Fetal Brain Development in Congenital Heart Disease

项目总结/摘要 先天性心脏病是最常见的出生缺陷之一，影响所有活产婴儿的1-2%。而 外科手术的进步极大地提高了生存率，许多患者面临终身的神经系统后遗症， 大大降低了生活质量。虽然出生后的医疗因素可能会影响神经系统的结果，最近 胎儿核磁共振成像数据表明，异常的大脑发育始于子宫内。此外，大脑发育不良 预测神经发育的结果。在子宫内的神经保护治疗可以防止或减少 某些先天性心脏病患者的神经系统后遗症。 本研究旨在探讨先天性心脏病胎儿脑发育的影响因素， 对胎儿神经保护定量方法的认识。该提案将解决目前存在的三个关键差距。 知识：（1）先天性心脏病脑结构异常的区域特异性和发病时间 疾病;（2）导致胎儿大脑发育异常的生理机制;以及（3）胎儿 大脑与神经发育结果的相关性。该研究将采用创新的结构MRI技术， 解决这些目标，利用最先进的MRI处理工具来纠正胎儿运动， 胎儿神经成像的主要局限性。孕妇在怀孕期间将接受两次胎儿MRI， 出生后的孩子将在两岁时接受神经发育测试。这一发现 研究将阐明先天性心脏病大脑发育异常机制， 发展胎儿疗法以减轻先天性心脏病的神经影响。 这种指导以病人为导向的职业发展奖申请符合国家的目标， 神经疾病和中风研究所，因为它将澄清这一人群的异常大脑发育 并阐明保护大脑的潜在策略。该提案还旨在提供重要的 提供培训和职业发展机会，使候选人能够成为独立的 先天性心脏病神经保护研究者。罗林斯医生有使用 神经成像工具来了解先天性心脏病大脑结构的异常， 获奖后，她将获得1）通过实际实验室暴露的先进MRI技术培训，2）临床 流行病学通过正式MPH课程，和3）临床试验方法。她将受益于 极其丰富的心脏神经病学和神经影像学培训环境，她将在其中培养技能 应用尖端的神经影像技术来回答神经生物学问题。最终，这项研究 提案和伴随的培训将为成功的独立研究提供坚实的基础 致力于减少先天性心脏病的神经后遗症的职业。

PROJECT SUMMARY/ABSTRACT Congenital heart disease is among the most common birth defects, affecting 1-2% of all live births. While surgical advances have dramatically improved survival, many patients face life-long neurological sequelae that substantially reduce quality of life. While postnatal medical factors may influence neurological outcome, recent fetal MRI data suggest that abnormal brain development begins in utero. Furthermore, cerebral dysmaturation at birth predicts neurodevelopmental outcome. In utero neuroprotective therapies may prevent or reduce neurological sequelae for patients with certain forms of congenital heart disease. This proposal investigates factors influencing fetal brain development in congenital heart disease to give insight into ration methods for fetal neuroprotection. The proposal will address three key gaps in current knowledge: (1) the regional specificity and timing of onset of abnormal brain structure in congenital heart disease; (2) the physiological mechanisms that lead to abnormal fetal brain development; and (3) the fetal brain correlates of neurodevelopmental outcome. The study will employ innovative structural MRI techniques to address these aims, harnessing cutting edge MRI processing tools to correct for fetal motion and address one of the major limitations of fetal neuroimaging. Pregnant women will undergo fetal MRI twice during pregnancy, and after birth children will undergo neurodevelopmental testing at two years of age. The findings from this investigation will clarify mechanisms of abnormal brain development in congenital heart disease and inform development of fetal therapies to mitigate the neurological effects of congenital heart disease. This Mentored Patient-Oriented Career Development Award application aligns with the goals of the National Institute of Neurological Disorders and Stroke, as it will clarify abnormal brain development in this population and shed light on potential strategies to protect the brain. The proposal is also designed to provide important opportunities for training and career development to enable the candidate to become an independent investigator addressing neuroprotection in congenital heart disease. Dr. Rollins has experience in using neuroimaging tools to understand abnormalities in brain structure in congenital heart disease, and with this award, she will gain training in 1) advanced MRI techniques through practical laboratory exposure, 2) clinical epidemiology through a formal MPH curriculum, and 3) clinical trial methods. She will benefit from an enormously rich cardioneurology and neuroimaging training environment, where she will develop skills in applying cutting edge neuroimaging technology to answer neurobiological questions. Ultimately, this research proposal and the accompanying training will provide a strong foundation for a successful independent research career devoted to minimizing the neurological sequelae of congenital heart disease.