Structural and diffusion changes of perivascular space in aging, cognitive decline and Alzheimer's disease

衰老、认知能力下降和阿尔茨海默病中血管周围空间的结构和扩散变化

• 批准号: 10302009
• 负责人: Jeiran Choupan
• 金额: $ 82.36万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-05 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10302009
• 关键词: Address; Affect; Age; Aging; Agreement; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease risk; American; Amyloid beta-Protein; Anatomy; Animals; Area; Astrocytes; Basal Ganglia; Biological; Blood - brain barrier anatomy; Blood Vessels; Blood capillaries; Brain; Cerebrospinal Fluid; Characteristics; Clinical; Clinical Research; Cognitive; Computational Technique; Data; Databases; Dementia; Deposition; Diabetes Mellitus; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Drainage procedure; Early Diagnosis; Fibrinogen; Fostering; Functional disorder; Funding; Goals; Human; Hypertension; Image; Image Analysis; Imaging Device; Impaired cognition; Impairment; Individual; Intercellular Fluid; Knowledge; Liquid substance; Lymphatic; Lymphatic System; Magnetic Resonance Imaging; Maps; Measurement; Metabolic; Microvascular Dysfunction; Mission; Modality; Modeling; Monitor; Morphology; Neurodegenerative Disorders; Neurofibrillary Tangles; Neuroglia; Outcome; Outcome Measure; Pathogenesis; Pathologic; Pathology; Pathway interactions; Patients; Physiological; Population; Property; Proteins; Public Health; Radiology Specialty; Research; Research Personnel; Resolution; Resources; Risk Factors; Role; Senile Plaques; Structure; Techniques; Testing; Time; Tissues; United States National Institutes of Health; Variant; Visual; Work; abeta deposition; age related; aging brain; aquaporin 4; arteriole; base; biophysical properties; brain health; cardiovascular risk factor; cohort; computational suite; connectome; healthy aging; human data; hyperphosphorylated tau; improved; in vivo; innovation; insight; interest; nervous system disorder; neuroimaging; neurovascular; normal aging; secondary analysis; tau Proteins; tool; uptake; vascular cognitive impairment and dementia; vascular risk factor; venule; wasting

PROJECT SUMMARY Perivascular spaces (PVS) are the area around arterioles, venules and capillaries which accommodate the clearance of the metabolic waste via Aquaporin-4 channels expressed on astrocytic endfeet and are involved in blood-brain barrier transport. PVS have come to prominence recently through potential roles in brain interstitial fluid drainage and waste clearance, and in the pathogenesis of Alzheimer’s disease (AD) and other neurodegenerative disorders. While animal studies have precisely clarified this mechanism, data from humans are relatively crude and limited to visual counting of visible PVS on clinical magnetic resonance images, and this limits our understands of the morphology, biophysical properties and distribution of the PVS in human aging and AD. The long-term goal is to understand the role of PVS in brain health and the degree to which it alters in AD. The objective of this project is to map morphologic and diffusion characteristics of the PVS fluid in healthy aging, and how it is altered in the early stages of AD. The central hypothesis is that imaging-derived PVS fluid characteristics, such as volume occupied and diffusion properties, are differentially and selectively altered in cognitive decline and AD in comparison with normal aging. The rationale underlying this proposal is that in vivo noninvasive mapping of the PVS provides mechanistic insight about AD pathophysiology. The proposed work will also develop widely applicable open resources to map PVS morphologic and diffusion properties that can be applied to a wide range of neurological disorders. The central hypothesis will be tested by pursuing three specific aims: 1) Characterize changes in PVS fluid in normal aging individuals with no cognitive decline nor evidence of AD pathology and evaluate the effect of image acquisition strategy on outcome measures; 2) Identify PVS alteration in cognitive decline and in individuals with AD pathology; and 3) Determine the extent to which PVS is associated with cardiovascular risk factors versus AD pathology. We will pursue these aims by applying innovative MRI-based computational techniques on recently available data of normal aging and patients with cognitive decline from multiple large NIH-funded studies. Computational techniques include both recently developed neuroimaging techniques sensitized to the PVS and more established structural image analysis techniques. The proposed research is significant, because it will aid in the understanding of AD pathophysiological mechanisms and consequently assist in the early diagnosis and disease monitoring of AD. It is also significant because it will make public resources available that can be used to study other neurological disorders characterized by impaired PVS in the brain. The results will have an important positive impact immediately because they will identify and map, for the first time, PVS alteration in human brain across aging, cognitively impaired and AD individuals. Our shared PVS imaging tools can also be more broadly applied to a wide range of clinical and research applications by other groups as well.

项目概要 血管周围空间 (PVS) 是小动脉、小静脉和毛细血管周围的区域，可容纳 通过星形胶质细胞端脚上表达的 Aquaporin-4 通道清除代谢废物，并参与 PVS 最近因在脑间质中的潜在作用而受到重视。 液体引流和废物清除，以及阿尔茨海默病 (AD) 和其他疾病的发病机制 虽然动物研究已经精确阐明了这一机制，但来自人类的数据 相对粗糙并且仅限于临床磁共振图像上可见 PVS 的目视计数，并且这 限制了我们对人类衰老过程中PVS的形态、生物物理特性和分布的理解 AD。长期目标是了解 PVS 在大脑健康中的作用以及它在 AD 中的改变程度。 该项目的目标是绘制 PVS 流体的形态和扩散特征图 健康衰老，以及 AD 早期阶段如何改变 核心假设是成像衍生的。 PVS 流体特性（例如体积占用和扩散特性）是有差别且有选择性的 与正常衰老相比，认知能力下降和 AD 发生了变化。 PVS 的体内无创绘图提供了有关 AD 病理生理学的机制见解。 拟议的工作还将开发广泛适用的开放资源来绘制 PVS 形态和扩散图 可应用于广泛的神经系统疾病的特性将通过以下方法进行检验。 追求三个具体目标：1）描述无认知功能的正常衰老个体的 PVS 液体变化特征 AD 病理学的衰退或证据并评估图像采集策略对结果的影响 措施；2) 识别认知衰退和 AD 病理个体的 PVS 改变；以及 3) 确定 PVS 与心血管危险因素和 AD 病理学的相关程度我们将进行研究。 目标是通过基于 MRI 的创新应用计算技术来处理最近可用的正常衰老数据和 NIH 资助的多项大型研究显示认知能力下降的患者包括这两种技术。 最近开发的神经影像技术对 PVS 和更成熟的结构图像敏感 所提出的研究很重要，因为它将有助于理解 AD。 病理生理机制，从而有助于 AD 的早期诊断和疾病监测。 也很重要，因为它将提供可用于研究其他神经系统疾病的公共资源 以大脑 PVS 受损为特征的疾病结果将产生重要的积极影响。 因为他们将首次识别并绘制人类大脑在衰老过程中的 PVS 变化， 我们共享的 PVS 成像工具也可以更广泛地应用于认知障碍和 AD 个体。 其他团体也进行了广泛的临床和研究应用。