In vivo photothermal optical coherence tomography of endogenous and exogenous contrast agents in the eye

Abstract

Optical coherence tomography (OCT) has become a standard-of-care in retinal imaging. OCT allows non-invasive imaging of the tissue structure but lacks specificity to contrast agents that could be used for in vivo molecular imaging. Photothermal OCT (PT-OCT) is a functional OCT-based technique that has been developed to detect absorbers in a sample. We demonstrate in vivo PT-OCT in the eye for the first time on both endogenous (melanin) and exogenous (gold nanorods) absorbers. Pigmented mice and albino mice (n = 6 eyes) were used to isolate the photothermal signal from the melanin in the retina. Pigmented mice with laser-induced choroidal neovascularization lesions (n = 7 eyes) were also imaged after a systemic injection of gold nanorods to observe their passive accumulation in the retina. This experiment demonstrates the feasibility of PT-OCT to image the distribution of both endogenous and exogenous absorbers in the mouse retina.

Imaging Melanin Distribution in the Zebrafish Retina Using Photothermal Optical Coherence Tomography

“…In the past, PT-OCT of melanin in the eye had only been tested by comparing WT mice to albino mice imaged during separate experiments. 28 Thus, the current study provided a more robust validation of PT-OCT sensitivity to melanin within a single retina. We further demonstrated that the PT-OCT signal for pigmented ROIs increases linearly with laser power, as predicted by theory.…”

“…PT-OCT is a functional OCT technique that detects optical absorbers such as gold nanoparticles 25 or indocyanine green 35 and has recently been demonstrated in the eye for the first time. 28 In this study, we used PT-OCT to image the distribution of melanin in the zebrafish retina. Melanin is naturally present in the RPE, and changes in retinal pigmentation are observed in multiple eye conditions, such as AMD, 6 albinism, 36 and retinitis pigmentosa.…”

“… 26 More recently, PT-OCT of melanin has been demonstrated in vivo in skin 27 and in the mouse eye. 28 The PT-OCT signal is linearly proportional to the absorption coefficient of a sample and can thus be used to evaluate relative concentrations of a contrast agent. 24 …”

Directional optical coherence tomography reveals melanin concentration-dependent scattering properties of retinal pigment epithelium

“…21,22 Photothermal OCT (PTOCT) is another functional extension of OCT, based on the photothermal effect, which enables the detection of the optical absorbers in tissues. By taking advantage of the strong absorption in IR by melanin, Lapierre-Landry et al 23,24 demonstrated the capability of PTOCT to image melanin distribution in mice and zebrafish retina, and the migration of melanin within RPE in response to dark and light adaptation.…”

A Spectral De-mixing Model for Triplex In Vivo Imaging of Optical Coherence Tomography Contrast Agents

“…fluorescent markers), which enable localization of cell types, patterns of protein expression, and imaging of lymph/blood vessels 2 . The majority of previous work has focused on use of a single contrast agent, such as absorptive dyes 3 , microbeads 4,5,6 , and gold nanoparticles 7,8,9 . Two-plex imaging of gold nanoparticles has been demonstrated, but only under the assumption that each voxel contained a single type of contrast agent 10,11 .…”