Abstract
Photothermal optical coherence tomography (PT-OCT) is a potentially powerful tool for molecular imaging. Here, we characterize PT-OCT imaging of gold nanorod (GNR) contrast agents in phantoms, and we apply these techniques for in vivo GNR imaging. The PT-OCT signal was compared to the bio-heat equation in phantoms, and in vivo PT-OCT images were acquired from subcutaneous 400 pM GNR Matrigel injections into mice. Experiments revealed that PT-OCT signals varied as predicted by the bio-heat equation, with significant PT-OCT signal increases at 7.5 pM GNR compared to a scattering control (p < 0.01) while imaging in common path configuration. In vivo PT-OCT images demonstrated an appreciable increase in signal in the presence of GNRs compared to controls. Additionally, in vivo PT-OCT GNR signals were spatially distinct from blood vessels imaged with Doppler OCT. We anticipate that the demonstrated in vivo PT-OCT sensitivity to GNR contrast agents is sufficient to image molecular expression in vivo. Therefore, this work demonstrates the translation of PT-OCT to in vivo imaging and represents the next step towards its use as an in vivo molecular imaging tool.
Highlights
In vivo molecular imaging is widely used in pre-clinical studies of the diseases that cause the greatest burdens of morbidity and mortality in the developed world [1]
We have demonstrated Photothermal optical coherence tomography (PT-Optical coherence tomography (OCT)) of highly absorbing gold nanorod (GNR) contrast agents in the near infrared wavelength region, including validation in phantoms and feasibility studies in vivo
We characterized the photothermal signal with the bio-heat equation, and directly compared modeled and experimental PT-OCT data
Summary
In vivo molecular imaging is widely used in pre-clinical studies of the diseases that cause the greatest burdens of morbidity and mortality in the developed world (e.g., cancer, cardiovascular disease, diabetes, etc.) [1]. Microscopy, including confocal and multiphoton microscopy, has been the standard for high resolution molecular imaging in live cells and tissues. These microscopy techniques suffer from relatively shallow imaging depths. Optical coherence tomography (OCT) fills a niche between high resolution microscopy and whole body imaging techniques with cellular-level resolution and penetration depths in tissue that exceed the imaging depths of microscopy. This three-dimensional, non-invasive imaging technique provides an especially attractive scale for monitoring mouse models of disease. Augmenting standard OCT images with sensitive and specific molecular contrast represents an area of significant interest
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