Brain Structure and Function in Adolescents after the Fontan Operation

单心室病变占所有先天性心脏病（CHD）的10-15%，但占CHD的25 保健资源。单心室患者的生存率显著改善， 在Fontan手术（“Fontan患者”）中达到高潮的姑息治疗，揭示了这一人群具有 神经系统和发育异常患病率高。此外，现在Fontan后的大多数患者 存活到成年，当神经发育障碍的后果可能影响就业能力时， 心理健康我们建议评估155例13 - 17岁的Fontan患者， 年龄和性别相似的一般人群中的青少年。在目标1中，Fontan和对照组将 通过磁共振成像（MRI）测量大脑结构进行比较。使用定量 体积MRI成像，主要结果将是总皮质灰质的分割体积。 次要结局将包括其他分段体积：皮质和皮质下灰质，白色 脑灰质、脑脊液（CSF）、颅内总体积（皮质灰质+皮质下灰质+ 白色物质+ CSF）和包裹的局部脑体积。使用扩散张量MRI成像， 结果将是区域性白色物质微结构，如通过分数各向异性测量的。二次 结果将是区域表观扩散系数。目标2将比较Fontan和对照品 MRI测量大脑功能。执行功能和视觉空间的主要结果 功能将是区域功能性MRI（fMRI）激活来自Stroop范式和 视觉闭合范例。目的3将评价脑MRI测量与 学习成绩、认知和行为。主要神经认知结局将是总体 韦克斯勒个人成就测验II的综合得分。次要结果将包括测量 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 功能，以及具体的精神病诊断，包括情绪，焦虑，注意力缺陷/破坏性 行为和精神障碍目的4探讨脑MRI测量值与遗传因素的关系 和医疗因素。Fontan患者将由临床遗传学家进行评估， 微阵列，并有机会为DNA生物储存库提供样品。我们将使用相关性和 回归方法分析MRI测量与遗传和医学因素的关联。我们将 探讨这些因素是否通过相互作用改变MRI结果与认知之间的关系 模型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的神经发育后遗症。

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.