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Antecedents of Impaired Brain Development in Fetuses with Heart Disease

患有心脏病的胎儿大脑发育受损的前因

基本信息

批准号：
9242689
负责人：
Catherine Limperopoulos
金额：
$ 69.78万
依托单位：
CHILDREN'S RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9242689
关键词：
Address Age-Months Anaerobic Bacteria Biological Markers Blood Circulation Brain Brain Injuries Cardiac Surgery procedures Cerebral cortex Cerebrovascular Circulation Cerebrum Complication Cross-Sectional Studies Data Development Developmental Disabilities Doppler Echocardiography Environment Failure Fetus Functional disorder Future Goals Growth Growth and Development function Health Heart Diseases Hypoplastic Left Heart Syndrome Imaging Techniques Impairment Individual Infant Intervention Literature Longevity Longitudinal Studies Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Metabolism Methods Morbidity - disease rate N-acetylaspartate Neonatal Neurologic Neurologic Dysfunctions Neurons Newborn Infant Operative Surgical Procedures Outcome Oxygen Perfusion Placenta Population Pre-Eclampsia Procedures Protons Quality of life Research Proposals Risk Risk Marker Role Second Pregnancy Trimester Subgroup Survivors Third Pregnancy Trimester Time Vascular resistance Work aortic arch brain metabolism brain size cerebral hemodynamics cerebrovascular congenital heart disorder falls fetal hazard hemodynamics high risk imaging modality impaired brain development in vivo infancy insight mortality neurodevelopment neuroprotection outcome prediction postnatal potential biomarker predictive marker prenatal prevent public health relevance repaired therapeutic development therapy development

项目摘要

DESCRIPTION (provided by applicant): .In the management of congenital heart disease (CHD) has markedly reduced mortality. However, brain injury remains a major impediment to high quality of life in survivors. A growing body of literature suggests that a substantial component of this neurologic morbidity may be prenatal in origin. Our studies in CHD fetuses showed for the first time that impaired brain development occurs predominantly in the third trimester and is associated with evidence of impaired brain perfusion and anaerobic metabolism. The mechanism by which CHD disrupts fetal brain development remains unclear. We have developed and validated methods to safely and reliably quantify brain development and metabolism in the living fetus, and newborn using advanced magnetic resonance imaging (MRI) techniques. In the current proposal, we plan to apply echocardiographic measures of the fetal circulation (as well as quantitative MRI methods) to identify the earliest biomarkers for impaired brain development in the fetus with CHD. We will accomplish this by addressing the following specific aims: 1) to determine whether abnormalities in cortical development and brain metabolism (by quantitative MRI and Magnetic Resonance Spectroscopy) are an early marker for risk of impaired volumetric brain growth in the fetus with CHD compared to control fetuses, 2) to determine whether systemic and cerebral hemodynamic perfusion abnormalities (by echocardiography/Doppler US) predict impaired brain growth and/or elevated cerebral lactate in the fetus with CHD versus controls, and 3) to examine the early and long-term neurodevelopmental significance of fetal biomarkers for impaired brain development identified in aims 1 and 2. Our goal is to develop the capacity to reliably and non-invasively identify fetuses with CHD at risk for early brain injury. This, in turn, will begin to open windows for the development of therapeutic interventions aimed at preventing or limiting impaired brain development in these high-risk fetuses.

描述（申请人提供）：。在先天性心脏病（CHD）的管理显著降低死亡率。然而，脑损伤仍然是幸存者高质量生活的主要障碍。越来越多的文献表明，这种神经系统疾病的一个重要组成部分可能是产前起源。我们对CHD胎儿的研究首次表明，大脑发育受损主要发生在妊娠晚期，并与脑灌注和无氧代谢受损有关。冠心病破坏胎儿大脑发育的机制尚不清楚。我们已经开发并验证了使用先进的磁共振成像（MRI）技术安全可靠地量化活胎和新生儿大脑发育和代谢的方法。在目前的提案中，我们计划应用超声心动图测量胎儿循环（以及定量MRI方法）来识别患有冠心病的胎儿大脑发育受损的最早生物标志物。为此，我们将从以下几个方面着手：1)确定皮质发育和脑代谢异常（通过定量MRI和磁共振波谱）是否为冠心病胎儿与对照组相比脑容量发育受损风险的早期标志；2)确定全身和脑血流动力学灌注异常（通过超声心动图/多普勒超声）是否预测冠心病胎儿与对照组相比脑发育受损和/或脑乳酸升高。3)研究目的1和目的2中发现的胎儿生物标志物对大脑发育受损的早期和长期神经发育的意义。我们的目标是发展一种可靠的、无创的识别有早期脑损伤风险的CHD胎儿的能力。反过来，这将开始为旨在预防或限制这些高危胎儿大脑发育受损的治疗干预措施的发展打开窗口。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Disrupted Functional Brain Connectome in the Fetus With Congenital Heart Disease.

患有先天性心脏病的胎儿的功能性脑连接组被破坏。

DOI：
10.1161/circresaha.123.323276
发表时间：
2023
期刊：
Circulation research
影响因子：
20.1
作者：
DeAsis-Cruz,Josepheen;Andescavage,Nickie;Donofrio,MaryT;Vezina,Gilbert;Wessel,David;duPlessis,Adre;Limperopoulos,Catherine
通讯作者：
Limperopoulos,Catherine

Functional properties of resting state networks in healthy full-term newborns.

DOI：
10.1038/srep17755
发表时间：
2015-12-07
期刊：
Scientific reports
影响因子：
4.6
作者：
De Asis-Cruz J;Bouyssi-Kobar M;Evangelou I;Vezina G;Limperopoulos C
通讯作者：
Limperopoulos C

Robust motion correction and outlier rejection of in vivo functional MR images of the fetal brain and placenta during maternal hyperoxia.

母体高氧期间胎儿大脑和胎盘的体内功能性 MR 图像的稳健运动校正和异常值排斥。

DOI：
10.1117/12.2082451
发表时间：
2015
期刊：
Proceedings of SPIE--the International Society for Optical Engineering
影响因子：
0
作者：
You,Wonsang;Serag,Ahmed;Evangelou,IordanisE;Andescavage,Nickie;Limperopoulos,Catherine
通讯作者：
Limperopoulos,Catherine

Maternal psychological distress during the COVID-19 pandemic and structural changes of the human fetal brain.

DOI：
10.1038/s43856-022-00111-w
发表时间：
2022
期刊：
COMMUNICATIONS MEDICINE
影响因子：
0
作者：
Lu, Yuan-Chiao;Andescavage, Nickie;Wu, Yao;Kapse, Kushal;Andersen, Nicole R.;Quistorff, Jessica;Saeed, Haleema;Lopez, Catherine;Henderson, Diedtra;Barnett, Scott D.;Vezina, Gilbert;Wessel, David;du Plessis, Adre;Limperopoulos, Catherine
通讯作者：
Limperopoulos, Catherine

In infants with congenital heart disease autonomic dysfunction is associated with pre-operative brain injury.

DOI：
10.1038/s41390-021-01931-7
发表时间：
2022-06
期刊：
PEDIATRIC RESEARCH
影响因子：
3.6
作者：
Schlatterer, Sarah D.;Govindan, Rathinaswamy B.;Murnick, Jonathan;Barnett, Scott D.;Lopez, Catherine;Donofrio, Mary T.;Mulkey, Sarah B.;Limperopoulos, Catherine;du Plessis, Adre J.
通讯作者：
du Plessis, Adre J.