Genetic and hemodynamic effects on prenatal cortical development in congenital heart disease
遗传和血流动力学对先天性心脏病产前皮质发育的影响
基本信息
- 批准号:10380094
- 负责人:
- 金额:$ 58.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAllelesAreaBirthBrainCardiovascular systemCerebrovascular CirculationCerebrumChildCongenital DisordersDevelopmentEarly InterventionEarly identificationElderlyFetal DevelopmentFetusFoundationsFutureGene ExpressionGenesGeneticGrowthHeartHypoplastic Left Heart SyndromeImpairmentIndividualInjuryInterventionLive BirthLungMagnetic Resonance ImagingMeasuresMethodsMonitorNeurodevelopmental DisabilityObstructionOxygenPatientsPatternPerfusionPrefrontal CortexRiskRoleSecond Pregnancy TrimesterSingle ventricle congenital heart diseaseSiteSocioeconomic StatusSurfaceTherapeutic InterventionThickThird Pregnancy TrimesterTimeTreatment EfficacyVariantVascular blood supplyaortic archbasebrain abnormalitiesbrain magnetic resonance imagingbrain volumecerebral hemodynamicscognitive functioncohortcongenital heart disorderexome sequencingfetalfrontal lobegenetic varianthemodynamicshigh riskhypoperfusionimaging biomarkerimaging studyin uteroinsightlarge datasetsneonatal periodneurogenesisprenatalprospectiveresiliencesexsuccess
项目摘要
PROJECT SUMMARY/ABSTRACT
Congenital heart disease (CHD) is one of the most common congenital disorders, affecting about 1% of all live
births. More than half of children with moderate or severe CHD have neurodevelopmental disabilities (NDD)
that persist into later life. Quantitative methods that can objectively identify subjects at high risk for NDD as
early as possible are needed to allow for characterization of the mechanisms underlying NDD and monitor the
success of potential therapeutic interventions. Brain magnetic resonance imaging (MRI) studies provide
evidence for a prenatal origin of NDD by detecting reduced global brain volumes and gyrification in fetuses with
CHD. However, these whole-brain measures do not provide insight into regional brain vulnerabilities or second
trimester differences in brain development. In addition, no studies have yet explored the potential role of
genetic variants and attempted to disentangle the relative contributions of genetic and hemodynamic factors on
prenatal brain development in CHD. Since patients with single-ventricle (SV) CHD suffer high rates of NDD
and show both severe in utero reduction in oxygenated cerebral blood supply and frequent damaging genetic
variants, fetal SV CHD cohort is an ideal group in which to explore markers of altered early brain development
influenced by genetic and/or cerebral hemodynamic factors. This study will examine sulcal patterns and
regional cortical growth (thickness and surface area) to indicate the effects of genetic variants and altered
cerebral hemodynamics respectively using a large dataset of retrospective and prospective longitudinal MRIs
from the second trimester to birth with three time points in 175 SV CHD and 260 typically developing (TD)
subjects. Sulcal pattern development will be compared between SV CHD and TD subjects and correlated with
rare damaging variants in high heart expression (HHE) genes and presence of neuroprotective APOE allele in
SV CHD. We will also develop surface-based regional analysis of fetal cortical thickness and surface area.
Regional cortical thickness and surface area will be compared between SV CHD and TD subjects and
correlated with different types of cerebral blood flow in SV CHD. We hypothesize that sulcal pattern alterations
will be detected in SV CHD in the second trimester and more abnormal in SV CHD subjects with rare
damaging variants in HHE and/or neuroresilience APOE genes. Differences in cortical thickness and surface
area between SV CHD and TD subjects may be regionally inhomogeneous and more severe in the frontal
regions. Regional cortical growth will be more reduced in SV CHD subjects with aortic outflow obstruction and
retrograde aortic arch flow compared to the subjects with pulmonary obstruction with anterograde arch flow or
unobstructed outflow tracts. This project would allow early identification of the relative roles of altered genetics
and cerebral perfusion and lay the foundation for early selection and optimization of individual therapy and
deciding the efficacy of the interventions in CHD.
