While molecular and cellular imaging can be used to visualize the conventional morphology characteristics of vulnerable plaques, there is a need to monitor other physiological factors correlated with high rupture rates; a high M1 activated macrophage concentration is one such indicator of high plaque vulnerability. Here, we present a molecularly targeted contrast agent for intravascular photoacoustic (IVPA) imaging consisting of liposomes loaded with indocyanine green (ICG) J-aggregates with high absorption at 890 nm, allowing for imaging in the presence of blood. This “Lipo-ICG” was targeted to a biomarker of M1 activated macrophages in vulnerable plaques: folate receptor beta (FRβ). The targeted liposomes accumulate in plaques through areas of endothelial dysfunction, while the liposome encapsulation prevents nonspecific interaction with lipids and endothelium. Lipo-ICG specifically interacts with M1 activated macrophages, causing a spectral shift and change in the 890/780 nm photoacoustic intensity ratio upon breakdown of J-aggregates. This sensing mechanism enables assessment of the M1 activated macrophage concentration, providing a measure of plaque vulnerability. In a pilot in vivo study utilizing ApoE deficient mouse models of atherosclerosis, diseased mice showed increased uptake of FRβ targeted Lipo-ICG in the heart and arteries vs. normal mice. Likewise, targeted Lipo-ICG showed increased uptake vs. two non-targeted controls. Thus, we successfully synthesized a contrast agent to detect M1 activated macrophages in high risk atherosclerotic plaques and exhibited targeting both in vitro and in vivo. This biocompatible agent could enable M1 macrophage detection, allowing better clinical decision making in treatment of atherosclerosis.
Justin T. Harris, Diego S. Dumani, Jason R. Cook, Konstantin V. Sokolov, Stanislav Y. Emelianov, and Kimberly A. Homan, "Assessment of plaque vulnerability in atherosclerosis via intravascular photoacoustic imaging of targeted liposomal ICG J-aggregates (Conference Presentation)," Proc. SPIE 10064, Photons Plus Ultrasound: Imaging and Sensing 2017, 1006413 (Presented at SPIE BiOS: January 30, 2017; Published: 24 April 2017); https://doi.org/10.1117/12.2256537.5379284482001.
Conference Presentations are recordings of oral presentations given at SPIE conferences and published as part of the proceedings. They include the speaker's narration with video of the slides and animations. Most include full-text papers. Interactive, searchable transcripts and closed captioning are now available for 2018 presentations, with transcripts for prior recordings added daily.
Search our growing collection of more than 16,000 conference presentations, including many plenaries and keynotes.