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: 10480056
• 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/10480056
• 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; 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; 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; diagnostic tool; glymphatic system; healthy aging; human data; hyperphosphorylated tau; imaging facilities; improved; in vivo; innovation; insight; interest; nervous system disorder; neuroimaging; neurovascular; normal aging; secondary analysis; tau Proteins; 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.

项目摘要 血管周空间（PVS）是Artiolos，静脉和毛细血管周围的区域 通过在星形胶质细胞端面表达的Aquaporin-4通道清除代谢废物，参与 血脑屏障运输。 PV最近通过大脑间隙中的潜在作用而引人注目 流体排水和废物清除，以及阿尔茨海默氏病（AD）和其他的发病机理 神经退行性疾病。尽管动物研究精确阐明了这种机制，但人类的数据 相对粗糙，仅限于临床磁共振图像上可见PV的视觉计数，这 限制了我们对人类衰老中PV的形态，生物物理特性和分布的理解 广告。长期目标是了解PV在大脑健康中的作用以及其在AD中的变化程度。 该项目的目的是绘制PVS流体的形态和扩散特征 健康的衰老，以及在AD的早期阶段如何改变它。中心假设是成像衍生 PVS流体特性（例如占据体积和差异特性）是差异性和选择性的 与正常衰老相比，认知能力下降和AD的改变。该提议的基本原理是 PVS的体内无创映射提供了有关AD病理生理学的机械洞察力。这 拟议的工作还将开发广泛适用的开放资源来映射PVS形态和扩散 可以应用于多种神经系统疾病的特性。中心假设将通过 追求三个具体目标：1）表征普通老龄化个体中PVS流体的变化，没有认知 拒绝AD病理学的证据，并评估图像获取策略对结果的影响 措施； 2）确定认知能力下降和AD病理患者的PV改变； 3）确定 PVS与心血管危险因素与AD病理学相关的程度。我们将追求这些 通过将基于创新MRI的计算技术应用于正常衰老的最近可用数据和 多项大型NIH资助研究的认知能力下降的患者。计算技术包括 最近开发的神经影像技术对PV敏感和更既定的结构图像 分析技术。拟议的研究很重要，因为它将有助于理解AD 病理生理机制，因此有助于对AD的早期诊断和疾病监测。 之所以重要，是因为它将使公共资源可用于研究其他神经系统 大脑中PV受损的疾病。结果将产生重要的积极影响 立即，因为他们将首次识别和映射PVS在衰老中的人脑中的PV改变， 认知受损和广告个体。我们共享的PVS成像工具也可以更广泛地应用于 其他群体也广泛的临床和研究应用。