Brain Structure and Function in Adolescents after the Fontan Operation

Fontan 手术后青少年的大脑结构和功能

• 批准号: 8099758
• 负责人: Jane W. Newburger
• 金额: $ 75.51万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8099758
• 关键词: Academic achievement; Achievement; Address; Adolescent; Adult; Affect; Age; Anisotropy; Anxiety; Attention; Behavior; Behavior Disorders; Behavioral; Brain; Cardiac; Cerebrospinal Fluid; Cerebrum; Characteristics; Child; Clinical; Cognition; Cognitive; Common Ventricle; Congenital Abnormality; Control Groups; DNA; Development; Diffuse; Diffusion; Emotional; Employee Strikes; Fontan Procedure; Functional Magnetic Resonance Imaging; Gender; General Population; Genetic; Health; Health Status; Healthcare; High Prevalence; Image; Individual; Inferior; Intelligence; Intervention; Language; Lateral; Learning; Learning Disabilities; Lesion; Lobule; Magnetic Resonance Imaging; Maps; Measures; Medical; Medical Genetics; Medical History; Memory; Mental Health; Methods; Modeling; Molecular Abnormality; Moods; Motor; Nature; Neuraxis; Neurocognition; Neurocognitive; Neurodevelopmental Impairment; Neurologic; Outcome; Parietal; Patients; Performance; Phenotype; Population; Prefrontal Cortex; Psyche structure; Psychiatric Diagnosis; Psychotic Disorders; Quality of life; Resources; Risk Factors; Sampling; Social Class; Specificity; Staging; Structure; Syndrome; Testing; Visual; Visuospatial; base; biobank; brain volume; congenital heart disorder; design; developmental disease; executive function; gray matter; high risk; improved; nervous system disorder; neurodevelopment; neuropsychological; palliation; primary outcome; secondary outcome; sex; social skills; success; white matter

DESCRIPTION (provided by applicant): Single ventricle lesions comprise 10-15% of all congenital heart disease (CHD), but consume 25% of CHD health care resources. Striking improvement in the survival of patients with single ventricle, treated with staged palliation culminating in the Fontan operation ("Fontan patients"), has revealed that this population harbors a high prevalence of neurologic and developmental abnormalities. Furthermore, most patients after Fontan now survive to adulthood, when consequences of neurodevelopmental impairment may affect employability and mental health. We propose to evaluate 155 Fontan patients at ages 13 through 17 years, compared to 50 adolescents in the general population of similar age and gender. In Aim 1, Fontan and control groups will be compared on Magnetic Resonance Imaging (MRI) measures of brain structure. Using quantitative volumetric MRI imaging, the primary outcome will be the segmented volume of total cortical gray matter. Secondary outcomes will comprise other segmented volumes: cortical and subcortical gray matter, white matter, cerebrospinal fluid (CSF), total intracranial volume (cortical gray matter + subcortical gray matter + white matter + CSF), and parcellated regional brain volumes. Using diffusion tensor MRI imaging, the primary outcome will be regional white matter microstructure, as measured by fractional anisotropy. Secondary outcomes will be regional apparent diffusion coefficients. Aim 2 will compare the Fontan and control groups on MRI measures of brain function. The primary outcomes for executive function and visual-spatial function will be regional functional MRI (fMRI) activation derived from performance of a Stroop paradigm and a visual closure paradigm, respectively. Aim 3 will evaluate the relationship of brain MRI measures to academic achievement, cognition, and behavior. The primary neurocognitive outcome will be the Total Composite score on the Wechsler Individual Achievement Test-II. Secondary outcomes will include measures of ability (IQ), learning disability, neuropsychological function (i.e., language, memory, attention, executive functions, and visual-spatial/motor integration), and mental health, including quality-of-life and global emotional functioning, as well as specific psychiatric diagnoses including mood, anxiety, attention-deficit/disruptive behavior, and psychotic disorders. Aim 4 will explore the relationship of brain MRI measures to genetic and medical factors. Fontan patients will be assessed by a clinical geneticist, undergo chromosomal microarray, and have the opportunity to provide a sample for a DNA biorepository. We will use correlation and regression methods to analyze associations of MRI measures with genetic and medical factors. We will explore whether these factors modify the relationship between MRI findings and cognition through interaction models. These studies will establish, with greater clarity and specificity, the nature and basis of neurodevelopmental sequelae of single ventricle patients following Fontan palliation. PUBLIC HEALTH RELEVANCE: Patients with single ventricle who have undergone the Fontan procedure have a high risk of neurologic, developmental, and behavioral disorders that are important barriers to learning and development; interfere with the acquisition of academic, vocational, and social skills; and negatively affect adult adjustment. The proposed assessment offers an opportunity to address important questions of broad biologic significance regarding the relationships of measures of brain structure and function with neurodevelopment, as well as their association with genetic and medical factors. Improved understanding of these interrelationships may facilitate the design and implementation of interventions to target specific central nervous system deficits and thereby maximize adult neuropsychological function in the growing post-Fontan population.

