Characterization of normative fetal rhesus macaque brain development with magnetic resonance imaging.

Abstract

Advances in motion correction magnetic resonance imaging methods have made it possible to track anatomical changes throughout the highly dynamic phase of fetal neurodevelopment. Characterizing the trajectory of normative brain development provides insight into the underlying biological processes driving growth, as well as a framework for identifying deviations that may be etiological markers of neurodevelopmental disorders. Rhesus macaques, which exhibit similar gestational neurodevelopmental timelines to humans, can be used to address the challenges of obtaining accurate longitudinal fetal imaging measurements and are a key preclinical resource for investigating experimental developmental perturbations. Additionally, the ability to examine biological factors including age and sex can provide important information regarding individual variability in development, but this is often precluded due to limitations in nonhuman primate samples, especially during gestation. To provide updated rhesus macaque magnetic resonance fetal templates allowing for the characterization of normative neurodevelopmental trajectories, we leveraged a unique, large mixed-longitudinal sample of 50 normally developing rhesus macaque fetuses (28 female and 22 male) scanned longitudinally and cross-sectionally in utero (105 scans) across the second half of gestation (post-conception gestational day (G) 85, G97, G110, G122, G135, G147, and G155; of a 165-day term). We generated anatomically segmented T₂-weighted and mid-cortical surface templates at these ages, as well as a 4-year-old post-pubertal young adult template (10 female and 10 male) with corresponding fetal consistent anatomical segmentations for comparisons of fetal-to-adult values, which we provide to the neuroscience imaging community. In characterizing shape morphological features (surface area, curvature, and thickness) and volumetric brain development throughout the second half of gestation, we identify evidence of sexual dimorphism in rhesus macaque fetal brain growth and compare patterns of cortical development with findings from other species.