Functional optical imaging techniques have become increasingly important due to their high resolution and non-invasive nature, and have been used to address many unmet needs in the biomedical imaging field. In the area of ophthalmology, mechanical properties have been shown to be an early indicator of retinal disease, but current imaging modalities are unable to provide high resolution in-vivo imaging to capture the minute changes in the elasticity of thin tissue layers at the back of the eye. For respiratory diseases, the ciliary cell function inside the airway have been discovered to play an important role in respiratory health and the onset of disease. Similarly, current techniques are not equipped to image and characterize the cellular level changes in in-vivo tissues. Phase-resolved Doppler (PRD) imaging is a technology developed by our F-OCT lab, primarily for visualizing blood flow and angiography. Recently, it has been determined that the PRD technique is able to provide high phase sensitivity, which can be used to obtain the tissue displacement as well as particle motions. Using this principle, we developed two types of imaging systems: confocal acoustic radiation force optical coherence elastography (ARF-OCE) and spectrally-encoded interferometric microscopy (SEIM). Using the confocal ARF-OCE system, we present the first spatially mapped elasticity imaging in a live animal retina, and obtained a better understanding of the elasticity of different retinal layers. With the SEIM system, we introduced a novel method of spatially tracking ciliary activity in real-time of in vitro tracheal and oviduct tissues. We demonstrate that the SEIM system can image and quantify ciliary beating frequency and ciliary beating pattern with high speed and large field of view. While both these technologies use the PRD technique, the optical system has been optimized for the respective applications. The results in this dissertation serve as a stepping stone to the optimization and ultimately, the clinical translation of the PRD technique to diagnostic imaging. The developed technology has great potential for clinical diagnosis and management of a number of ocular disease, such as age related macular degeneration, glaucoma, presbyopia and myopia, as well as airway diseases such as asthma.

Mechanical elasticity often serves as a major indicator for pathological changes in ocular as well as intravascular diseases. For example, age-related macular degeneration is an ocular disease that occurs in the posterior eye, where central vision gets damaged due to drusen formation and neovascularization. The mechanical elasticity of the tissue is often altered during the onset of disease before structural changes are detectable with existing technologies. It is necessary to detect these changes early and provide timely treatment due to either the irreversible nature of the disease progression or the fatal consequences associated with late diagnosis. This thesis focuses on the development of an acoustic radiation force optical coherence elastography (ARF-OCE) system to map the mechanical elasticity of tissues, and the translation of this laboratory technology to in vivo animal studies. This technique uses ultrasonic excitation to apply a force onto the tissue and optical coherence elastography to detect the spatial and frequency responses of the tissue, which combines to quantify the elasticity and provide an elasticity map. The resonance frequency method is validated and used to measure the bulk modulus of the tissue while a Voigt spring model calculates the individual layer elasticity. We first test the feasibility of the system using tissue-mimicking phantoms. Then we perform tissue imaging on the ex vivo anterior and posterior eye, where we are able to provide quantified elasticity maps of the rabbit cornea and porcine retina The system is then translated to in vivo imaging, for which quantified elasticity mapping of the rabbit retinal layers can be obtained. In addition, we have also fabricated an ARF-OCE catheter with a diameter of 3.5 mm, which was validated using phantom studies, and intravascular imaging was performed on a human cadaver artery. This study is a major stepping stone to the translation of the ARF-OCE technology in measuring the mechanical properties of tissues in clinical settings. Future studies using this technology include monitoring the retinal elasticity during and after electrode stimulation treatment and also intravascular elasticity imaging to diagnose atherosclerosis.

In this study, the efforts conducted in suppressing the effects of NURD on acquired OCT images are described. The work is divided into theoretical and experimental sections. A part of the theoretical work is focused on reconstruction of a dynamic programming method that was previously used for NURD correction and implementing it in correcting the current data. Finite element analysis of the press fitting method with ABAQUS software is another portion of the theoretical work in this study. The image post-processing algorithm was validated based on a statistical method and using sets of data from an in vivo model. It made a significant difference between images before and after correction.

Experimental work mainly focused on improving the quality of probes by making them shorter and more axially symmetric. Four different potential methods were considered during the experiments with the main focus on their feasibility and reliability. The newly developed press fitting method in manufacturing of the probes was considered to be the most promising approach because it is clean, fast, strong and repeatable.