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: 10670209
• 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/10670209
• 关键词: Accounting; Adult; Affect; Age Months; Animal Model; Aorta; Automobile Driving; Biological Markers; Birth; Blood; Blood Vessels; Brain; Cardiac; Cardiac Surgery procedures; Cardiovascular system; 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; Fetal Reduction; Fetus; Foundations; Functional disorder; Gases; Goals; Grant; Health; Heart; Heart Abnormalities; Heterogeneity; Hospital Costs; Human; Hypertension; Immunologics; Impairment; Incidence; Infant; Intervention; Lesion; Link; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mentors; Metabolic; Metabolism; Methods; Modality; Modeling; Motion; Neurocognitive; Neurodevelopmental Impairment; Obesity; Operative Surgical Procedures; Organ; Organogenesis; Outcome; Oxygen; Patients; Pediatric cardiology; Perfusion; Physiology; Placenta; Placenta Diseases; Placentation; Population; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Prenatal Diagnosis; Quality of life; Rehabilitation therapy; Research; Research Design; Research Proposals; Risk; Risk Factors; Role; Scientist; Site; Structure; Survivors; Techniques; Testing; Thrombosis; Time; Training; Variant; Vascularization; Villus; Wood material; Work; blood oxygen level dependent; brain tissue; career; career development; clinically relevant; comparison control; congenital heart disorder; design; epidemiology study; expectation; fetal; hemodynamics; high risk; imaging biomarker; improved; in utero; in vivo; maternal risk; neurodevelopment; neuroimaging; neurological rehabilitation; neuroprotection; 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.

抽象的 先天性心脏病 (CHD) 是最常见的出生缺陷，每年影响约 40,000 名婴儿。 由于诊断和手术技术的进步，患有先心病的成年人首次增加 比美国的孩子还多特别是，先心病幸存者面临不同的神​​经发育和神经认知风险 延误。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，胎盘疾病的发生率有所增加 患有先心病（CHD）的胎儿异常。磁共振成像 (MRI) 是一种安全、非电离的成像方式， 为非侵入性研究子宫内胎儿环境提供了独特的机会。这个提议 旨在阐明使用 MRI 测量的胎盘损伤在确定胎儿和产后的作用 CHD 的神经发育结果。该提案的结果将阐明心脏之间的相互作用如何 生理学、胎盘受损和其他母婴风险导致冠心病结局的异质性。 该提案还旨在为以下人员提供重要的科学培训和职业发展机会： 让 Rajagopalan 博士能够发展为独立的职业，使用非侵入性、基于成像的生物标记物来 加强产前疾病的诊断，促进胎儿治疗和干预，以改善产前疾病 神经发育结果。迄今为止，拉贾戈帕兰博士的工作重点是开发新方法—— 胎儿 MRI 技术和计算技术来回答机械和临床相关问题 有关出生异常的问题。这笔 K01 赠款将有助于 Rajagopalan 博士过渡到独立 通过为她提供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 采集和多站点研究设计； (3) 计算建模，这将使我能够 成为一名独立科学家，专注于增进我们对疾病的理解，并最终促进诊断和治疗 CHD 神经发育结局的管理。为了实现这些培训目标，Rajagopalan 博士 制定了一个培训计划，包括发展方面的教学培训和实践实践 生物学、高级 MR 采集和处理以及临床、儿科心脏病学。有她支持 导师：J. Wood 博士，医学博士，使用非侵入性方法模拟心脏异常血流动力学的专家 核磁共振成像； A. Panigrahy 博士是医学博士，拥有早期神经影像学和心脏神经发育结果方面的专业知识。 培训计划与研究计划一起将为 Rajagopalan 博士的独立研究奠定基础 改善先心病幸存者长期神经发育结果的职业生涯。

项目成果

Brain biomarkers and neuropsychological outcomes of pediatric posterior fossa brain tumor survivors treated with surgical resection with or without adjuvant chemotherapy.

• DOI: 10.1002/pbc.28817
• 发表时间: 2021-03
• 期刊: Pediatric blood & cancer
• 影响因子: 3.2
• 作者: Baron Nelson MC;O'Neil SH;Tanedo J;Dhanani S;Malvar J;Nuñez C;Nelson MD Jr;Tamrazi B;Finlay JL;Rajagopalan V;Lepore N
• 通讯作者: Lepore N

Neurocranium thickness mapping in early childhood.

• DOI: 10.1038/s41598-020-73589-w
• 发表时间: 2020-10-06
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Gajawelli N;Deoni S;Shi J;Linguraru MG;Porras AR;Nelson MD;Tamrazi B;Rajagopalan V;Wang Y;Lepore N
• 通讯作者: Lepore N

The Art, Science, and Secrets of Scanning Young Children.

• DOI: 10.1016/j.biopsych.2022.09.025
• 发表时间: 2023-05-15
• 期刊: Biological psychiatry
• 影响因子: 10.6

Infants with Congenital Adrenal Hyperplasia Exhibit Thalamic Discrepancies in Early Brain Structure.

患有先天性肾上腺增生的婴儿在早期大脑结构中表现出丘脑差异。

• DOI: 10.1159/000529403
• 发表时间: 2023
• 期刊: Hormone research in paediatrics
• 影响因子: 3.2
• 作者: Rajagopalan,Vidya;Overholtzer,LloydN;Kim,WilliamS;Wisnowski,JessicaL;Pickering,TrevorA;Fraga,NicoleR;Javier,Joyce;Mackintosh,Liza;Mirzaian,Christine;Geffner,MitchellE;Kim,MimiS
• 通讯作者: Kim,MimiS

Fetal neurodevelopmental recovery in donors after laser surgery for twin-twin transfusion syndrome.

• DOI: 10.1002/pd.5866
• 发表时间: 2021-01
• 期刊: Prenatal diagnosis
• 影响因子: 3
• 作者: Rajagopalan V;Ashouri K;Llanes A;Vanderbilt DL;Lepore N;Bluml S;Lai HA;Wisnowski J;Chon AH;Chmait RH
• 通讯作者: Chmait RH