Cortical maturation was studied in 65 infants between 27 and 46 wk postconception using structural and diffusion magnetic resonance imaging. Alterations in neural structure and complexity were inferred from changes in mean diffusivity and fractional anisotropy, analyzed by sampling regions of interest and also by a unique whole-cortex mapping approach. Mean diffusivity was higher in gyri than sulci and in frontal compared with occipital lobes, decreasing consistently throughout the study period. Fractional anisotropy declined until 38 wk, with initial values and rates of change higher in gyri, frontal and temporal poles, and parietal cortex; and lower in sulcal, perirolandic, and medial occipital cortex. Neuroanatomical studies and experimental diffusion-anatomic correlations strongly suggested the interpretation that cellular and synaptic complexity and density increased steadily throughout the period, whereas elongation and branching of dendrites orthogonal to cortical columns was later and faster in higher-order association cortex, proceeding rapidly before becoming undetectable after 38 wk. The rate of microstructural maturation correlated locally with cortical growth, and predicted higher neurodevelopmental test scores at 2 y of age. Cortical microstructural development was reduced in a dose-dependent fashion by longer premature exposure to the extrauterine environment, and preterm infants at term-corrected age possessed less mature cortex than term-born infants. The results are compatible with predictions of the tension theory of cortical growth and show that rapidly developing cortical microstructure is vulnerable to the effects of premature birth, suggesting a mechanism for the adverse effects of preterm delivery on cognitive function. brain development | DTI | preterm birth D endritic arborization and synapse formation increase within the cerebral cortical plate from midgestation, transforming the cortex from a predominantly radial formation arrayed perpendicular to the cortical surface into a denser, more complex structure with large numbers of neural connections running parallel to the surface (1). Several groups have related this microstructural maturation to changes in the rate and principal direction of water diffusion within the cortex observed in vivo by diffusion tensor imaging (DTI) (2-5). It is proposed that increasing cellular density and complexity lead to a decrease in tissue water content and a fall in mean diffusivity (MD) (6-9), whereas decreases in the relative fraction of water diffusion perpendicular to the cortical surface, measured as a decline in fractional anisotropy (FA), reflect neurite outgrowth and maturing dendritic cytoarchitecture (7,8,(10)(11)(12). These changes have been measured in neonatal piglets (13), cats (14), and mice (15), and in pioneering studies of preterm infants (3,4,8).The present study used structural MRI and DTI to examine the spatial and temporal development of human cortical microstructure. We reasoned that if the process was impaired by preterm birth we...

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