A Fully Integrated High-Speed Intravascular OFDI-NIRF Structural-Molecular Imaging in vivo With a FDA-Approved Indocyanine Green to Detect Inflamed, Lipid-Rich Atheromata in Coronary Sized Vessels

Abstract

Background: Lipid-rich, inflamed coronary plaques are prone to rupture. The purpose of this study is to in vivo assess lipid-rich, inflamed plaque via a fully integrated, high-speed OFDI (optical frequency domain imaging)-NIRF (near-infrared fluorescence) structural-molecular imaging with a FDA-approved indocyanine green (ICG).Methods: An integrated, high-speed intravascular OFDI-NIRF imaging catheter and a dual-modal OFDI-NIRF system was constructed based on a clinical OFDI platform. For imaging lipid-rich inflamed plaque, a FDA approved NIRF emitting ICG (2.0 mg/kg) or saline was injected intravenously in experimental atheromatous rabbits induced by balloon injury and a high-cholesterol diet for 12 weeks. Twenty minutes later, OFDI-NIRF imaging in vivo of infrarenal aorta and iliac artery was acquired only under saline flushing through a catheter (pullback speed upto 20 mm/sec).Results: NIRF signals were strongly detected in OFDI-visualized atheromata of ICG injected rabbits. The in vivo NIRF target-to-background ratio (TBR) was significantly greater in the ICG-injected rabbits than the saline-injected control rabbits (p<0.001). By fluorescence reflectance imaging, ex vivo mean plaque TBRs were significantly higher in ICG injected rabbits than controls (p<0.001) (Figure), which correlated well with in vivo plaque TBRs (p<0.01). ICG cell uptake, correlative fluorescence microscopy, and histopathology corroborated the in vivo imaging findings (Figure).Conclusions: An integrated OFDI-NIRF structural-molecular imaging with a FDA-approved ICG was able to accurately identify lipid-rich, inflamed atheromata in coronary sized vessels. This highly translatable dual-modal imaging approach could enhance our capabilities to detect high-risk coronary plaques.