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Jaffer, F.A.* ; Calfon, M.A.* ; Rosenthal, A. ; Mallas, G.* ; Razansky, R.N. ; Mauskapf, A.* ; Weissleder, R.* ; Libby, P.* ; Ntziachristos, V.

Two-dimensional intravascular near-infrared fluorescence molecular imaging of inflammation in atherosclerosis and stent-induced vascular injury.

J. Am. Coll. Cardiol. 57, 2516-2526 (2011)

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OBJECTIVES: This study sought to develop a 2-dimensional (2D) intravascular near-infrared fluorescence (NIRF) imaging strategy for investigation of arterial inflammation in coronary-sized vessels.BACKGROUND: Molecular imaging of arterial inflammation could provide new insights into the pathogenesis of acute myocardial infarction stemming from coronary atheromata and implanted stents. Presently, few high-resolution approaches can image inflammation in coronary-sized arteries in vivo.METHODS:A new 2.9-F rotational, automated pullback 2D imaging catheter was engineered and optimized for 360° viewing intravascular NIRF imaging. In conjunction with the cysteine protease-activatable imaging reporter Prosense VM110 (VisEn Medical, Woburn, Massachusetts), intra-arterial 2D NIRF imaging was performed in rabbit aortas with atherosclerosis (n =10) or implanted coronary bare-metal stents (n = 10, 3.5-mm diameter, day 7 post-implantation). Intravascular ultrasound provided coregistered anatomical images of arteries. After sacrifice, specimens underwent ex vivo NIRF imaging, fluorescence microscopy, and histological and immunohistochemical analyses. RESULTS: Imaging of coronary artery-scaled phantoms demonstrated 8-sector angular resolution and submillimeter axial resolution, nanomolar sensitivity to NIR fluorochromes, and modest NIRF light attenuation through blood. High-resolution NIRF images of vessel wall inflammation with signal-to-noise ratios >10 were obtained in real-time through blood, without flushing or occlusion. In atherosclerosis, 2D NIRF, intravascular ultrasound-NIRF fusion, microscopy, and immunoblotting studies provided insight into the spatial distribution of plaque protease activity. In stent-implanted vessels, real-time imaging illuminated an edge-based pattern of stent-induced arterial inflammation. CONCLUSIONS: A new 2D intravascular NIRF imaging strategy provides high-resolution in vivo spatial mapping of arterial inflammation in coronary-sized arteries and reveals increased inflammation-regulated cysteine protease activity in atheromata and stent-induced arterial injury.

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