Quantitative Magnetic Resonance Properties of Cerebrospinal Fluid and Brain Health Outcomes in Pediatric Congenital Heart Disease

小儿先天性心脏病脑脊液的定量磁共振特性与脑健康结果

• 批准号: 10701753
• 负责人: Vincent Kyu Lee
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701753
• 关键词: Adolescent; Adult; Age; Blood Vessels; Brain; Cerebellum; Cerebrospinal Fluid; Characteristics; Child; Childhood; Circulation; Cognitive; Cognitive deficits; Congenital Heart Defects; Cyanosis; Dementia; Department of Defense; Detection; Development; Diagnosis; Disease; Early Diagnosis; Early Intervention; Education; Elderly; Environment; Executive Dysfunction; Exhibits; Face; Funding; General Population; Goals; Growth; Heart Abnormalities; Hippocampus; Human; Hypoxia; Image; Imaging Techniques; Impaired cognition; Impairment; Individual; Inflammatory; Intraventricular; Language; Lead; Link; Live Birth; Magnetic Resonance; Magnetic Resonance Imaging; Maintenance; Measurement; Measures; Memory; Multimodal Imaging; Neurobiology; Neurodevelopmental Deficit; Neurons; Neuropsychological Tests; Nutrient; Operative Surgical Procedures; Outcome; Participant; Patients; Pediatric Hospitals; Phase; Play; Production; Property; Proteins; Quality of life; Risk Factors; Role; Severities; Shapes; Signal Transduction; Site; Social Interaction; Structure; Subarachnoid Space; Survival Rate; System; T2 weighted imaging; Techniques; Testing; Thick; Third ventricle structure; United States; United States National Institutes of Health; Variant; autism spectrum disorder; brain health; brain parenchyma; cerebrospinal fluid flow; cognitive task; cognitive testing; congenital heart disorder; executive function; imaging biomarker; improved; in vivo; lateral ventricle; multimodality; nervous system disorder; neurodevelopment; neuronal growth; older patient; olfactory bulb; pediatric patients; peer; prognostication; wasting

Project Summary/Abstract Children with congenital heart disease (CHD) are more likely to develop neurodevelopmental deficits than the general population. Due to advances in interventional surgical techniques, survival rates for patients with CHD are high, but they face adverse neurodevelopmental challenges – such as cognitive deficits – and attain lower education and social interaction, leading to reduced quality of life. Despite a multitude of studies examining risk factors for adverse neurodevelopment outcomes in children with CHD, only a small proportion of observed variations in cognitive tests can be attributed to these tested exposures. A larger portion of risk factors that may play critical roles in adverse neurodevelopmental outcomes in children with CHD remains to be discovered. One such risk factor is likely to be alterations in cerebrospinal fluid (CSF) characteristics manifested as alterations in volume and flow dynamics. Recent studies show that normal CSF circulation is necessary for healthy neuronal growth and maintenance of a homeostatic environment for normal neuronal function. Abnormalities in the CSF have been linked to neurological diseases such as autism spectrum disorder in children and dementia in adults. In CHD, abnormal CSF findings, especially increased CSF volume, are frequently observed. Increased CSF volume has been shown to be correlated with brain dysmaturation and poor neurodevelopmental outcomes in young children with CHD. Although in the elderly, there are studies that link decreased CSF flow velocities with cognitive impairment. Currently, CSF flow alterations in children with CHD have yet to be examined in vivo, and the possible link between CSF flow and increased volume to cognitive outcomes remains to be explored. This project aims to examine the relationship between disruption in CSF characteristics and neurodevelopmental deficits in children with CHD. We hypothesize that aberrant CSF characteristics (increased volumes and decreased flow velocity) measured using MRI will be powerful multi-modal imaging predictors for neurodevelopmental outcomes in children with CHD. This project leverages a Department of Defense-funded ongoing study at UPMC Children’s Hospital of Pittsburgh involving children with CHD and age-matched healthy controls who receive MRI imaging as well as neuropsychologic testing – including executive function. In this project, we propose measuring intracranial CSF volume (extra-axial and intra-ventricular volume) using structural MRI (T1 and T2 images) and measuring CSF flow velocity through the Aqueduct Silvius using phase-contrast MRI. These CSF measurements will then be correlated with neuropsychological tests assessing executive function. The results from this proposed project will help determine (1) differences in CSF characteristics between children with CHD and healthy controls and (2) any correlation between CSF characteristics and neurodevelopmental outcomes in CHD. Taken together, we hope to develop useful CSF-based imaging biomarkers to prognosticate poor neurodevelopmental outcomes in pediatric patients with CHD.

项目总结/摘要 患有先天性心脏病（CHD）的儿童比患有先天性心脏病（CHD）的儿童更容易出现神经发育缺陷。 一般人口。由于介入手术技术的进步，冠心病患者的生存率 高，但他们面临着不利的神经发育挑战-如认知缺陷-并达到较低 教育和社会互动，导致生活质量下降。尽管有大量的研究检查风险 CHD儿童神经发育不良结局的因素，仅观察到一小部分 认知测试中的差异可归因于这些测试的暴露。更大部分的风险因素可能 在CHD儿童的不良神经发育结果中起关键作用仍有待发现。一 这种危险因素可能是脑脊液（CSF）特征的改变，表现为 体积和流动动力学。最近的研究表明，正常的CSF循环对于健康的神经元是必要的。 生长和维持正常神经元功能的稳态环境。脑脊液中的abbovine 与神经系统疾病有关，如儿童自闭症和成人痴呆症。 在CHD中，经常观察到异常CSF结果，特别是CSF体积增加。CSF增加 已经证明，在儿童中，体积与脑发育不良和神经发育不良结果相关。 幼儿CHD尽管在老年人中，有研究表明CSF流速降低与 认知障碍目前，CHD儿童的CSF流量变化尚未在体内进行检查， CSF流量和容量增加与认知结果之间的可能联系仍有待探索。这 该项目旨在研究CSF特征破坏与神经发育之间的关系， 先心病儿童的缺陷。我们假设异常的CSF特征（体积增加和 使用MRI测量的血流速度降低）将是以下疾病的有力多模态成像预测因子： CHD儿童的神经发育结局。该项目利用国防部资助的 匹兹堡UPMC儿童医院正在进行的一项研究，涉及CHD儿童和年龄匹配的健康儿童。 对照组接受MRI成像以及神经心理学测试-包括执行功能。在这 项目，我们建议使用结构测量颅内CSF体积（轴外和脑室内体积） MRI（T1和T2图像）和使用相位对比测量通过Silvius水道的CSF流速 核磁共振这些CSF测量结果将与神经心理学测试相关联， 功能本项目的结果将有助于确定（1）CSF特征的差异 CHD儿童与健康对照之间的关系，以及（2）CSF特征与 CHD的神经发育结局。综上所述，我们希望开发有用的基于CSF的成像 生物标志物，以说明儿童CHD患者神经发育不良的结果。