Abstract 18785: In vivo Dual-Modality Molecular Imaging of Atheroma Inflammation via An Integrated Near-infrared Fluorescence and Optical Frequency Domain Imaging System
Background: The aim of this study was to simultaneously assess in vivo inflammatory protease activity, macrophage content, and plaque anatomy using a new integrated intravascular optical frequency domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging system.
Methods: A new integrated, fully co-registered OFDI/NIRF catheter was constructed using a single fiber OFDI clinical platform. For imaging cysteine protease activity in experimental atheroma of cholesterol-fed balloon-injured rabbits (n=8), an activatable NIRF agent targeting cathepsin B (CatB) (n=7, VM110) or saline (n=1) was injected intravenously. Twenty-four hours thereafter, the OFDI/NIRF catheter was inserted and rapidly pulled back (5–10 mm/sec) across aortoiliac vessels, with saline flushing and/or balloon occlusion. In vivo NIRF plaque target-to-background ratios (TBRs) were analyzed. Plaque macrophages were imaged using the standard deviation of the OFDI signal. Resected vessels underwent ex vivo fluorescence imaging (FRI) and histopathological analyses.
Results: In VM110-injected rabbits, focal NIRF signal was detected in OFDI-visualized atheroma, including microscopic plaques (Figure). The in vivo NIRF plaque protease TBR was significantly greater than in plaques from the saline-injected rabbit (n=98 plaques analyzed, 4.4 vs. 1.7, p=0.001). Depth-corrected macrophage content derived from OFDI correlated significantly with the CatB NIRF protease signal (r=0.68, p=0.001). The in vivo and ex vivo peak plaque TBRs also correlated well (r=0.70, p=0.008). Histopathology and immunoblotting revealed colocalization of the NIRF signal with CatB in atheromata.
Conclusions: A new single NIRF-OFDI catheter approach simultaneously assesses molecular and cellular plaque inflammation and plaque anatomy in rapid fashion in vivo. This dual modality approach may provide an integrated molecular and structural imaging approach to identify high-risk coronary plaques.
- © 2010 by American Heart Association, Inc.