Super-resolution imaging of brain microvascular changes in a model of Alzheimer Disease

阿尔茨海默病模型脑微血管变化的超分辨率成像

• 批准号: 10430929
• 负责人: DANIEL A LLANO
• 金额: $ 42.15万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10430929
• 关键词: Aerobic Exercise; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease model; Alzheimer' s disease pathology; Alzheimer' s disease risk; Anatomy; Animal Disease Models; Animals; Area; Automobile Driving; Autopsy; Behavior; Biological; Blood; Blood Vessels; Blood Volume; Blood capillaries; Blood flow; Brain; Brain Diseases; Brain imaging; Brain region; Cerebrovascular Circulation; Cerebrovascular system; Chronic; Cognition; Cognitive; Communities; Coupled; Data; Development; Diabetes Mellitus; Disease; Exercise; Functional Imaging; Goals; Hippocampus (Brain); Human; Hypertension; Illness impact; Image; Imaging Device; Imaging Techniques; Impaired cognition; Individual; Intervention; Life; Longevity; Measures; Microscopy; Mus; Nerve Degeneration; Obesity; Pathogenesis; Penetration; Physical Exercise; Physiology; Population; Public Health; Research; Resolution; Rest; Risk Factors; Science; Societies; Speed; Structure; Techniques; Therapeutic Intervention; Time; Tissue imaging; Tissues; Work; abeta deposition; age group; age related; aging population; angiogenesis; base; cardiovascular risk factor; cerebral microvasculature; cognitive change; cognitive function; effective therapy; high risk; histological studies; imaging approach; imaging study; microvascular pathology; middle age; millimeter; mouse model; novel; novel imaging technique; preservation; ultrasound; vascular risk factor

Project Summary Although biomedical science has made remarkable progress in extending the human lifespan, this lengthening of life has not necessarily been matched by longevity in cognition. Older individuals are at significantly higher risk for developing Alzheimer Disease (AD). Thus, the rising numbers of older individuals, coupled with aging-related risk for AD, is rapidly becoming a public health crisis. It is therefore important that we understand the mechanisms underlying declining cognitive function in AD. Although many mechanisms underlying cognitive decline in AD have been proposed, two universal findings motivate the current work: 1) vascular risk factors are a strong predictor of AD and 2) histopathological studies have shown profound alterations in the microvasculature of the AD brain. Although these studies point to vascular compromise as a potential contributory agent of AD-associated cognitive decline, there are currently no techniques available that permit a detailed assessment of the cerebral microvasculature of deep and superficial blood vessels in a living animal. Thus, it has not been possible to track vascular changes over time or to determine the impact of therapeutic interventions on the cerebral microvasculature. To this end, our team has been developing a novel form of super- resolution vascular imaging known as ultrasound localization microscopy (ULM). ULM can image micron-size blood vessels many millimeters deep into the brain, and can capture dynamics of blood flow (speed, flow uniformity and direction) which are not available using histological studies. Here, we propose to use ULM to investigate AD-related changes in blood flow dynamics and will relate them to AD-related changes in behavior in a mouse model of AD. In addition, we will determine if an intervention known to mitigate AD-related cognitive changes – aerobic exercise – restores regional cerebral microvasculature dynamics in AD model animals. Successful completion of this work will not only unveil previously poorly understood changes in microvascular dynamics with AD, but will also advance a novel imaging technique with broad potential applications to understand many other disorders of the brain.

项目摘要 尽管生物医学科学在延长人类寿命方面取得了显着进步，但 这种延长的延长不一定与认知中的寿命相匹配。年龄较大 个体患阿尔茨海默氏病（AD）的风险明显更高。那，复活 老年人的数量以及与衰老相关的AD风险的数量正在迅速成为公众 健康危机。因此，重要的是要了解下降的机制 AD中的认知功能。尽管广告认知能力下降的许多机制具有 已提出，两个普遍的发现激发了当前的工作：1）血管风险因素是一个 AD和2）组织病理学研究的强烈预测指标显示了 广告大脑的微脉管系统。尽管这些研究表明血管妥协是 广告相关认知能力下降的潜在贡献者，目前尚无技术 可用的可用可详细评估深处的脑微脉管系统 活动物中的浅表血管。那是不可能追踪血管的 随着时间的推移变化或确定热干预对 脑微脉管系统。为此，我们的团队一直在开发一种新颖的超级形式 分辨率的血管成像被称为超声定位显微镜（ULM）。乌尔姆可以形象 微米大小的血管许多毫米深入大脑，可以捕获 血流（速度，流量均匀性和方向），使用组织学研究无法获得。 在这里，我们建议使用ULM研究血流动态的广告相关变化，并将 将它们与AD鼠标模型中的AD相关行为变化相关联。此外，我们将 确定是否已知的干预措施减轻与广告相关的认知变化 - 有氧运动 - 恢复AD模型动物中的区域脑微脉管动力学。成功的 这项工作的完成不仅会公布以前不了解微血管的变化 AD动力学，但也将推进具有广泛潜力的新型成像技术 了解大脑的许多其他疾病的应用。