Cerebral Artery Integrity Linked to Brain Injury and Cognition in Congenital Heart Disease

脑动脉完整性与先天性心脏病的脑损伤和认知有关

• 批准号: 9337504
• 负责人: Rajesh Kumar
• 金额: $ 49.57万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9337504
• 关键词: 18 year old; Adolescent; Affect; Age; Alzheimer' s Disease; Area; Arteries; Blood; Blood capillaries; Brain; Brain Injuries; Brain region; Cognition; Cognitive; Cognitive deficits; Comparative Study; Congenital Abnormality; Congenital Heart Defects; Contrast Media; Data; Diabetes Mellitus; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Endothelium; Epilepsy; Gender; Hippocampus (Brain); Hypertension; Hypoxemia; Hypoxia; Image Analysis; Imaging Techniques; Impairment; Injury; Investigation; Language; Lead; Learning; Link; Low Cardiac Output; Magnetic Resonance Imaging; Measures; Memory; Meningitis; Morbidity - disease rate; Multiple Sclerosis; Operative Surgical Procedures; Outcome; Parietal; Patients; Performance; Pilot Projects; Procedures; Process; Public Health; Publishing; Quality of life; Radiation; Regional Perfusion; Reporting; Research; Research Design; Sample Size; Sampling; Schools; Site; Spin Labels; Stroke; Time; Tissues; Traumatic Brain Injury; Travel; Visuospatial; base; brain repair; brain tissue; capillary; cerebral artery; cognitive control; cognitive function; cognitive testing; congenital heart disorder; diffusion weighted; effective intervention; effective therapy; executive function; frontal lobe; high risk; high risk population; improved; inclusion criteria; indexing; mortality; nerve injury; palliation; patient population; prevent; relating to nervous system; repaired; water diffusion

PROJECT SUMMARY/ ABSTRACT Adolescents with congenital heart disease (CHD) show brain injury in regions (hippocampus, frontal cortex, temporal, and parietal), which control cognition. Abnormalities in these sites are associated with cognitive deficits. However, the underlying cause of brain injury in these areas in CHD is unclear. Alteration in cerebral artery integrity (measured by arterial transit time [ATT]), which is associated with neural injury in other diseases, is a potential cause of brain injury in CHD. However, there are no published reports of cerebral artery integrity in CHD or regarding any associations between cerebral artery integrity, brain injury, and cognition in this condition. We will use a comparative study design, 80 subjects (40 CHD / 40 Healthy controls), with inclusion criteria for CHD will be subjects between 14-18 years of age, have undergone surgical repair or palliation, and controls will be age- and gender-matched to CHD subjects. Using non-invasive brain magnetic resonance imaging (MRI) procedures, our preliminary study is the first to report abnormalities in ATT values (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures) in CHD and that these changes are associated with brain injury (as examined by diffusion tensor imaging based mean diffusivity [MD], an MRI measure of tissue integrity) in the hippocampus, frontal cortex, temporal, and parietal regions in CHD subjects compared to controls. However, while promising, the sample size in this preliminary study was quite small and did not allow us to control for important covariates, such as age and gender. Therefore, the specific aims of this proposal are to: 1) compare ATT values (calculated from diffusion-weighted pCASL) between CHD and age- and gender-matched control subjects; 2) compare regional MD values, derived from diffusion tensor imaging data and cognitive scores (measured by the total Montreal Assessment of Cognition [MoCA] and general memory index (GMI) score from the Wide Range Assessment of Memory and Learning [WRAML2]) between CHD and age- and gender-matched control subjects; 3) examine the relationships between altered ATT (indicating cerebral artery integrity), regional MD values (assessment of injury), and cognitive scores in CHD patients. In summary, CHD patients show significant brain injury in areas that control cognition. These deficits are associated with poor school performance, increased morbidity and mortality, and poorer quality of life. A potential cause of this brain injury may be compromised cerebral artery integrity; however, status of the artery integrity and its association with brain injury and cognition has not been reported in CHD. Information from this study has the potential to disclose a process contributing to brain injury in CHD. Thus, it has important implications on identification of effective treatments for CHD by repairing cerebral artery integrity as used in other conditions (such as stroke and traumatic brain injury), which could dramatically improve cognitive function, reduce mortality and morbidity, and increase quality of life in this high risk patient population.

项目摘要/摘要 先天性心脏病(CHD)青少年表现为脑部损伤(海马体、额叶 大脑皮层、颞叶和顶叶)，它们控制认知。这些部位的异常与 认知缺陷。然而，CHD患者这些区域脑损伤的潜在原因尚不清楚。更改中 脑动脉完整性(以动脉通过时间[ATT]衡量)，这与其他患者的神经损伤有关 疾病，是CHD脑损伤的潜在原因。然而，目前还没有关于脑动脉的报道。 CHD的完整性或关于脑动脉完整性、脑损伤和认知之间的任何联系 这种情况。我们将采用比较研究设计，80名受试者(40名CHD/40名健康对照)， 冠心病的纳入标准将包括年龄在14-18岁之间、接受过手术修复或 缓解，对照将与CHD受试者的年龄和性别匹配。使用非侵入性脑磁力 在磁共振成像(MRI)过程中，我们的初步研究首次报告了ATT值的异常 (通过扩散加权伪连续动脉自旋标记[pCASL]程序)治疗CHD，这些 变化与脑损伤相关(如通过基于扩散张量成像的平均扩散系数[MD]检查， 冠心病患者的海马区、额叶皮质、颞区和顶区的组织完整性的MRI测量 受试者与对照组的比较。然而，尽管前景看好，但这项初步研究的样本量相当大。 很小，不允许我们控制重要的协变量，如年龄和性别。因此，具体的 该建议的目的是：1)比较CHD和CHD之间的ATT值(根据扩散加权的pCASL计算 和年龄和性别匹配的对照受试者；2)比较由扩散张量得出的区域MD值 成像数据和认知分数(由蒙特利尔认知评估[MoCA]和 记忆和学习广度评估的一般记忆指数(GMI)得分[WRAML2]) 冠心病与年龄和性别匹配的对照组之间的关系；3)检查改变与 ATT(指示大脑动脉完整性)、区域MD值(损伤评估)和认知评分 冠心病患者。 总而言之，CHD患者在控制认知的区域表现出明显的脑损伤。这些赤字是 与学业成绩差、发病率和死亡率增加以及生活质量下降有关。一个 这种脑损伤的潜在原因可能是大脑动脉的完整性受损；然而，动脉的状态 完整性及其与脑损伤和认知的关系在CHD中尚未见报道。信息来自 这项研究有可能揭示CHD脑损伤的一个过程。因此，它具有重要的 脑动脉完整性修复术对冠心病有效治疗的意义 其他情况(如中风和创伤性脑损伤)，可以显著改善认知能力 在这一高危患者群体中，改善其功能，降低死亡率和发病率，提高生活质量。