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到脑预测淋巴功能