Spatiotemporal Atlas of the Fetal Brain Depicts Cortical Developmental Gradient

The fetal brains experience rapid and complex development in utero during the second and third trimesters. In utero MRI of the fetal brain in this period enables us to quantify normal fetal brain development in the spatiotemporal domain. In this study, we established a high-quality spatiotemporal atlas between 23 and 38 weeks gestational age (GA) from 90 healthy Chinese human fetuses of both sexes using a pairwise and groupwise registration pipeline. We quantified the fetal cortical morphology indices and characterized their spatiotemporal developmental pattern. The cortical thickness exhibited a biphasic pattern that first increased and then decreased; the curvature fitted well into the Gompertz growth model; sulcal depth increased linearly, while surface area expanded exponentially. The cortical thickness and curvature trajectories consistently pointed to a characteristic time point around GA of 31 weeks. The characteristic GA and growth rate obtained from individual cortical regions suggested a central-to-peripheral developmental gradient, with the earliest development in the parietal lobe, and we also observed a superior-to-inferior gradient within the temporal lobe. These findings may be linked to biophysical events, such as dendritic arborization and thalamocortical fibers ingrowth. The proposed atlas was also compared with an existing fetal atlas from a white/mixed population. Finally, we examined the structural asymmetry of the fetal brains and found extensive asymmetry that dynamically changed with development. The current study depicted a comprehensive profile of fetal cortical development, and the established atlas could be used as a normative reference for neurodevelopmental and diagnostic purposes, especially in the Chinese population.SIGNIFICANCE STATEMENT We generated a high-quality 4D spatiotemporal atlas of the normal fetal brain development from 23 to 38 gestational weeks in a Chinese population and characterized the spatiotemporal developmental pattern of cortical morphology. According to the cortical development trajectories, the fetal cerebral cortex development follows a central-to-peripheral developmental gradient that may be related to the underlying cellular events. The majority of cortical regions already exhibit significant asymmetry during the fetal period.