Beta-Amyloid Clearance Mapping in Alzheimer’s Disease

阿尔茨海默病中的 β-淀粉样蛋白清除图谱

• 批准号: 10196303
• 负责人: Jeongchul Kim
• 金额: $ 42.63万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10196303
• 关键词: 3-Dimensional; Abeta clearance; Address; Adult; Affect; Aging; Algorithmic Software; Alzheimer' s Disease; Alzheimer' s disease therapy; Amyloid; Amyloid beta-Protein; Amyloid deposition; Anatomy; Ancillary Study; Animals; Applications Grants; Atrophic; Biological Process; Biomechanics; Brain; Brain imaging; Brain region; Cerebrospinal Fluid; Cerebrospinal Fluid Pressure; Clinical; Clinical Data; Cognitive; Collaborations; Computer Models; Computer software; Data; Data Set; Dementia; Deposition; Development; Diagnosis; Diagnostic; Disease Progression; Elderly; Equation; Excision; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; Fissural; Functional disorder; Funding; Human; Image; Image Analysis; Imaging Device; Interdisciplinary Study; Intervention; Laws; Liquid substance; Longitudinal cohort; MRI Scans; Machine Learning; Magnetic Resonance Imaging; Measures; Meningeal lymphatic system; Modeling; Monitor; Neurofibrillary Tangles; Operative Surgical Procedures; Parents; Participant; Pattern; Perfusion; Phase; Pontine structure; Positron-Emission Tomography; Process; Production; Property; Protocols documentation; Reporting; Research; Research Personnel; Research Project Grants; Resolution; Resources; Risk; Role; Sample Size; Senile Plaques; Structure; Structure of choroid plexus; Subarachnoid Space; Symptoms; System; Techniques; Testing; Therapeutic; Time; Tissues; United States National Institutes of Health; Velocimetries; abeta accumulation; aging brain; arachnoid villi; base; biomechanical engineering; brain parenchyma; brain tissue; cerebrospinal fluid flow; cisterna magna; clinical center; cohort; cranium; design; forest; glymphatic system; imaging biomarker; imaging modality; improved; informatics tool; insight; large datasets; lateral ventricle; lymphatic vessel; multimodality; nervous system disorder; neuroimaging; neuroimaging marker; novel; population based; pressure; programs; recruit; segmentation algorithm; serial imaging; sharing platform; simulation; software development; tau Proteins; therapy development; tool; wasting

PROJECT SUMMARY Alzheimer’s disease (AD) is the most common form of dementia that can be characterized by brain imaging methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI explains the structural changes, while PET measures represent plaque deposits in the brain according to the disease progression. The plaque deposition reflects early AD pathophysiology and presumably caused by a decrease in the removal rate of beta-amyloid through the cleaning systems of the brain. Recent studies have suggested the potential role of cerebrospinal fluid (CSF) in carrying waste from brain tissue to the cleaning system. However, it is still not well understood how CSF flow in the brain affects waste removal. Therefore, the proposed multidisciplinary research project will involve the collaboration of investigators from diverse and complementary backgrounds (a biomechanical engineer, an MR physicist, a neuroradiologist, and cognitive neuroscientists) to address CSF flow-related AD pathophysiology. To analyze CSF flow in the narrow space between the skull and brain tissue (subarachnoid space [SAS]), we will employ computational fluid dynamic (CFD) modeling technique and correlate CSF flow with neuroimaging markers measured by MRI and PET. Here, the overarching hypothesis is, “Disturbed CSF flow in the SAS leads to the deposition of Amyloid plaque.” To test the hypothesis, we will take the following two steps: 1) Fifty healthy older adults will be recruited for an MRI scan. Based on anatomical and CSF velocity information measured by MRI, three-dimensional flow dynamic properties in SAS will be analyzed through CFD simulation, 2) The simulated CSF properties will be correlated with local amyloid plaque deposition by taking advantage of PET imaging data from the NIH-funded parent study (Wake Forest Alzheimer’s Disease Research Center). Here, we will propose a new imaging marker for amyloid removal for each functional brain region by combining imaging, CFD, and clinical measures. As an alternative approach, in case the new imaging markers are not useful in healthy older adults due to the small sample size, we will apply the CFD model to larger datasets for early AD adults. At the completion of this project, a new imaging tool to quantify CSF flow in the SAS and evaluate its effects on amyloid deposition and removal will be proposed. AD pathophysiology at an early stage in older adults can be analyzed using the proposed approach. Ultimately, this project will provide a biomechanical framework for the design and test of interventional and surgical procedures for the treatment of AD. The developed software programs and imaging protocols will be shared through a public software development/sharing platform.

项目摘要 阿尔茨海默氏病（AD）是最常见的痴呆形式，可以通过脑成像为特征 磁共振成像（MRI）和正电子发射断层扫描（PET）等方法。 MRI解释说 结构性变化，而宠物措施则表示根据疾病中的斑块沉积物 进展。斑块沉积反映了早期AD病理生理学，可能是由于下降而引起的 通过大脑清洁系统的β-淀粉样蛋白的去除率。最近的研究表明 脑脊液（CSF）在从脑组织到清洁系统中的废物中的潜在作用。然而， 仍然不太了解大脑中的CSF流动如何影响废物的清除。因此，提议 多学科研究项目将涉及潜水员和完善的调查人员的合作 背景（生物力学工程师，MR物理学家，神经放射学家和认知神经科学家） 介绍与CSF流动有关的AD病理生理学。 为了分析颅骨和脑组织之间狭窄空间中的CSF流动（蛛网膜下腔空间[SAS]），我们 将采用计算流体动力学（CFD）建模技术，并将CSF与神经成像相关联 MRI和PET测量的标记。在这里，总体假设是：“ SAS中的CSF流动受干扰 导致淀粉样菌斑的沉积。“为了检验假设，我们将采取以下两个步骤：1） 将招募五十名健康的老年人进行MRI扫描。基于解剖学和CSF速度信息 通过MRI测量，将通过CFD模拟分析SAS中的三维流动动态特性， 2）模拟的CSF特性将通过利用优势与局部淀粉样斑块沉积相关 NIH资助的父母研究（Wake Forest Alzheimer's Disean Research Center）的PET成像数据。这里， 我们将通过组合成像，为每个功能大脑区域的淀粉样蛋白去除淀粉样蛋白的新成像标记， CFD和临床措施。作为另一种方法，如果新成像标记在 由于样本量较小，健康的老年人健康，我们将将CFD模型应用于较大的数据集以进行早期广告 成年人。 该项目完成后，一种新的成像工具，用于量化SAS中的CSF流量并评估其对 将提出淀粉样蛋白沉积和去除。老年人早期的AD病理生理学可以是 使用建议的方法分析。最终，该项目将为该项目提供生物力学框架 介入和外科手术治疗AD的设计和测试。开发的软件 程序和成像协议将通过公共软件开发/共享平台共享。