Predicting glymphatic function via PET/MR imaging biomarkers and Nose to Brain contrast delivery

通过 PET/MR 成像生物标志物和鼻到脑对比剂输送来预测类淋巴功能

• 批准号: 10370078
• 负责人: Kurt R Zinn
• 金额: $ 41.79万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370078
• 关键词: 3-Dimensional; Address; Aging; Alzheimer' s Disease; Amyloid beta-Protein; Anatomy; Autopsy; Biological Markers; Blood Circulation; Brain; Cells; Cephalic; Cerebrospinal Fluid; Cervical lymph node group; Clinic; Clinical; Contrast Media; Data; Data Set; Dementia; Detection; Development; Diagnosis; Diagnostic; Disease; Disease model; Early Diagnosis; Evaluation; FDA approved; Fluorescence Microscopy; Functional disorder; Future; Gadolinium; Goals; Gold; Hepatic; Histologic; Human; Image; Imaging Device; Immune; Immunohistochemistry; Impaired cognition; Incidence; Individual; Injections; Intercellular Fluid; Intervention; Investigation; Label; Ligation; Lymphatic; Lymphatic System; Lymphatic clearance; Lymphatic function; Magnetic Resonance Imaging; Measures; Mediating; Meningeal lymphatic system; Meninges; Methods; Modality; Modeling; Nerve Degeneration; Neuraxis; Neurodegenerative Disorders; Nose; Outcome; Pathologic; Pathology; Patient Care; Patients; Play; Positron-Emission Tomography; Preventive care; Proteins; Radioactive; Rattus; Reporting; Research; Rodent; Role; Route; System; Techniques; Testing; Tracer; Translations; United States; Waste Products; aged; base; brain pathway; brain tissue; clinical imaging; cost; cribriform plate; fluorophore; functional disability; glymphatic clearance; glymphatic function; glymphatic system; human old age (65+); imaging agent; imaging biomarker; imaging modality; in vivo imaging; insight; lymph flow; lymphatic vessel; molecular imaging; nervous system disorder; neuropathology; neurotoxic; neurotoxicity; non-invasive imaging; pathological aging; perineural; perivascular channels; physical model; pre-clinical; protein aggregation; quantitative imaging; radiotracer; tool; wasting

PROJECT TITLE: Predicting glymphatic function via PET/MR imaging biomarkers and Nose to Brain contrast delivery PROJECT ABSTRACT: The recently identified glymphatic system, which modulates exchange of the brain’s interstitial fluid and cerebrospinal fluid, has been shown to play a major role in the clearance of waste products from the brain. Individuals with dementia or old age show diminished glymphatic clearance, which is hypothesized to contribute to protein aggregation, neurotoxicity, and cognitive decline. The impact of changes in glymphatic function have not been comprehensively investigated, as clinical methods to evaluate the glymphatic system are lacking. A sensitive and noninvasive imaging tool for evaluation of glymphatic function is clearly needed. This proposal addresses this need by testing sensitive, non-invasive methods for quantifying brain waste clearance that are readily translatable to the clinic. Nose to brain (N2B) delivery is a useful tool for direct delivery to the brain and is hypothesized to utilize glymphatic vessels for distribution throughout the brain tissue. We will test whether N2B PET tracer clearance from the brain visualized by noninvasive PET/MRI provides meaningful information about glymphatic function, and correlate with known anatomical changes by fluorescence microscopy. Our PET approach will be compared to the MRI current gold standard for glymphatic imaging and tested in physical and pathological models of glymphatic alterations. If successful, this study could provide a tool for early detection of diminished glymphatic function before the onset of neurotoxic pathology.

项目名称：通过 PET/MR 成像生物标志物和鼻子到大脑预测类淋巴功能 造影剂输送 项目摘要：最近发现的类淋巴系统可以调节大脑的 间质液和脑脊液已被证明在废物的清除中发挥着重要作用 来自大脑。患有痴呆症或年老的人表现出类淋巴清除能力下降，这是 推测会导致蛋白质聚集、神经毒性和认知能力下降。变化的影响 类淋巴功能的相关性尚未得到全面研究，作为临床评估方法 类淋巴系统缺乏。用于评估类淋巴功能的灵敏且无创的成像工具是 显然需要。该提案通过测试敏感的、非侵入性的量化方法来满足这一需求 脑废物清除很容易转化为临床。鼻到脑（N2B）传输是一个有用的工具 直接输送到大脑，并假设利用类淋巴管分布到整个大脑 组织。我们将测试是否通过无创 PET/MRI 可视化 N2B PET 示踪剂从大脑中的清除 提供有关类淋巴功能的有意义的信息，并通过以下方式与已知的解剖学变化相关联 荧光显微镜。我们的 PET 方法将与 MRI 当前类淋巴系统黄金标准进行比较 成像并在类淋巴管改变的物理和病理模型中进行测试。如果成功的话，这项研究可以 提供了一种在神经毒性病理发生之前早期检测类淋巴功能减弱的工具。