UC Irvine

Understanding the mechanical properties of soft biological tissues is fundamental to interpreting their physiological function and pathological remodeling. In the eye and brain—two of the most mechanically sensitive organs in the human body—local stiffness governs essential processes including optical focusing, intraocular pressure (IOP) homeostasis, axonal transport, extracellular matrix (ECM) regulation, and neurovascular coupling. Yet, despite the centrality of biomechanics, quantitative measurement of soft-tissue elasticity at micrometer scale remains an unresolved challenge. Conventional elastography techniques such as magnetic resonance or ultrasound elastography lack the spatial resolution required to resolve thin ocular structures, while mechanical testing is restricted to excised samples and cannot characterize in situ behavior. Optical coherence elastography (OCE), an extension of optical coherence tomography (OCT), has emerged as a promising solution by enabling nanometer-scale displacement detection and quantitative elasticity mapping in living tissues. However, full realization of OCE’s potential requires advances in system engineering, signal processing, excitation control, and biomechanical modeling.This dissertation develops a unified OCE framework that integrates phase-sensitive detection, multimodal excitation strategies, and quantitative inversion algorithms to enable high-precision mechanical imaging across ocular and neural systems. At the systems level, three complementary OCE platforms were established. First, a high-speed phase-resolved spectral-domain OCT system was engineered with a broadband 890-nm light source, optimized interferometer design, and nanometer-level phase stability. This system was coupled with a mechanical shaker that generated broadband elastic waves capable of propagating through the entire globe, enabling quantitative in vivo assessment of optic nerve head (ONH) stiffness under controlled IOP modulation. Second, a confocal acoustic-radiation-force OCE system was constructed to image equatorial scleral anisotropy. The system used a ring-shaped 6.8-MHz ultrasound transducer integrated with the OCT detection path, allowing spatially localized generation of guided waves and direction-dependent elasticity mapping. Third, a wide-field compressional OCE platform was developed for ex vivo mouse-brain imaging. This system incorporated a calibrated silicone reference layer for stress estimation, synchronized preload/actuation control, and optional optical clearing for improved depth penetration.The first biological application focused on the ONH, a biomechanically vulnerable site central to glaucoma. Using the shaker-based platform, both ex vivo and in vivo experiments demonstrated that shear-wave velocity and reconstructed Young’s modulus increased monotonically with IOP, confirming nonlinear stiffening under load. This work provided the first demonstration of in vivo ONH OCE in rabbits and established direct measurement of ONH biomechanics under physiological pressure regulation.The second application investigated multiscale anisotropy in the equatorial sclera, a region essential to ocular shape regulation and load transmission. Direction-dependent wave propagation was quantified across nasal, temporal, superior, and inferior quadrants at multiple IOP levels. Both OCE and complementary ultrasonic elastography revealed consistently higher wave speeds in the circumferential (equatorial) direction than in the meridional direction. Structural correlation using polarized light microscopy, scanning electron microscopy, and transmission electron microscopy revealed that mechanical anisotropy diverged from planar fiber orientation alone and instead reflected a multiscale organization of interwoven collagen lamellae.The third application extended OCE to neural tissue, introducing a wide-field compressional system capable of mapping elasticity across entire mouse-brain slices. Strain and elasticity maps revealed clear contrast between gray and white matter, laminar structure in the hippocampus and cerebellum, and strong correspondence with histological microarchitecture. Optical clearing improved depth visibility without altering intrinsic stiffness distribution, demonstrating compatibility between OCE and tissue-transparency methods. Collectively, this dissertation advances OCE as a quantitative, multi-regime elastography platform capable of probing biomechanics across ocular and neural tissues. The engineering innovations and biological findings presented here establish the foundation for future in vivo clinical translation, MHz-rate OCE, and integration of elastography with machine-learning–enabled analysis for real-time mechanical assessment.