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

项目总结 快速发展的“弹性地形学”领域在回答基础科学方面取得了一些重大成功。 提出问题并改进临床诊断和治疗。例如，肝脏僵硬的增加强烈地 与纤维化等晚期肝病相关，主动脉僵硬增加与 心血管疾病和多发性癌症可以用粘弹性异质性来评估。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，例如 作为肌肉收缩和角膜屈光。然而，局部和全局生物力学的变化 与衰老和神经退行性疾病相关的脑组织特性还没有得到广泛的研究 进行了研究和量化。这些变化可以作为潜在的生物标记物，用于预测肿瘤的发生和发展。 疾病。病理学和尸检案例研究提供了一些定性的见解，以及磁共振 弹性成像(MRE)研究显示了一些一般模式。然而，目前的技术需要 技术的完善和大脑进化之间的关系还有很多有待阐明 生物力学和这些复杂的过程。有几种使用光学相干的方法 层析成像(OCT)是一种高分辨率成像手段，用于获得生物组织的力学特性。 这些技术通常被称为光学相干弹性成像(OCE)，并且已经证明 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被应用于先进的小鼠 神经病理模型。将在小鼠体内/体外进行OCE，以研究衰老过程 和阿尔茨海默氏症。剪切波通过换能器和OCT成像引入脑组织 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 大脑皮质组织相对于时间的僵硬程度将被量化。具体地说，混响的使用 用于弹性成像的剪切波场，它利用来自边界和组织的不可避免的反射 不均匀性，允许估计剪切波速，这与弹性模数直接相关。 软组织。该项目需要精确的工程设计，这提出了一个可寻址的实验 挑战。这个项目的目标是量化剪切波的速度(与组织的硬度有关) 在小鼠模型中，随着年龄或阿尔茨海默病的发生和发展而变化，直接 对未来人类研究的影响。

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.