Brain microstructure and morphology of very preterm-born infants at term equivalent age: Associations with motor and cognitive outcomes at 1 and 2 years

Very preterm-born infants are at risk of adverse neurodevelopmental outcomes. Brain magnetic resonance imaging (MRI) at term equivalent age (TEA) can probe tissue microstructure and morphology, and demonstrates potential in the early prediction of outcomes. In this study, we use the recently introduced fixel-based analysis method for diffusion MRI to investigate the association between microstructure and morphology at TEA, and motor and cognitive development at 1 and 2 years corrected age (CA). Eighty infants born <31 weeks' gestation successfully underwent diffusion MRI (3T; 64 directions; b = 2000s/mm(2)) at term equivalent age, and had neurodevelopmental follow-up using the Bayley-III motor and cognitive assessments at 1 year (n = 78) and/or 2 years (n = 76) CA. Diffusion MRI data were processed using constrained spherical deconvolution (CSD) and aligned to a study-specific fibre orientation distribution template, yielding measures of fibre density (FD), fibre-bundle cross-section (FC), and fibre density and bundle cross-section (FDC). The association between FD, FC, and FDC at TEA, and motor and cognitive composite scores at 1 and 2 years CA, and change in composite scores from 1 to 2 years, was assessed using whole-brain fixel-based analysis. Additionally, the association between diffusion tensor imaging (DTI) metrics (fractional anisotropy FA, mean diffusivity MD, axial diffusivity AD, radial diffusivity RD) and outcomes was investigated. Motor function at 1 and 2 years CA was associated with CSD-based measures of the bilateral corticospinal tracts and corpus callosum. Cognitive function was associated with CSDbased measures of the midbody (1-year outcomes only) and splenium of the corpus callosum, as well as the bilateral corticospinal tracts. The change in motor/cognitive outcomes from 1 to 2 years was associated with CSDbased measures of the splenium of the corpus callosum. Analysis of DTI-based measures showed overall less extensive associations. Post-hoc analysis showed that associations were weaker for 2-year outcomes than they were for 1-year outcomes. Infants with better neurodevelopmental outcomes demonstrated higher FD, FC, and FDC at TEA, indicating better information transfer capacity which may be related to increased number of neurons, increased myelination, thicker bundles, and/or combinations thereof. The fibre bundles identified here may serve as the basis for future studies investigating the predictive ability of these metrics.