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

胎盘损伤和母胎环境对先天性心脏病神经发育结局的影响

• 批准号: 10041130
• 负责人: Vidya Rajagopalan
• 金额: $ 14.69万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-10 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10041130
• 关键词: Accounting; Adult; Affect; Age-Months; Animal Model; Automobile Driving; Biological Markers; Birth; Blood; Blood Vessels; Brain; Cardiac; Child; Clinical; Communities; Complex; Computational Technique; Computer Models; Congenital Abnormality; Development; Developmental Biology; Diabetes Mellitus; Diagnosis; Diagnostic; Doctor of Medicine; Endocrine; Environment; Exhibits; Fetal Development; Fetus; Foundations; Functional disorder; Gases; Goals; Grant; Health; Heart; Heart Abnormalities; Heterogeneity; Hospitals; Human; Hypertension; Imaging Techniques; Immunologics; Impairment; Incidence; Infant; Intervention; Lesion; Link; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mentors; Metabolic; Metabolism; Methods; Modality; Modeling; Motion; Neurocognitive; Obesity; Operative Surgical Procedures; Organ; Outcome; Oxygen; Patients; Pediatric cardiology; Perfusion; Physiology; Placenta; Placenta Diseases; Placentation; Population; Pre-Eclampsia; Pregnancy; Prenatal Diagnosis; Quality of life; Rehabilitation therapy; Research; Research Design; Research Proposals; Risk; Risk Factors; Role; Scientist; Site; Structure; Survivors; Techniques; Testing; Time; Training; Variant; Villus; Wood material; Work; base; blood oxygen level dependent; brain tissue; career; career development; clinically relevant; congenital heart disorder; design; epidemiology study; expectation; fetal; hemodynamics; high risk; imaging biomarker; improved; in utero; in vivo; maternal risk; neurodevelopment; neuroimaging; non-invasive imaging; novel; nutrition; postnatal; prenatal; prenatal disorder; prenatal therapy; skills; spatiotemporal; surgery outcome; vascular abnormality

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.

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CHD 比美国的孩子多。特别是，CHD幸存者在神经发育和神经认知方面的风险不同。 延误了.有迫切需要了解驱动神经发育结果的各种风险因素， 这个人口。在妊娠期间，胎盘与心脏同时发育，对胎儿的健康至关重要。 胎儿的发育。最近的证据表明，胎盘炎的发生率增加， CHD胎儿的异常。磁共振成像（MRI）是一种安全的非电离方式， 提供了一个独特的机会窗口，以非侵入性地研究胎儿环境，在子宫内。这项建议 试图阐明胎盘损伤的作用，使用MRI测量，在确定胎儿和产后 CHD的神经发育结局。这项提案的结果将阐明心脏与心脏之间的相互作用 生理学、胎盘受损和其他母胎风险导致CHD结局的异质性。 这项建议还旨在为以下人员提供重要的科学培训和职业发展机会： 允许Rajagopalan博士在使用非侵入性，基于成像的生物标志物方面发展独立的职业生涯， 加强产前疾病的诊断，促进胎儿治疗和干预， 神经发育结果。到目前为止，Rajagopalan博士的工作集中在开发新的方法上- 胎儿MRI技术和计算技术来回答机械和临床相关 关于出生异常的问题这K 01赠款将促进博士Rajagopalan的过渡到一个独立 通过提供她在以下方面的必要技能来促进她的研究生涯：（1）心脏生理学和发育生物学;（2） 先进的MRI采集和多中心研究设计;（3）计算建模，使我能够 成为一名独立的科学家，专注于推进我们对疾病的理解，并最终诊断和 CHD神经发育结局的管理。为了实现这些培训目标，Rajagopalan博士 已经制定了一个培训计划，包括教学培训和实践， 生物学、高级MR采集和处理以及临床、儿科心脏病学。她支持她的 导师：J. Wood医学博士，他是一位使用非侵入性方法对心脏异常进行血液动力学建模的专家， 核磁共振成像; A. Panigrahy医学博士，在早期神经影像学和心脏神经发育结果方面具有专业知识。 与研究建议一起，培训计划将为Rajagopalan博士的独立工作奠定基础。 改善CHD幸存者的长期神经发育结局。