Two-Dimensional Intravascular Near-Infrared Fluorescence Molecular Imaging of Inflammation in Atherosclerosis and Stent-Induced Vascular Injury

source: ©2011 Journal of the American College of Cardiology

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.

Fig. 1 Schematic of the Constructed 2D NIRF Imaging System. The tip of the fiber contains a right angle coated prism that reflects the guide’s laser light into the artery wall and couples the subsequent fluorescent light back into the fiber. The fluorescent light is then directed to a dichroic beam splitter that selectively reflects it into a photomultiplier tube. The beam passes additional filters to minimize the parasitic signals of laser photons and autofluorescence. The inset shows the spectra of the 3 filters (I, II, III) used in the system. 2D = 2-dimensional; NIRF = near-infrared fluorescence.

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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F. A. Jaffer, M. A. Calfon, A. Rosenthal, G. Mallas, R. N. Razansky, A. Mauskapf, R. Weissleder, P. Libby, V. Ntziachristos, “Two-Dimensional Intravascular Near-Infrared Fluorescence Molecular Imaging of Inflammation in Atherosclerosis and Stent-Induced Vascular Injury,” J. Am. Coll. Cardiol., Vol. 57, pp. 2516-2526 (2011).