项目摘要/摘要
先天性心脏病(CHD)是最常见的先天性疾病之一,约1%的人患有先天性心脏病
出生。超过一半的中重度CHD儿童有神经发育障碍(NDD)
会一直持续到以后的生活。可以客观地识别新城疫高危人群的定量方法
需要尽早确定NDD基础机制的特征,并监测
潜在治疗干预的成功。脑磁共振成像(MRI)研究提供了
通过检测患有新城疫的胎儿整体脑体积减少和脑回变来证明NDD的产前起源
先心病。然而,这些全脑测量并不能提供对区域大脑脆弱性的洞察或第二
大脑发育的三个月的差异。此外,目前还没有研究探索这种物质的潜在作用。
并试图解开遗传因素和血流动力学因素对
先天性心脏病的产前脑发育。由于单心室(SV)冠心病患者的NDD发生率较高
并显示出宫内氧合脑供血严重减少和频繁的遗传损伤
变异的胎儿SV CHD队列是探索早期脑发育改变标志物的理想群体
受遗传和/或脑血流动力学因素的影响。这项研究将检查脑沟的模式和
区域皮质生长(厚度和表面积)指示遗传变异和改变的影响
分别使用回顾性和前瞻性纵向磁共振成像的大数据集进行脑血流动力学研究
从怀孕中期到出生,175例先天性心脏病和260例典型发育中的三个时间点(TD)
研究对象。将比较SV CHD和TD受试者的唇型发育,并与
心脏高表达基因的罕见破坏性变异和神经保护性载脂蛋白E等位基因的存在
SV CHD我们还将开发基于表面的胎儿皮质厚度和表面积的区域分析。
将比较SV、CHD和TD受试者的区域皮质厚度和表面积
与SV CHD的不同脑血流类型相关。我们假设脑沟模式的改变
在妊娠中期会在SV CHD中检测到,而在SV CHD患者中更多的是罕见的异常
HHE和/或神经韧性APOE基因的破坏性变异。皮质厚度和表面积的差异
先天性心脏病和先天性心脏病患者之间的面积可能在区域上不均匀,额叶更严重。
地区。合并主动脉流出道梗阻的先天性心脏病患者的局部皮质生长将更加减少。
主动脉弓逆行血流与肺梗阻伴顺行动脉弓血流的比较
流出通道畅通无阻。该项目将使我们能够及早确定基因改变的相对作用。
和脑血流灌注,为早期选择和优化个体化治疗奠定基础
决定冠心病干预措施的疗效。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Kiho Im其他文献
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{{ truncateString('Kiho Im', 18)}}的其他基金
Measuring cortical plate and subplate thickness in the human fetal brain from magnetic resonance images
从磁共振图像测量人类胎儿大脑的皮质板和亚板厚度
- 批准号:
10493288 - 财政年份:2021
- 资助金额:
$ 58.59万 - 项目类别:
Measuring cortical plate and subplate thickness in the human fetal brain from magnetic resonance images
从磁共振图像测量人类胎儿大脑的皮质板和亚板厚度
- 批准号:
10366327 - 财政年份:2021
- 资助金额:
$ 58.59万 - 项目类别:
Genetic and hemodynamic effects on prenatal cortical development in congenital heart disease
遗传和血流动力学对先天性心脏病产前皮质发育的影响
- 批准号:
10594404 - 财政年份:2020
- 资助金额:
$ 58.59万 - 项目类别:
Genetic and hemodynamic effects on prenatal cortical development in congenital heart disease
遗传和血流动力学对先天性心脏病产前皮质发育的影响
- 批准号:
10197244 - 财政年份:2020
- 资助金额:
$ 58.59万 - 项目类别:
Spatio-temporal Patterns of Early Cortical Folding in the Human Fetal Brain
人类胎儿大脑早期皮质折叠的时空模式
- 批准号:
9188564 - 财政年份:2015
- 资助金额:
$ 58.59万 - 项目类别:
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