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.

项目标题：通过PET/MR成像生物标志物和鼻子对脑预测淋巴功能 对比度传递 项目摘要：最近发现的淋巴系统，它调节大脑的 间质液和脑脊液，已被证明在清除废物方面发挥主要作用。 来自大脑。痴呆症或老年患者表现出淋巴清除量减少，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 在淋巴功能方面还没有得到全面的研究，作为临床评价的方法 缺乏淋巴系统。一种灵敏且无创的评估淋巴功能的成像工具是 显然是有必要的。这项建议通过测试敏感的、非侵入性的量化方法来满足这一需求 大脑废物清除，很容易翻译到临床。鼻到脑(N2B)交付是一种有用的工具 直接输送到大脑，假设是利用淋巴管在整个大脑中分布 组织。我们将测试非侵入性PET/MRI是否显示N2B PET示踪剂从大脑中清除 提供有关淋巴功能的有意义的信息，并与已知的解剖变化相关联 荧光显微镜。我们的PET方法将与目前MRI诊断淋巴疾病的金标准进行比较 在淋巴改变的物理和病理模型中进行成像和测试。如果成功，这项研究可能会 为在神经毒性病理发生之前及早发现淋巴功能减退提供了一种工具。