Development of Photothermal Optical Coherence Tomography for Retinal Imaging

Abstract

There is a need for molecular imaging techniques in the eye to better understand disease progression, identify early disease markers, and evaluate new treatment options. Optical coherence tomography (OCT) provides high resolution, volumetric images of tissue structure and has become a standard eye imaging technique both at the pre-clinical and clinical levels. However, the OCT signal is based on tissue scattering and does not provide molecular contrast. In this dissertation, photothermal OCT (PT-OCT) is developed for retinal imaging to provide molecular contrast to OCT. Changes in pigmentation are observed in ocular diseases such as age-related macular degeneration (AMD) and could be predictive of disease progression. Nanoparticles have also been investigated as potential drug carriers to treat AMD. Additionally, dyes such as indocyanine green are used to stain certain layers of the retina and increase contrast during ocular surgeries. In this dissertation, PT-OCT is demonstrated in the eye for the first time. Melanin and gold nanorods were imaged with PT-OCT in vivo in mouse and zebrafish eye models. Additionally, indocyanine green was imaged with PT-OCT in a mock surgical procedure in ex vivo pig eyes using sub-clinical dye concentrations. An algorithm was also created to correct imaging artifacts and effectively improve the axial resolution of PT-OCT. This dissertation thus outlines pre-clinical and clinical applications of PT-OCT for retinal imaging.