Patient specific computational modeling of fluid-structure interactions of cerebrospinal fluid for biomarkers in Alzheimer's disease

阿尔茨海默病生物标志物脑脊液流固相互作用的患者特定计算模型

• 批准号: 10644281
• 负责人: Patrick Fillingham
• 金额: $ 30.36万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2025-09-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644281
• 关键词: 4D MRI; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease patient; Anatomy; Area; Benchmarking; Biological Markers; Blood; Blood flow; Brain; Brain Mapping; Carotid Arteries; Cerebral aqueduct; Cerebrospinal Fluid; Cerebrum; Computer Models; Coupled; Data; Development; Disease; Early Diagnosis; Ensure; Evolution; Excision; Frustration; Geometry; Image; Impairment; Individual; Intracranial Pressure; Link; Liquid substance; Literature; MRI Scans; Magnetic Resonance; Magnetic Resonance Angiography; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methodology; Methods; Modeling; Modulus; Morbidity - disease rate; Multicenter Studies; Neurofibrillary Tangles; Pathway interactions; Patients; Phase; Phlebography; Physiological; Play; Population; Procedures; Property; Proteins; Protocols documentation; Public Health; Research; Resolution; Role; Scanning; Stress; Structural Models; Structure; Structure of jugular vein; Subarachnoid Space; Techniques; Test Result; Third ventricle structure; Time; Tissues; Validation; Venous; Work; amyloid peptide; basilar artery; brain tissue; cerebrospinal fluid flow; cohort; cranium; disease diagnosis; foramen magnum; healthy volunteer; in vivo; mechanical properties; mortality; novel; potential biomarker; residence; simulation; spatiotemporal; tau-1; tool; trend; vibration

Alzheimer's Disease has become a daunting public health concern with devastating effects on the individual and societal level. Early detection and diagnosis of the disease would be incredibly beneficial in the effort to reduce morbidity and mortality of the disease, yet reliable methods of early detection remain frustratingly elusive. Recent work has shown impairment of cerebrospinal fluid (CSF) flow in and around the brain, and how that impairment is linked to brain tissue stiffness, play a vital role in the early development of Alzheimer's Disease pathology. Unfortunately, existing candidates for measuring CSF flow and brain tissue stiffness are either highly invasive or semiquantitative analyses that cannot quantify key mechanical properties of brain tissue deformation and how it relates to the convective transport of AD-related proteins (such as amyloid -peptide and phosphorylated tau) via CSF flow. To overcome these obstacles, we will develop a computational model capable of accurately calculating CSF velocities and the stress-strain status of the brain cortex. Our approach will use state of the art, non-invasive MRI scans in concert with patient-specific computational fluid dynamic (CFD) modeling of CSF and blood flow to determine the physiological conditions of flow in the skull and their interactions with brain tissue. To account for the deformation of brain tissue and the resulting effects on fluid transport, the fluid simulations will be coupled with a structural model of the brain tissue via fluid-structure interaction (FSI) modeling. The results from this technique will allow for the development of novel, noninvasive and quantitative biomarkers such as brain "stiffness" (a surrogate for the hallmark histopathological plaques and tangles), CSF residence time in the subarachnoid space (related to protein-removal rates), and other hydrodynamic factors such as intracranial pressure pulsatility.

阿尔茨海默氏病已成为令人畏惧的公共卫生问题，对人类造成毁灭性影响 个人和社会层面。疾病的早​​期发现和诊断将非常有益 努力降低该疾病的发病率和死亡率，但仍然存在可靠的早期检测方法 令人沮丧的是难以捉摸。最近的研究表明，脑脊液（CSF）及其周围的流动受到损害。 大脑，以及这种损伤如何与脑组织僵硬相关，在早期发展中发挥着至关重要的作用 阿尔茨海默病病理学。不幸的是，现有的用于测量脑脊液流量和脑组织的候选药物 刚度要么是高度侵入性的，要么是半定量分析，无法量化关键的机械性能 脑组织变形及其与 AD 相关蛋白质（例如 淀粉样蛋白肽和磷酸化 tau 蛋白）通过脑脊液流。为了克服这些障碍，我们将开发一个 能够准确计算 CSF 速度和应力应变状态的计算模型 大脑皮层。我们的方法将使用最先进的非侵入性 MRI 扫描，并结合患者的具体情况 CSF 和血流的计算流体动力学 (CFD) 建模以确定生理条件 颅骨中的血流及其与脑组织的相互作用。考虑脑组织的变形和 由此产生的对液体运输的影响，液体模拟将与大脑的结构模型相结合 通过流固耦合（FSI）建模组织。该技术的结果将允许 开发新型、非侵入性和定量的生物标志物，例如大脑“僵硬”（大脑“僵硬”的替代品） 标志性组织病理学斑块和缠结），脑脊液在蛛网膜下腔的停留时间（与 蛋白质去除率），以及其他流体动力学因素，例如颅内压脉动。