Abstract 612: In vivo Molecular-Structural Imaging of Endothelial Permeability and Inflammation Assesses Injury Following Stent Implantation

Background: Local injury after stent implantation is implicated in restenosis, however the role of vascular permeability and early inflammation has not been assessed in vivo. We investigated the stent-induced vessel wall permeability and protease inflammatory response under different clinical interventional stent deployment methods. Methods: Non-overlapping bare-metal stents (2.25x8mm) were implanted in normal rabbit iliac arteries (n=3 animals, n=9 total stents) under the following conditions: (i) angioplasty balloon then stent implantation (1.1:1 stent:artery diameter ratio); (ii) cutting balloon then 1.1:1 stent; (iii) angioplasty balloon then 1.3:1 stent (oversized). Based on IVUS, stents were post-dilatated as needed. Serial intravascular near-infrared fluorescence (NIRF) - optical coherence tomography (OCT) imaging was performed immediately after stent implantation with a NIRF molecular imaging agent for impaired endothelial permeability (indocyanine green (ICG)), and 2 and 6 weeks later with a NIRF plaque inflammatory protease activity reporter (ProSense VM110). Quantitation of stent NIRF imaging agent concentration was enabled by OCT-based distance correction. In vivo imaging results were corroborated by ex vivo fluorescence reflectance imaging, fluorescence microscopy, and histopathology. Results: IVUS-guided stent implantation showed the expected protocol stent:reference vessel diameter ratios: 1.05±0.05 (mean±SD), 1.1:1 percutaneous transluminal angioplasty (PTA) group; 1.07±0.05, 1.1:1 cutting balloon group; and 1.29±0.09, 1.3:1 PTA group. In vivo ICG NIRF-OCT imaging at stent implantation demonstrated that NIRF ICG signal 30 min after stent implantation was higher when more aggressive vessel injury was performed (1.3:1 PTA and 1.1:1 cutting, p<0.01). While Prosense NIRF stent inflammation was not significantly different among the groups at 2 or 6 weeks, the baseline NIRF ICG endothelial permeability signal modestly correlated with 2-week NIRF stent inflammation (r=0.43). Conclusion: In vivo ICG NIRF imaging of endothelial permeability at the time of coronary stent implantation may allow a point-of-care estimation of subsequent stent inflammation and the risk of future stent restenosis.