In vivo imaging of gold nanorod contrast agents using photothermal optical coherence tomography

Abstract

Photothermal optical coherence tomography (PT-OCT) has the potential to increase the molecular specificity of OCT for in vivo pre-clinical studies of cancer, in order to better understand drug uptake and treatment response. However, the use of PT-OCT to image contrast agents in vivo has yet to be demonstrated. Here, we characterize PT-OCT imaging of gold nanorod (GNR) contrast agents, and we further apply these techniques for in vivo imaging. The PT-OCT signal was characterized and compared to a numerical model of the bio-heat equation with respect to varying photothermal chop frequency, photothermal laser power, OCT image reflectivity, and concentration of GNRs. PT-OCT images were taken of GNR+ and GNR- solid agarose phantoms in capillary tubes, and 400 pM GNR matrigel injections into a mouse ear. Experimental PT-OCT data varied as predicted with closed form models of the bio-heat equation. Increasing the concentration of GNRs caused a linear increase in the PT-OCT signal, with GNR sensitivity as low as 7.5 pM compared to a scattering control (p<0.01). PT-OCT images in capillary tubes and the live mouse ear demonstrated an appreciable increase in signal in the presence of GNRs compared to controls. The demonstrated in vivo PT-OCT capabilities using GNR contrast agents is sufficient to image molecular expression, based on published molecular imaging studies employing GNR contrast agents in vivo. Therefore, this work demonstrates an important transition of PT-OCT to in vivo imaging, and marks the next step towards its use for in vivo molecular imaging.