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

基本信息

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
项目类别：
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&apos 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

项目摘要

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的乙型功能来预测乙型功能对比度传递项目摘要：最近确定的糖基系统，该系统调节大脑的交换间质性液体和脑脊液液已被证明在清除废品中起主要作用来自大脑。患有痴呆或老年的人的糖基糖间隙减少，这就是假设有助于蛋白质聚集，神经毒性和认知能力下降。变化的影响尚未全面研究在糖酶功能中，作为评估的临床方法缺乏胶囊系统。用于评估胶囊功能的敏感且无创的成像工具是显然需要。该建议通过测试量化敏感的非侵入性方法来满足这一需求大脑浪费清除率很容易翻译成诊所。鼻子到大脑（N2B）传递是一个有用的工具直接传递到大脑，并假设利用糖性视频在整个大脑中分发组织。我们将测试非侵入性宠物/MRI可视化的大脑的N2B宠物示踪剂清除率是否清除提供有关糖函数的有意义的信息，并与已知的解剖变化相关荧光显微镜。我们的宠物方法将与Glycphatic的MRI当前黄金标准进行比较成像并在糖基改变的物理和病理模型中进行了测试。如果成功的话，这项研究可以在神经毒性病理发作之前，提供了一种工具，用于早期检测降低的糖性功能。