High resolution photoacoustic microscopy molecular imaging of choroidal neovascularization using functionalized indocyanine green in living rabbits

Van Phuc Nguyen; Jeff Folz; Yanxiu Li; Jessica Henry; Wei Zhang; Xueding Wang; Yannis Paulus

doi:10.1117/12.2577692

5 March 2021 High resolution photoacoustic microscopy molecular imaging of choroidal neovascularization using functionalized indocyanine green in living rabbits

Van Phuc Nguyen, Jeff Folz, Yanxiu Li, Jessica Henry, Wei Zhang, Xueding Wang, Yannis Paulus

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Proceedings Volume 11631, Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XIX; 116310P (2021) https://doi.org/10.1117/12.2577692
Event: SPIE BiOS, 2021, Online Only

Abstract

Choroidal neovascularization (CNV) is a hallmark of advanced age-related macular degeneration and is a leading cause of irreversible vision loss and blindness in the world. There is a lack of imaging modalities that can detect CNV early. Photoacoustic microscopy (PAM) combines acoustic and optical imaging to create high-resolution images that can delineate microvasculature non-invasively and permit for visualization of CNV. However, to distinguish CNV from native microvasculature, molecular contrast agents can be applied to increase the sensitivity of PAM imaging. In this study, functionalized indocyanine green (ICG) with RGD ligands (ICG-RGD) was synthesized and applied to in vivo imaging of CNV in the rabbit retina using a custom-built high-resolution PAM imaging system. RGD ligands selective binds to integrins present in neovascularization. The CNV model was created in three New Zealand White rabbits via subretinal injection of human vascular endothelial grow factor (VEGF-165). Three-dimensional in vivo PAM images of CNV were acquired before and after intravenous injection of 400 µL ICG-RGD at a concentration of 2.5 mg/mL over a period of 14 days. In addition, color fundus photography and fluorescence imaging were also acquired. This enables visualization of the newly developed CNV as well as monitoring the changes in CNV over time. With the administration of ICG-RGD, PAM signal amplitudes enhanced up to 15.7-fold at day 1 post-injection and persisted up to 5 days. The PAM results were also confirmed by fluorescence imaging. Biosafety studies show no systemic toxicity of the ICG-RGD. These studies demonstrate the potential of molecular PAM imaging for the characterization of microvasculature pathologies.

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Van Phuc Nguyen, Jeff Folz, Yanxiu Li, Jessica Henry, Wei Zhang, Xueding Wang, and Yannis Paulus "High resolution photoacoustic microscopy molecular imaging of choroidal neovascularization using functionalized indocyanine green in living rabbits", Proc. SPIE 11631, Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XIX, 116310P (5 March 2021); https://doi.org/10.1117/12.2577692

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KEYWORDS

Indocyanine green

Photoacoustic microscopy

Image resolution

Molecular imaging

In vivo imaging

Luminescence

Visualization

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