Imaging early development of human neural circuits

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Imaging early development of human neural circuits The overall objective of this research is to create new imaging technology that dramatically improves our ability to analyze the development of brain function and functional networks before birth. Functional magnetic resonance imaging (fMRI) provides a unique capability to study neural circuits and brain functional connections in-vivo. Fetal fMRI acquisition and analysis, however, has been hampered by three important challenges: 1) fetal motion disrupts the spatial and temporal continuity of the MRI signal, 2) geometric distortion is exacerbated by the motion of fetal and maternal organs, and 3) the anatomy and function of the developing fetal brain is distinctly different from those of young children and adults, thus current processing pipelines and atlases are inadequate for reliable fetal fMRI analysis. To address these challenges, we pursue three specific aims in this study, that are focused on 1) developing a prospectively motion navigated fetal fMRI acquisition technology, based on fast real-time image processing, that compensates for the fetal head motion and geometric distortions during acquisitions; 2) developing a post-acquisition processing technique that reconstructs an fMRI time series from motion- corrected fetal fMRI data that are scattered in space and time because of motion and motion correction; and 3) assessing the utility of fetal fMRI and the developed technologies to evaluate early development of neural circuits and brain function in fetuses with congenital heart disease compared to healthy fetuses. This contribution is important because it 1) mitigates a critical barrier to making progress in the field of developmental neurology and neuroscience by allowing reliable use of fetal fMRI in studying normal vs. abnormal development of the brain function; 2) improves the efficiency and efficacy of fetal fMRI through prospectively adjusting scans to compensate for motion and geometric distortions, thus strengthens our ability to study large cohorts; 3) provides tools and resources, including atlas-based parcellation and a processing pipeline for the analysis of fetal fMRI; and 4) generates important knowledge about the origins of disrupted neural development due to hypoxia ischemia in congenital heart disease. The technology, resources, and knowledge developed in this study have a broad impact and are crucial for advanced studies in developmental neuroscience and neurology, aiming to elucidate the potentially devastating effects of adverse early life conditions including congenital disorders of the brain and heart. It is hoped that these studies lead to improved understanding of the underlying causes of neurodevelopmental disorders, leading to preventive strategies, therapies, and in some cases, cure.