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）是最常见的痴呆症，可以通过脑成像来表征 方法如磁共振成像（MRI）和正电子发射断层扫描（PET）。MRI解释了 结构变化，而PET测量代表根据疾病在大脑中的斑块沉积 进展斑块沉积反映了早期AD的病理生理学，并推测是由于 大脑清洁系统对β-淀粉样蛋白的清除率。最近的研究表明， 脑脊液（CSF）在将废物从脑组织运送到清洁系统中的潜在作用。然而，在这方面， 脑中的CSF流动如何影响废物清除仍然没有很好的理解。因此，建议 多学科研究项目将涉及来自不同和互补的研究人员的合作 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）， 解决CSF流量相关的AD病理生理学。 为了分析颅骨和脑组织之间狭窄空间（蛛网膜下腔[SAS]）中的CSF流动，我们 将采用计算流体动力学（CFD）建模技术，并将CSF流量与神经成像相关联 通过MRI和PET测量的标记物。在这里，首要的假设是，“SAS中的CSF流动受到干扰 导致淀粉样斑块沉积。”为了验证假设，我们将采取以下两个步骤：1） 将招募50名健康的老年人进行MRI扫描。基于解剖和脑脊液速度信息 通过MRI测量，通过CFD模拟分析SAS中的三维流动动力学特性， 2)模拟的CSF性质将通过利用以下因素与局部淀粉样斑块沉积相关： PET成像数据来自NIH资助的母研究（维克森林阿尔茨海默病研究中心）。在这里， 我们将提出一种新的成像标记物用于通过结合成像来去除每个功能性脑区域的淀粉样蛋白， CFD和临床测量。作为替代方法，如果新的成像标记物在治疗中没有用， 由于样本量较小，我们将CFD模型应用于早期AD的较大数据集 成年人了 在该项目完成时，一种新的成像工具，可以量化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病理生理学可能是 使用所提出的方法进行分析。最终，该项目将为人类提供一个生物力学框架。 设计和测试用于治疗AD的介入和外科手术。所开发的软件 程序和成像协议将通过公共软件开发/共享平台共享。