Genetic and environmental influences of variation in diffusion MRI measures of white matter microstructure

Quantitative neuroimaging studies in twin samples can investigate genetic contributions to brain structure and microstructure. Diffusion tensor imaging (DTI) studies with twin samples have shown moderate to high heritability in white matter microstructure. This study investigates the genetic and environmental contributions of another widely used diffusion MRI model not yet applied to twin studies, neurite orientation dispersion and density imaging (NODDI). The NODDI model is a multicompartment model of the diffusion-weighted MRI signal, providing estimates of neurite density (ND) and the orientation dispersion index (ODI). A cohort of monozygotic (MZ) and same-sex dizygotic (DZ) twins (N = 460 individuals) between 13 and 24 years of age were scanned with a multi-shell diffusion weighted imaging protocol. Select white matter (WM) regions of interest (ROI) were extracted. Biometric structural equation modeling estimated the relative contributions from additive genetic (A) and common (C) and unique environmental (E) factors. Genetic factors for the NODDI measures accounted for 91% and 65% of the variation of global ND and ODI, respectively, compared with 83% for FA. We observed higher heritability for ND than both FA and ODI in 25 of 30 discrete white matter regions that we examined, suggesting ND may be more sensitive to underlying genetic sources of variation. This study demonstrated that genetic factors play a key role in the development of white matter microstructure using both DTI and NODDI.