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

点击翻译按钮获取中文摘要

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.