Plasmonic Gold Nanostar-Enhanced Multimodal Photoacoustic Microscopy and Optical Coherence Tomography Molecular Imaging to Evaluate Choroidal Neovascularization

Although photoacoustic microscopy (PAM) and optical coherence tomography (OCT) allow visualization of the retinal microvasculature, distinguishing early neovascularization from adjacent vessels remains challenging. Herein, gold nanostars (GNSs) functionalized with an RGD peptide were utilized as multimodality contrast agents for both PAM and OCT. GNSs have great absorption and scattering characteristics in the near-infrared region where most vasculature and tissue generates a less intrinsic photoacoustic signal while having a small size, excellent biocompatibility in vivo, and great photostability under nanosecond pulsed laser illumination. This enabled visualization and differentiation of individual microvasculature in vivo using multimodal PAM and OCT imaging. Detailed three-dimensional imaging of GNSs was achieved in an important choroidal neovascularization model in living rabbits. Through the administration of GNSs, PA contrast increased up to 17-fold and OCT intensities increased 167%. This advanced molecular-imaging platform with GNSs provides a unique tool for detailed mapping of the pathogenesis of the microvasculature.