Influence of placental impairments and maternal-fetal environment on neurodevelopmental outcomes in Congenital Heart Disease

摘要 先天性心脏病(CHD)是最常见的出生缺陷，每年影响约4万名婴儿。 由于诊断和手术技术的进步，第一次有更多的成年人患有冠心病 而不是美国的孩子。特别是，冠心病幸存者在神经发育和神经认知方面面临着不同的风险。 耽搁了。迫切需要了解推动神经发育结局的各种危险因素。 这群人。在怀孕期间，胎盘与心脏一起发育，对健康至关重要。 胎儿的发育。最近的证据表明，胎盘的发病率有所增加。 先天性心脏病胎儿的异常表现。磁共振成像(MRI)是一种安全、非电离的方式， 为无创研究胎儿宫内环境提供了一个独特的机会之窗。这项建议 旨在阐明胎盘损伤在确定胎儿和出生后的过程中所起的作用。 冠心病患者的神经发育结局。这项提案的发现将阐明心脏之间的相互作用 生理、胎盘受损和其他母胎风险导致CHD结局的异质性。 该提案还旨在提供重要的科学培训和职业发展机会，以 允许Rajagopalan博士在使用基于成像的非侵入性生物标记物方面发展到独立的职业生涯 加强产前疾病的诊断，促进胎儿治疗和干预，目的是改善 神经发育结果。到目前为止，拉贾戈帕兰博士的工作重点是开发新的方法-- 胎儿MRI技术和计算机技术都可以回答机械和临床相关的问题 关于出生异常的问题。这笔K01赠款将促进Rajagopalan博士过渡到独立的 为她的研究生涯提供必要的技能：(1)心脏生理学和发育生物学；(2) 先进的磁共振成像采集和多点研究设计；以及(3)计算建模，使我能够 成为一名独立科学家，专注于促进我们对诊断和最终诊断的理解 冠心病患者神经发育结局的管理。为了实现这些培训目标，拉贾戈帕兰博士 已经制定了一项培训计划，包括教学培训和发展中的动手实践 生物学、高级磁共振获取和处理，以及临床和儿科心脏病学。她靠她养活 导师：J.Wood M.D.博士，心脏异常的非侵入性血流动力学建模专家 核磁共振；A.Panigrahy医学博士，在早期神经成像和心脏神经发育结果方面拥有专业知识。 与研究提案一起，培训计划将为Rajagopalan博士的独立 改善冠心病幸存者长期神经发育结果的职业生涯。

ABSTRACT Congenital heart disease (CHD) is the most common birth defect, affecting around 40,000 infants each year. Due to advances in diagnosis and surgical techniques, for the first time, there are more adults living with CHD than children in the US. Particularly, CHD survivors are at varied risk for neurodevelopmental and neurocognitive delays. There is a pressing need to understand the various risk factors driving neurodevelopmental outcome in this population. During gestation, the placenta develops concomitantly with the heart and is critical to healthy development of the fetus. Recent evidence has shown that there is increased incidence of placental abnormalities in fetuses with CHD. Magnetic resonance imaging (MRI) is a safe, non-ionizing modality and provides a unique window of opportunity to non-invasively study the fetal environment, in-utero. This proposal seeks to elucidate the role of placental impairments, measured using MRI, in determining fetal and postnatal neurodevelopmental outcomes in CHD. Findings from this proposal will clarify how interactions between cardiac physiology, impaired placenta and other maternal-fetal risks drive heterogeneity of outcomes in CHD. This proposal is also designed to provide important scientific training and career development opportunities to allow Dr. Rajagopalan to advance to an independent career in using non-invasive, imaging-based biomarkers to enhance diagnosis of prenatal disorders and facilitate fetal therapy and intervention with a goal of improving neurodevelopmental outcomes. Dr. Rajagopalan’s work, thus far, has focused on developing novel methods – both fetal MRI techniques and computational techniques to answer both mechanistic and clinically relevant questions around birth anomalies. This K01 grant will facilitate Dr. Rajagopalan’s transition to an independent research career by providing her the necessary skills in: (1) cardiac physiology and developmental biology; (2) advanced MRI acquisition and multi-site study design; and (3) computational modeling that will allow me to become an independent scientist focused on advancing our understanding of, and ultimately the diagnosis and management of neurodevelopmental outcomes in CHD. In order to achieve these training goals, Dr. Rajagopalan has put together a training plan that comprises of didactic training and hands-on practica in developmental biology, advanced MR acquisition and processing, and clinical, pediatric cardiology. She is supported by her mentors: Dr. J. Wood M.D., an expert in in modeling hemodynamics in cardiac abnormalities using non-invasive MRI; Dr. A. Panigrahy M.D., with expertise in early neuroimaging and cardiac-neurodevelopmental outcomes. Together with the research proposal, the training plan will lay the foundation for Dr. Rajagopalan’s independent career in improving long-term neurodevelopmental outcomes in CHD survivors.