Detailing neuroanatomical development in late childhood and early adolescence using NODDI

Abstract

Diffusion tensor imaging (DTI) studies have provided much evidence of white and subcortical gray matter changes during late childhood and early adolescence that suggest increasing myelination, axon density, and/or fiber coherence. Neurite orientation dispersion and density imaging (NODDI) can be used to further characterize development in white and subcortical grey matter regions in the brain by improving specificity of the MRI signal compared to conventional DTI. We used measures from NODDI and DTI to examine white and subcortical gray matter development in a group of 27 healthy participants aged 8–13 years. Neurite density index (NDI) was strongly correlated with age in nearly all regions, and was more strongly associated with age than fractional anisotropy (FA). No significant correlations were observed between orientation dispersion index (ODI) and age. This suggests that white matter and subcortical gray matter changes during late childhood and adolescence are dominated by changes in neurite density (i.e., axon density and myelination), rather than increasing coherence of axons. Within brain regions, FA was correlated with both ODI and NDI while mean diffusivity was only related to neurite density, providing further information about the structural variation across individuals. Data-driven clustering of the NODDI parameters showed that microstructural profiles varied along layers of white matter, but that that much of the white and subcortical gray matter matured in a similar manner. Clustering highlighted isolated brain regions with decreasing NDI values that were not apparent in region-of-interest analysis. Overall, these results help to more specifically understand patterns of white and gray matter development during late childhood and early adolescence.

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

“…NODDI measures help to clarify trends in DTI measures, and have been leveraged by previous cross‐sectional studies to describe age‐related trends in white matter with greater specificity. Our longitudinal results are in line with previous cross‐sectional findings of positive correlations between NDI and age and no correlation with ODI during adolescence (Chang et al, ; Genc, Malpas, et al, ; Mah et al, ). While most regions and measures showed linear trends, quadratic models outperformed linear models for MD in the splenium, and NDI in all regions except the right IFOF, right CST, and splenium, however, quadratic age effects did not survive multiple comparisons.…”

“…While some of these measures have been applied in studies of white matter development, major knowledge gaps remain unexplored. Cross‐sectional studies have applied NODDI to show NDI is more sensitive to age‐related change than FA or MD (Genc, Malpas, Holland, Beare, & Silk, ), and increases during late childhood and adolescence (Chang et al, ; Genc, Malpas, et al, ; Mah, Geeraert, & Lebel, ). On the other hand, ODI undergoes little to no change during childhood and adolescence, suggesting fiber coherence is established early and remains stable during childhood.…”

A review of diffusion MRI of typical white matter development from early childhood to young adulthood

“…164 Another NODDI study of 27 children aged 8-13 years showed positive NDI-age correlations in all tracts, and no ODI-age correlations. 81 Together, these suggest increasing myelin and/or axonal packing, but negligible changes in axon coherence during development. Finally, a NODDI study of 72 children and adolescents aged 4-19 years demonstrated that NDI is more strongly correlated with age than FA in healthy adolescents, suggesting that it is a better measure of age-related change.…”

“…A NODDI study in 66 healthy subjects from 7 to 63 years showed a logarithmic growth pattern of neurite density index (NDI) and an exponential growth pattern of the neurite orientation dispersion index (ODI); between 7 and 20 years, the ODI was flat, whereas NDI increased, coinciding with known increases of FA . Another NODDI study of 27 children aged 8–13 years showed positive NDI‐age correlations in all tracts, and no ODI‐age correlations . Together, these suggest increasing myelin and/or axonal packing, but negligible changes in axon coherence during development.…”

Early childhood development of white matter fiber density and morphology

“…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). Taken together, these findings suggest that increasing axonal density/packing and fiber bundle size underlie the DTI changes observed in late-childhood to adulthood, though whether this is the case in early childhood remains unclear.…”