描述（申请人提供）：单心室病变占所有先天性心脏病 (CHD) 的 10-15%，但消耗了 25% 的 CHD 医疗资源。经过阶段性姑息治疗并最终进行 Fontan 手术（“Fontan 患者”）的单心室患者（“Fontan 患者”）的生存率显着改善，这表明该人群神经系统和发育异常的患病率很高。此外，大多数接受 Fontan 治疗的患者现在都能存活到成年，此时神经发育障碍的后果可能会影响就业能力和心理健康。我们建议对 155 名 13 岁至 17 岁的 Fontan 患者进行评估，与相似年龄和性别的一般人群中的 50 名青少年进行比较。在目标 1 中，将比较 Fontan 和对照组的大脑结构磁共振成像 (MRI) 测量结果。使用定量体积 MRI 成像，主要结果将是总皮质灰质的分段体积。次要结果将包括其他分段体积：皮质和皮质下灰质、白质、脑脊液（CSF）、颅内总体积（皮质灰质+皮质下灰质+白质+CSF）和分区脑体积。使用扩散张量 MRI 成像，主要结果将是通过分数各向异性测量的区域白质微观结构。次要结果是区域表观扩散系数。目标 2 将比较 Fontan 组和对照组的脑功能 MRI 测量结果。执行功能和视觉空间功能的主要结果将是分别源自斯特鲁普范式和视觉闭合范式表现的区域功能性 MRI (fMRI) 激活。目标 3 将评估脑部 MRI 测量与学业成绩、认知和行为的关系。主要的神经认知结果将是韦克斯勒个人成就测试 II 的综合总分。次要结果将包括能力（IQ）、学习障碍、神经心理功能（即语言、记忆、注意力、执行功能和视觉空间/运动整合）以及心理健康（包括生活质量和整体情绪）的测量功能，以及特定的精神科诊断，包括情绪、焦虑、注意力缺陷/破坏性行为和精神障碍。目标 4 将探讨脑部 MRI 测量与遗传和医学因素的关系。 Fontan 患者将由临床遗传学家进行评估，接受染色体微阵列检查，并有机会为 DNA 生物样本库提供样本。我们将使用相关和回归方法来分析 MRI 测量值与遗传和医学因素的关联。我们将通过交互模型探讨这些因素是否会改变 MRI 结果与认知之间的关系。这些研究将更加明确和具体地确定 Fontan 姑息治疗后单心室患者神经发育后遗症的性质和基础。公共卫生相关性：接受 Fontan 手术的单心室患者出现神经系统、发育和行为障碍的风险很高，这些障碍是学习和发育的重要障碍；干扰学术、职业和社交技能的获得；并对成人的适应产生负面影响。拟议的评估提供了一个机会来解决具有广泛生物学意义的重要问题，这些问题涉及大脑结构和功能测量与神经发育的关系，以及它们与遗传和医学因素的关联。对这些相互关系的更好的理解可能有助于针对特定中枢神经系统缺陷的干预措施的设计和实施，从而最大限度地提高不断增长的后丰坦人群的成人神经心理功能。