown to be age-sensitive and increases bilaterally throughout adolescence [57][58][59]. One relationship between PC1 and age remained in the left arcuate following multiple comparisons.…”

White matter tract myelin maturation and its association with general psychopathology in adolescence and early adulthood

“…However, MT measures may also be sensitive to the effects of neuroinflammation or oedema (Gareau, Rutt, Karlik, & Mitchell, ; Stanisz, Webb, Munro, Pun, & Midha, ) and as such remain an imperfect measure of myelin. Future research might usefully address the specificity of our longitudinal findings to myelination by comparing MT saturation effects with other white matter microstructure metrics, an approach adopted in recent work in studies of late childhood and early adolescence, albeit reports on cross‐sectional and not longitudinal data (Geeraert, Lebel, & Lebel, ; Moura et al, ).…”

<p>Neurite orientation and dispersion density imaging: clinical utility, efficacy, and role in therapy</p>

“…62 Age-related increases of ND were also reported during late childhood and adolescence, suggesting axonal packing in this term. 63 For adults, Nazeri and colleagues 64 revealed age-related OD decreases in frontoparietal regions and increases in the hippocampus, as well as a relationship with executive function. Ota et al 65 also reported age-related changes in healthy adults in terms of NODDI and DTI/DKI parameters.…”