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

点击翻译按钮获取中文摘要

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.