Placental hemodynamic effects on brain development in infants with congenital heart disease

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Rachel Leon, MD, PhD is a Neonatal-Perinatal Medicine physician with a PhD in neuroscience at UT Southwestern Medical Center (UTSW). Her goal is to become an independently funded investigator with expertise in neuroplacentology, a field that focuses on elucidating mechanisms of placental influence on fetal brain development. She plans to study placental and cerebrovascular hemodynamics in fetuses with congenital heart disease (CHD) using advanced imaging techniques. In pregnant people with fetuses diagnosed with left or right ventricular outflow tract obstruction CHD (LVOTO and RVOTO, respectively), and healthy controls, her specific aims are to 1) evaluate placental perfusion longitudinally and determine associated differences in placental size and histopathology, 2) determine the impact of placental perfusion on cerebral autoregulation from the fetal period to the early postnatal adaptation, and 3) determine how placental perfusion affects the trajectory of regional brain growth. Dr. Leon will combine arterial spin labeling magnetic resonance imaging (MRI) to determine placental perfusion at two timepoints in pregnancy with pathologic evaluation of placentas to explore histopathologic underpinnings of perfusion abnormalities. Using serial Doppler ultrasound of the middle cerebral and umbilical arteries, as well as postnatal cerebral near infrared spectroscopy and blood pressure, she will determine the maturational changes of cerebral autoregulation from prenatal to postnatal life, and how this relates to placental perfusion. She will perform fetal brain MRI twice prenatally and again in the early postnatal period to determine the relationship of placental perfusion to the trajectory of regional brain growth. Dr. Leon’s innovative approach to studying the CHD placenta-brain connection will elucidate possible pathophysiologic mechanisms for impaired brain development in the CHD population, a necessary first step for the discovery of targeted fetal interventions. Dr. Leon has assembled a multidisciplinary team of mentors and collaborators with expertise in key areas: cerebral autoregulation (Lina Chalak, MD), advanced placental and fetal imaging (Diane Twickler, MD and Ashok Panigrahy, MD), placental physiology (Catherine Spong, MD and Dinesh Rakheja, MD), and CHD (Mohammad Tarique Hussain, MD, PhD). The UTSW hospital system and its strong clinical research operation are the ideal environment to conduct the proposed studies with their robust Fetal Heart Program, a dedicated Center for Translational Medicine, and a strong record of clinical research participation. Dr. Leon’s Career Development Plan includes a comprehensive strategy to address the specific key training goals that will allow her to establish her research program, including 1) gaining expertise in advanced fetal brain and placental MRI techniques and their correlation to pathophysiology, 2) developing expertise in the maturation of cerebral autoregulatory mechanisms and analytical tools to evaluate these dynamic signals, and 3) developing leadership skills for clinical research involving maternal-fetal dyads. Together with her scientific aims, these goals will provide the skills necessary for Dr. Leon to build her independent research program in neuroplacentology.