LONGITUDINAL ANALYSIS OF CEREBRAL CORTICAL DEVELOPMENT IN UTERO

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abnormal development of the cerebral cortex during the gestational period results in long-term cognitive impairments that are behaviorally detectable years after birth. The goal of the proposed experiments is to develop MRI capabilities for monitoring cerebral cortical development, and detecting developmental abnormalities, in utero. We will perform longitudinal MRI measurements of fetal brain development throughout the second half of gestation in normal Japanese macaques, and compare our findings to fetuses subjected to a maternal high-fat diet. A recently-described imaging technique will be applied to obtain high-quality in utero brain images. Cortical surface models will be constructed using the MRI data, and microstructural changes associated with cortical development will be monitored using diffusion tensor imaging (DTI) techniques. With this data, we aim to 1) test a hypothesized relationship between microstructural changes and cerebral cortical surface area expansion, and 2) determine whether hypothesized alterations in cortical development are observed in fetuses experiencing a high-fat maternal environment. Through this unique opportunity to perform longitudinal measurements in a non-human primate, we will explore the potential role of proinflammatory cytokine expression on cortical development and provide new insight into the biological mechanisms that give rise to cortical surface expansion with development.