Development of optical Doppler interferometry for the visualization of ocular elasticity and ciliary activity

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.