title: Two-dimensional intravascular near-infrared fluorescence molecular imaging of inflammation in atherosclerosis and stent-induced vascular injury.
abstract: OBJECTIVE
  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.
authors.affiliation: Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. fjaffer@mgh.harvard.edu
authors.forename: Farouc A
authors.initials: FA
authors.lastname: Jaffer
authors.forename: Marcella A
authors.initials: MA
authors.lastname: Calfon
authors.forename: Amir
authors.initials: A
authors.lastname: Rosenthal
authors.forename: Georgios
authors.initials: G
authors.lastname: Mallas
authors.forename: R Nika
authors.initials: RN
authors.lastname: Razansky
authors.forename: Adam
authors.initials: A
authors.lastname: Mauskapf
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
mesh_terms: D000818:Animals; D002406:Catheterization, Peripheral / Q000295:instrumentation*; D003324:Coronary Artery Disease / Q000175:diagnosis*; D005456:Fluorescent Dyes; D007249:Inflammation / Q000175:diagnosis*; D011817:Rabbits; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation* / Q000379:methods*; D015607:Stents
chemical_list: D005456:Fluorescent Dyes