Abstract 18568: Intravascular Near-Infrared Fluorescence Molecular Imaging of Atherosclerosis and Coronary Stent-Induced Inflammation Using a Novel Two-Dimensional Imaging Catheter
Background: The aim of this study was to 1) develop and validate a 2D NIRF imaging catheter using coronary arterial-scale phantoms 2) generate accurate in vivo 2D NIRF maps of atheroma and stent vascular inflammation and 3) provide new spatial insight into augmented cathepsin activity in atherosclerosis and stent-induced vascular injury.
Methods: A new intravascular NIRF imaging catheter with automated pullback capabilities was developed. Phantom studies were performed in saline and blood-like media. New Zealand white rabbits (n=16) underwent 1) aortic balloon injury followed by 8 weeks cholesterol-diet or 2) aortic balloon injury followed by bare metal stenting and 1 week recovery. One day prior to imaging, rabbits received IV injection of saline or cysteine protease activatable imaging agent (VM110, ex/em 750/770nm) at 8 weeks (atherosclerotic) or 7 days (stented animals). Angiography and IVUS were performed, followed by multiple automated NIRF catheter pullbacks across atheroma or stents in the aorta. Alignment of angio, IVUS and NIRF images were performed. Resected aorta underwent ex vivo correlation using microscopic and immunoblot analyses.
Results: Phantom studies of NIRF catheter revealed detection of fluorochrome (range 10nM- 50 uM) up to 3 mm distance from target, with signal decay inverse to square of distance. In vivo high-resolution imaging using the NIRF catheter to generate 2D maps demonstrated eccentric protease signals that co-registered to eccentric plaques detected by IVUS. In stent group, high NIRF protease signal occurred at stent edges, consistent with balloon overhang injury. In vivo lesional target-to-background ratios (TBR) were higher in VM110-injected animals compared to saline (mean TBR 3.9 vs 1.14, p<0.05). Microscopic and immunoblot analyses demonstrated strong NIRF signal, cathepsin B and macrophages in plaque and within stents.
Conclusions: We present a new high resolution 2D rotational NIRF catheter for imaging of intravascular inflammation. Co-registration with IVUS revealed abundant protease activity in atheroma and edges of coronary stents. This integrated multimodal strategy offers a highly translatable approach to investigate vascular inflammation in coronary-sized arteries.
- © 2010 by American Heart Association, Inc.