Investigation of Brain Elasticity in Aging and Alzheimer's Disease Enabled by Optical Coherence Elastography

通过光学相干弹性成像技术研究衰老和阿尔茨海默病中的脑弹性

• 批准号: 10324551
• 负责人: Gary Ruian Ge
• 金额: $ 5.1万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2024-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10324551
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Autopsy; Basic Science; Biological; Biomechanics; Brain; Brain region; Breast; Cardiovascular Diseases; Case Study; Categories; Complex; Computing Methodologies; Cornea; Data; Disease; Disease Progression; Disease model; Elasticity; Elderly; Engineering; Evolution; Fibrosis; Future; Goals; Health Promotion; Heart; Heterogeneity; Human; Image; Imaging Techniques; In Situ; Injury; Investigation; Lateral; Light; Link; Liver; Liver diseases; Longevity; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Measurement; Measures; Mechanics; Methods; Modeling; Modification; Modulus; Mus; Muscle; Muscle Contraction; Nerve Degeneration; Neurodegenerative Disorders; Onset of illness; Optical Coherence Tomography; Optics; Pathology; Pattern; Physicians; Planet Earth; Population; Process; Property; Protocols documentation; Research; Research Personnel; Research Project Grants; Resolution; Scientist; Skin; Speed; Structure; Surveys; Techniques; Testing; Time; Tissues; Training; Transducers; Ultrasonography; Variant; base; brain tissue; clinical diagnostics; elastography; engineering design; ex vivo imaging; high resolution imaging; imaging modality; imaging system; improved; in vivo; in vivo imaging; insight; mechanical properties; millimeter; mouse model; neuroimaging; neuropathology; normal aging; physical property; potential biomarker; pre-clinical; soft tissue; success; theories; viscoelasticity

PROJECT SUMMARY The rapidly advancing field of “elastography” has had some major successes in answering basic science questions and improving clinical diagnostics and therapies. For example, increased liver stiffness is strongly correlated with advanced liver disease such as fibrosis, increased aortic stiffness has been linked with cardiovascular disease, and multiple cancers can be assessed with viscoelastic heterogeneity. Other studies have used the physical properties of tissue to investigate the relationship between structure and function, such as muscle contraction and corneal refraction of light. However, changes in the local and global biomechanical properties of brain tissue associated with aging and neurodegenerative diseases have not been extensively studied and quantified. These changes could serve as potential biomarkers for the onset and progression of disease. Pathology and autopsy case studies have provided some qualitative insight, and magnetic resonance elastography (MRE) studies have demonstrated some general patterns. However, current techniques require technical refinement and much remains to be elucidated about the relationship between the evolution of brain biomechanics and these complex processes. There are several approaches that employ optical coherence tomography (OCT), a high-resolution imaging modality, to obtain the mechanical properties of biological tissues. These techniques are generally referred to as optical coherence elastography (OCE), and have demonstrated promising applications with studies in cornea, breast, muscle, heart, and skin. In this project, recent advances in OCT and elastography techniques are applied to advanced murine neuropathology models. OCE will be performed in mice ex vivo / in situ and in vivo to study the aging process and Alzheimer’s disease. Shear waves are introduced into brain tissue via transducers, and an OCT imaging system captures volumetric data with lateral and axial resolutions of a few microns. Variations in the softness and stiffness of cortical brain tissue with respect to time will be quantified. Specifically, the use of reverberant shear wave fields for elastography, which takes advantage of inevitable reflections from boundaries and tissue inhomogeneities, allows for estimation of the shear wave speed, which is directly related to the elastic modulus of soft tissues. The project requires precise engineering design, which presents an addressable experimental challenge. The goal of this project is to quantify how shear wave speeds (related to stiffness of tissues) change with aging or the onset and progression of Alzheimer’s disease using mouse models, with direct implications to future human studies.

项目摘要 快速发展的“弹性成像”领域在回答基础科学方面取得了一些重大成功 问题和改进临床诊断和治疗。例如，增加的肝硬度强烈地 与晚期肝病如纤维化相关，主动脉僵硬度增加与 心血管疾病和多种癌症可以用粘弹性异质性进行评估。其他研究 利用组织的物理特性来研究结构和功能之间的关系， 如肌肉收缩和角膜对光的折射。然而，局部和整体生物力学的变化 与衰老和神经退行性疾病相关的脑组织的性质还没有被广泛地 研究和量化。这些变化可以作为潜在的生物标志物的发病和进展， 疾病病理学和尸检案例研究提供了一些定性的见解， 弹性成像（MRE）研究已经证明了一些一般模式。然而，目前的技术需要 技术上的改进和许多有待阐明的关系， 生物力学和这些复杂的过程。有几种方法采用光学相干 断层扫描（OCT），一种高分辨率成像方式，用于获得生物组织的机械特性。 这些技术通常被称为光学相干弹性成像（OCE），并且已经证明了 在角膜、乳房、肌肉、心脏和皮肤的研究中有很好的应用前景。 在这个项目中，OCT和弹性成像技术的最新进展应用于先进的小鼠 神经病理学模型OCE将在小鼠体内/原位和体内进行，以研究老化过程 和老年痴呆症剪切波通过换能器被引入脑组织，并且OCT成像 系统以几微米的横向和轴向分辨率捕获体积数据。柔软度的变化 和皮质脑组织相对于时间的硬度进行量化。特别是混响的使用 弹性成像的剪切波场，利用边界和组织不可避免的反射 不均匀性，允许估计剪切波速度，这是直接相关的弹性模量 软组织。该项目需要精确的工程设计，这提供了一个可寻址的实验 挑战.该项目的目标是量化剪切波速度（与组织刚度相关） 随着年龄的增长或阿尔茨海默病的发病和进展的变化，使用小鼠模型，直接 对未来人类研究的影响。