MINDS Imaging Ancillary Study

先天性心脏病(CHD)治疗的巨大进步提高了存活率 成人率从上世纪60年代S的10%上升到现在的近90%。随着人口结构的变化，成人冠心病 (Achd)患者的数量现在超过了儿科CHD患者。1 ACHD患者表现出领域特异性 神经认知缺陷，如执行功能障碍，与生活质量下降有关 包括教育程度和社会互动方面的缺陷。2-7这些缺陷与风险因素有关 这可能发生在整个生命周期，包括遗传异常，累积的缺氧/缺血损伤，以及， 成人发病的动脉粥样硬化性脑血管疾病。我们的主要假设是ACHD患者 表现出血管性脑损伤和结构性/生理性脑改变，可预测特发性脑损伤 神经认知缺陷，包括执行功能障碍，可由行为和环境改变 CR的丰富指标(例如，教育水平和生活方式/社会习惯)。我们建议进行一项辅助研究，以 NHLBI资助的儿科心脏网络(PHN)“多机构神经认知发现研究(Minds) 成人先天性心脏病(ACHD)。我们将利用Minds-ACHD家长研究数据(即NIH 工具箱神经心理学电池/临床数据/生物样本)和我们已建立的神经成像 协调，我们目前用于PHN单脑室重建(SVRIII)多中心脑 Connectome研究(R01-HL128818；PI-Panigrahy)，以测量ACHD患者的神经成像生物标志物 相同的PHN站点。我们的具体目标是：具体目标1(脑损伤)：确定是否与血管相关 脑损伤(皮质梗塞、含铁血黄素损害和白质高信号)与特定的 ACHD患者的神经认知缺陷(如NIH工具箱总分)。特定目标2(大脑 结构)：确定额颞叶皮质厚度和白质连接性是否降低 与ACHD的特定神经认知缺陷(例如，NIH工具箱正面执行亚分)相关 病人。具体目标#3(脑生理学)：确定脑血管储备减少(区域性) 脑血流/静息BOLD成像)与特定的神经认知缺陷相关(例如，NIH工具箱 ACHD患者的结晶综合评分)。具体目标#4(认知储备)：确定 神经影像生物标记物与ACHD患者神经认知结果的关系被修改 通过使用传统统计模型和机器对CR的行为和环境进行富集化 学习技巧。鉴于ACHD多模式神经影像研究的匮乏，我们建议的研究 通过提供对潜在机制的洞察，解决ACHD人群中的主要知识缺口 神经认知功能受损。我们的研究将提供神经认知的结构-生理关联 结果，这是第一个在ACHD中进行的多中心神经影像研究。重要的是，其他 行为和环境丰富数据将与这些神经成像和神经认知相结合 为认知储备建模的结果数据。这项研究的结果将有助于塑造ACHD的护理 进一步加深了我们对脑损伤和认知储备之间相互作用的理解。这个 因此，通过利用NHLBI-PHN基础设施，拟议的辅助研究既可行又具有成本效益 因此，拟议的研究与NHLBI的战略愿景很好地结合在一起。

Dramatic advances in management of congenital heart disease (CHD) have improved survival to adulthood from <10% in the 1960's to nearly 90% in the current era. With this shifting demographic, adult CHD (ACHD) patients now outnumber pediatric CHD patients.1 ACHD patients demonstrate domain-specific neurocognitive deficits such as impairment in executive function, associated with reduced quality of life that includes deficits in educational attainment and social interaction.2-7 These deficits are related to risk factors that can occur across the lifespan, including genetic abnormalities, cumulative hypoxic/ischemic injury, and, adult-onset atherosclerotic cerebrovascular disease. Our overarching hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits, including executive dysfunction, which are modified by behavioral and environmental enrichment proxies of CR (e.g., level of education and lifestyle/social habits). We propose an ancillary study to the NHLBI-funded Pediatric Heart Network (PHN) “Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD).” We will leverage the MINDS-ACHD parent study data (i.e., NIH Toolbox neuropsychological battery/clinical data/biological samples) and our established neuroimaging harmonization, which we currently use for the PHN Single Ventricle Reconstruction (SVRIII) multi-center brain connectome study (R01-HL128818; PI-Panigrahy), to measure neuroimaging biomarkers in ACHD patients at the same PHN sites. Our specific aims are: Specific Aim #1 (brain injury): To determine if vascular-related brain injury (cortical infarcts, hemosiderin lesions, and white matter hyperintensity) is associated with specific neurocognitive deficits (e.g. NIH Toolbox total composite score) in ACHD patients. Specific Aim #2 (brain structure): To determine if reduced fronto-temporal cortical thickness and white matter connectivity are associated with specific neurocognitive deficits (e.g. NIH Toolbox frontal executive sub-score) in ACHD patients. Specific Aim #3 (brain physiology): To determine if reduced cerebrovascular reserve (regional cerebral blood flow/ resting BOLD imaging) is associated with specific neurocognitive deficits (e.g. NIH Toolbox crystallized composite score) in ACHD patients. Specific Aim #4 (cognitive reserve): To determine if the associations between neuroimaging biomarkers and neurocognitive outcomes in ACHD patients are modified by behavioral and environmental enrichment proxies of CR, using traditional statistical models and machine learning techniques. Given the paucity of multi-modal neuroimaging studies in ACHD, our proposed study addresses a major knowledge gap in the ACHD population by providing insight into the mechanism underlying impaired neurocognitive outcomes. Our study will provide structural-physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging study to be performed in ACHD. Importantly, other behavioral and environmental enrichment data will be integrated with these neuroimaging and neurocognitive outcome data to model cognitive reserve. Results from this research will help shape the care of ACHD patients, and further our understanding of the interplay between brain injury and cognitive reserve. The proposed ancillary study is thus both feasible and cost-effective by leveraging the NHLBI-PHN infrastructure As such, the proposed research is well aligned with the NHLBI's Strategic Vision.