Enhanced Imaging of the Fetal Brain Microstructure The fetal period of brain development is critical as it involves complex processes of cell proliferation, neuronal migration, and myelination that are particularly vulnerable to disturbances from adverse events in utero and conditions that develop during gestation. Specifically, hypoxia caused by abnormal circulation, is hypothesized to disrupt neuronal migration thereby causing altered brain connectivity and adverse neurological outcomes. Abnormal brain connectivity has been depicted in newborns and adolescents with critical congenital heart disease (CHD) using diffusion-weighted imaging (DWI). Gross brain abnormalities have also been identified and quantified prenatally in CHD using in utero T2-weighted magnetic resonance imaging (MRI), but the precise location and timing of disrupted neuronal migration that leads to these abnormalities, has remained unclear due to technological limitations of in utero DWI. In this project we aim at developing new DWI technologies that remove these barriers to improve our understanding of the maturation of fetal brain microstructure as well as the origins and patterns of its alterations in utero. In particular, we aim to develop new techniques to address the limitations of current fetal DWI technology by effectively mitigating and compensating for motion and geometric distortion artifacts during acquisitions. This project therefore seeks to create a paradigm shift in the way fetal DWI is acquired and analyzed. The three specific aims of the project are to 1) create a prospectively motion-corrected slice navigation system for fetal brain DWI, 2) enhance fetal DWI acquisitions with artifact reduction and compensation by developing new imaging and image reconstruction techniques for dynamic field mapping, and 3) evaluate fetal brain maturation in congenital heart disease. We will assess the utility and impact of the technologies developed in this project by analyzing and comparing a large pre-existing cohort of fetal DWI scans with the scans prospectively acquired from both typically-developing (TD) and CHD fetuses with these new techniques. Moreover, we expect to gain important knowledge about early disruptions to neuronal migration pathways and formation of brain connections due to compromised circulation and hypoxia in fetuses with CHD. By making fetal DWI more reliable and robust, this study will mitigate a critical barrier to making progress in the fields of developmental neurology and neuroscience. Improved understanding of the impact of adverse events in utero on fetal brain growth and the trajectories of altered brain development can help guide neuroprotective and therapeutic interventions, and enable early, more effective treatments for neurological diseases and mental disorders. Fetal DWI plays a crucial role in establishing such an understanding as it is uniquely able to depict the microstructure of the fetal brain in utero.

Project Narrative: The proposed research aims to develop innovative technologies to image brains of unborn babies in utero, and to apply those techniques to study development of brain structure and connections before birth. The technology developed, and the knowledge gained in this study, is expected to guide early treatments and therapeutic interventions to improve neurodevelopmental outcomes in babies with congenital disorders.