Fully Integrated High-Speed Intravascular Optical Coherence Tomography/Near-Infrared Fluorescence Structural/Molecular Imaging In Vivo Using a Clinically Available Near-Infrared Fluorescence–Emitting 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 was to assess lipidrich inflamed plaques in vivo using fully integrated high-speed optical coherence tomography (OCT)/near-infrared fluorescence (NIRF) molecular imaging with a Food and Drug Administration-approved indocyanine green (ICG). Methods and Results-An integrated high-speed intravascular OCT/NIRF imaging catheter and a dual-modal OCT/NIRF system were constructed based on a clinical OCT platform. For imaging lipid-rich inflamed plaques, the Food and Drug Administration-approved NIRF-emitting ICG (2.25 mg/kg) or saline was injected intravenously into rabbit models with experimental atheromata induced by balloon injury and 12-to 14-week high-cholesterol diets. Twenty minutes after injection, in vivo OCT/NIRF imaging of the infrarenal aorta and iliac arteries was acquired only under contrast flushing through catheter (pullback speed up to ≤20 mm/s). NIRF signals were strongly detected in the OCT-visualized atheromata of the ICG-injected rabbits. The in vivo NIRF target-to-background ratio was significantly larger in the ICG-injected rabbits than in the saline-injected controls (P<0.01). Ex vivo peak plaque target-to-background ratios were significantly higher in ICG-injected rabbits than in controls (P<0.01) on fluorescence reflectance imaging, which correlated well with the in vivo target-to-background ratios (P<0.01; r=0.85) without significant bias (0.41). Cellular ICG uptake, correlative fluorescence microscopy, and histopathology also corroborated the in vivo imaging findings. Conclusions-Integrated OCT/NIRF structural/molecular imaging with a Food and Drug Administration -approved ICG accurately identified 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. (Circ Cardiovasc Interv. 2014;7:560-569.)

Lasing in blood

“…Previously it was thought that albumins are responsible for enhanced fluorescence in blood [8,38,41]. However, recent studies revealed that ICG might bind mainly to lipoproteins [2,8,36,42,43]. Indeed, our fluorescence measurement shows that lipoproteins bind more ICG and produce approximately three times stronger emission than albumins (Fig.…”

Erratum: Inflammatory processes in cardiovascular disease: a route to targeted therapies

“…Targeted molecular agents have been used to identify lipid-rich, metabolically active plaque in rabbit arteries 155,156 . Dual-modality OCT and near-infrared autofluorescence (NIRAF) using a specialized OCT-NIRAF catheter has been shown to be feasible and safe in humans and, indeed, NIRAF enhances the sensitivity to detect vulnerable thin-cap fibroatheroma 157 .…”

Interventional Cardiology

“…Studies have shown that combining angiography and intravascular ultrasound or optical coherence tomography can lead to far more information than 1 modality alone. 38,39 These fusion images are difficult to obtain and to process, but it is likely that in the future they can be real-time tools to guide diagnosis, understand pathophysiology, and guide PCI in complex anatomy. Combining imaging and hemodynamic data will also allow much more understanding of the pathophysiology of coronary disease.…”