Fetal Brain MRI as a Predictor of Late Neurodevelopmental Outcome in Congenital Heart Disease

项目摘要/摘要 先天性心脏病是最常见的出生缺陷，占所有活产婴儿的0.5%-2%。作为医疗和医疗服务 外科手术的进步极大地提高了存活率，迅速增长的儿童和成人 先天性心脏病暴露了幸存者中神经发育障碍的高患病率。通过 青春期，每3个患有严重先天性心脏病的儿童中就有2个以上经历缺陷 需要发展/特殊教育服务。随着这些孩子成年，他们的残疾可能会 限制教育机会、就业和生活质量。 胎儿脑发育异常可能是先天性脑发育障碍的原因之一 心脏病。先天性心脏病新生儿手术前脑结构异常。 为长期结构大脑组织奠定基础的神经生物学过程始于子宫。 胎脑中对这一过程至关重要的成分，特别是神经前体细胞，在髓鞘形成之前 少突胶质细胞和亚板下神经元对缺氧缺血敏感，使这个系统容易受到 产前循环障碍。胎脑发育异常对长期脑结构的影响 而先天性心脏病的功能尚不清楚。到目前为止，还没有先天性心脏病的队列 在胎儿期和后来的儿童时期都进行了研究，那时通常会检测到这些缺陷。 这项建议将利用现有的胎儿核磁共振队列，包括患有和不患有先天性心脏病的儿童 心脏病，在7岁时获得长期的神经成像和神经发育数据，从而 确定胎儿对长期结局的贡献。具体地说，拟议的研究将调查1) 胎脑结构与学龄期结构性脑连通性的关系 胎儿大脑结构和学龄期神经发育功能之间的关系；以及3)临床应用的可能性 风险分层工具利用宫内可用措施预测学龄期神经发育 结果。最重要的假设是，胎儿大脑结构异常与长期 先天性心脏病患者脑结构连通性和神经发育功能的差异。 该项目将支持临床风险分层的发展，并推动 旨在保护先天性心脏病儿童大脑的干预措施。

PROJECT SUMMARY/ABSTRACT Congenital heart disease is the most common birth defect, affecting 0.5-2% of all live births. As medical and surgical advances have dramatically increased survival, the burgeoning population of children and adults with congenital heart disease has exposed a high prevalence of neurodevelopmental disabilities in survivors. By adolescence, more than 2 out of every 3 children with critical congenital heart disease experience deficits requiring developmental/special education services. As these children reach adulthood, their disabilities may limit educational opportunities, employment, and quality of life. Abnormal fetal brain development may contribute to neurodevelopmental disability in patients with congenital heart disease. Neonates with congenital heart disease have abnormal brain structure before surgery. Neurobiological processes that lay the foundation for long-term structural brain organization begin in utero. Components of fetal brain critical for this process, in particular neural progenitor cells, premyelinating oligodendrocytes, and subplate neurons, are sensitive to hypoxia-ischemia, rendering this system vulnerable to prenatal circulatory disturbances. The impact of abnormal fetal brain development on long-term brain structure and function in congenital heart disease is unknown. To date, there are no congenital heart disease cohorts that have been studied in both the fetal period and later in childhood when these deficits are typically detected. This proposal will leverage an existing fetal MRI cohort, including children both with and without congenital heart disease, to acquire long-term neuroimaging and neurodevelopmental data at 7 years of age, thereby determining the fetal contribution to long-term outcome. Specifically, the proposed study will investigate 1) the association between fetal brain structure and school-age structural brain connectivity; 2) the relationship between fetal brain structure and school-age neurodevelopmental functioning; and 3) the potential for a clinical risk stratification tool harnessing measures available in utero to predict school-age neurodevelopmental outcome. The overarching hypothesis is that abnormal fetal brain structure is associated with long-term differences in structural brain connectivity and neurodevelopmental functioning in congenital heart disease. This project will support the development of clinical risk stratification and advance the development of interventions designed to protect the brain in children with congenital heart disease.