Quantification of apparent axon density and orientation dispersion in the white matter of youth born with congenital heart disease

Background: White matter alterations have previously been demonstrated in adolescents born with congenital heart disease (CHD) using diffusion tensor imaging (DTI). However, due to the non-specific nature of DTI metrics, it is difficult to interpret these findings in terms of their microstructural implications. This study investigated the use of neurite orientation dispersion and density imaging (NODDI), which involves the acquisition of advanced multiple b-value data over two shells and provides proxy measures of apparent axon density and orientation dispersion within white matter, as a complement to classic DTI measures. Study design: Youth aged 16 to 24 years born with complex CHD and healthy peers underwent brain magnetic resonance imaging. White matter tract volumes and tract-average values of DTI and NODDI metrics were compared between groups. Tract-average DTI and NODDI results were spatially confirmed using tract-based spatial statistics. Results: There were widespread regions of lower tract-average neurite density index (NDI) in the CHD group as compared to the control group, particularly within long association tracts and in regions of the corpus callosum, accompanied by smaller white matter tract volumes and isolated clusters of lower fractional anisotropy (FA). There were no significant differences in orientation dispersion index (ODI) between groups. Conclusion Lower apparent density of axonal packing, but not altered axonal orientation, is a key microstructural factor in the white matter abnormalities observed in youth born with CHD. These impairments in axonal packing may be an enduring consequence of early life brain injury and dysmaturation and may explain some of the long-term neuropsychological difficulties experienced by this at-risk group.