Contrast-Enhanced Optical Coherence Tomography Using Gold Nanorods

Abstract

MOLECULAR PHYSIOLOGY AND BIOPHYSICS

Contrast-Enhanced Optical Coherence Tomography Using Gold Nanorods

Andrew Gordon

Dissertation under the direction of Professor John S. Penn

Optical coherence tomography (OCT) is the clinical standard for retinal imaging because it provides fast, high-resolution images of tissue structure. The purpose of our research is to improve OCT systems so that they can convey data about physiological changes in tissue. To accomplish this we demonstrate contrast-enhancement of OCT imaging using gold nanorods (GNR). GNR are excellent candidates for OCT contrast agents because of their unique optical properties, and we demonstrate their utility in the setting of standard OCT imaging, as well as imaging with OCT adjuncts. These adjuncts include photothermal OCT (PT-OCT) and spectral-fractionation OCT (SF-OCT). We explore how the surface functionalization of GNR affects its utility as an OCT contrast agent. We then image untargeted and ICAM2-targeted GNR in vivo with OCT and PT-OCT imaging. PT-OCT imaging was performed in wild-type C57BL/6 and albino BALB/c mice. Much of the in vivo imaging is performed in the laser-induced choroidal neovascularization (LCNV) model, with or without the additional intravitreal delivery of a neutralizing monoclonal anti-vascular endothelial growth factor (anti-VEGF) antibody. Additionally, we perform in vitro testing of GNR with SF-OCT in tissue phantoms. Our results demonstrate that surface coatings of GNR are major determinants of their behavior in vivo. We find that GNR can provide contrast on standard OCT imaging in the vitreous, but not the retina. We find that PT-OCT imaging of targeted or untargeted GNR demonstrates contrast enhancement of LCNV lesions on retinal imaging, though we do not conclusively demonstrate a targeting effect. We demonstrate that PT-OCT imaging reports reduced GNR accumulation in LCNV lesions secondary to anti-VEGF activity. We additionally find that SF-OCT is able to image contrast from GNR alone or GNR in cells in tissue phantoms in vitro. In conclusion, while native OCT technologies have difficulty imaging GNR in the retina, PT-OCT can detect GNR in clinically relevant disease models in vivo and can detect physiological changes in LCNV lesions that are not detectable using standard OCT systems.