Imaging structural and mechanical properties in cardiovascular tissue using optical polarization tractography

[EMBARGOED UNTIL 6/1/2023] Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the US. Every 36 seconds, one person dies from CVD [1]. Structural deficiencies and secondary changes induced by either abnormal functioning of related mechanisms or irregular physiological loading are deciding factors in the development of CVD. CVD's high mortality rate has increasingly motivated efforts to better understand the underlying mechanisms associated with normal structure and their CVD-provoked modifications. Thorough knowledge about disease-driven events at the tissue and cellular level eventually leads to early diagnosis prior to the appearance of clinical symptoms at the organ-level and the cardiovascular system-level. Common clinical imaging technologies such as MRI, PET, and CT are well-known to cover organ, and system-level events; however, they suffer from low resolution, making it difficult to resolve delicate layers in cardiovascular tissues. On the other hand, microscopic techniques provide high resolution, however, they are limited by their small field of view and their insufficient effective imaging depth. To address these issues, this dissertation focuses on characterization of the fiber architecture of Extra Cellular Matrix (ECM) in cardiovascular tissues, including carotid artery and Mitral Valve (MV) tissues, by utilizing a newly-developed nondestructive, micrometer-scale depth-resolved imaging technique based on locally-polarized sensitive optical coherence tomography (PSOCT) measurements. The system can measure intrinsic optical properties of fibrous tissues, such as birefringence and fiber orientation, and visualize them in three-dimensional (3D) space. The orientation data is used to trace elastin and collagen fibers using a tractography method in different layers of ECM. An automatic multi-feature image segmentation approach was developed to extract MV layers and quantify the layer-specific characteristics of MVs such as thickness, fiber orientation, and alignment. These parameters play crucial roles in normal biomechanical functioning in MV, and their alterations are associated with disease progression. Furthermore, the interrelationship between the structural parameters and mechanical responses of MV tissue was studied by designing and 3D printing a mechanical setup to integrate PSOCT imaging with biaxial loading of the tissue. Additional information was obtained by visualizing layer-specific deformation of fiber architecture in anterior leaflet of mitral valve tissue in response to equilibrium biaxial loading. To measure 3D displacement maps and 3D strain tensors across the stretched tissue, a 3D optical coherence elastography (OCE) technique based on intensity volumes was developed. Simultaneous structure and elastography imaging were applied to reveal detailed location-specific and layer-specific mechanical anisotropy in anterior leaflet of MV tissues. Special effort was made in this dissertation to reveal detailed fiber structures and their interrelation with mechanical functionality in cardiovascular tissues; these relationships can remarkably improve mechanical modeling and tissue engineering in this field. These studies will facilitate understanding advanced diseased-related structural remodeling in response to simulated physiological or mechanical disease environments. In addition, due to the fast progress of fiber optic technology in PSOCT imaging, local polarization sensitive measurements can be extended to in vivo studies in the future.Includes bibliographical references