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

Rachel Leon，MD，PhD是一名新生儿-围产期医学医生，拥有UT神经科学博士学位 西南医学中心（UTSW）她的目标是成为一名独立资助的调查员， 神经胎盘学的专业知识，这一领域的重点是阐明胎盘对胎儿影响的机制 大脑发育她计划研究先天性心脏病胎儿的胎盘和脑血管血流动力学 心脏病（CHD），使用先进的成像技术。在胎儿被诊断为左或 右室流出道梗阻CHD（分别为LVOTO和RVOTO），和健康对照组，她 具体目的是1）纵向评估胎盘灌注并确定 胎盘大小和组织病理学，2）确定胎盘灌注对脑自动调节的影响， 胎儿期到出生后早期的适应，以及3）确定胎盘灌注如何影响轨迹 大脑区域性生长。Leon博士将联合收割机结合动脉自旋标记磁共振成像（MRI）， 测定妊娠期两个时间点胎盘血流灌注与胎盘病理评价的探讨 灌注异常的组织病理学基础。应用连续多普勒超声检查大脑中动脉 和脐动脉，以及产后大脑近红外光谱和血压，她将 确定从出生前到出生后大脑自动调节的成熟变化，以及这是如何发生的。 与胎盘灌注有关。她将在产前进行两次胎儿脑MRI，并在产后早期再次进行 期间，以确定胎盘灌注与局部脑生长轨迹的关系。里昂医生的 研究CHD胎盘-脑连接的创新方法将阐明可能的病理生理学 CHD人群大脑发育受损的机制，这是发现CHD的必要的第一步。 有针对性的胎儿干预。Leon博士组建了一个由导师和合作者组成的多学科团队， 在关键领域的专业知识：大脑自动调节（Lina Chalak，医学博士），先进的胎盘和胎儿成像（Diane Twickler，MD和Ashok Panigrahy，MD），胎盘生理学（Catherine Spong，MD和Dinesh Rakheja，MD）， 和CHD（Mohammad Tarique Hussain，MD，PhD）。UTSW医院系统及其强大的临床研究 操作是理想的环境进行拟议的研究与他们强大的胎儿心脏计划， 专门的转化医学中心，以及参与临床研究的良好记录。里昂医生的 职业发展计划包括一个全面的战略，以解决具体的关键培训目标， 将使她能够建立她的研究计划，包括1）获得先进的胎儿大脑的专业知识， 胎盘MRI技术及其与病理生理学的相关性，2）发展成熟的 大脑自动调节机制和分析工具，以评估这些动态信号，和3）开发 领导能力的临床研究，涉及母胎二对。与她的科学目标一起，这些目标 将为Leon博士提供必要的技能，以建立她在神经胎盘学方面的独立研究计划。

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.