title: Quantitative intravascular biological fluorescence-ultrasound imaging of coronary and peripheral arteries in vivo.
abstract: OBJECTIVE
  (i) to evaluate a novel hybrid near-infrared fluorescence-intravascular ultrasound (NIRF-IVUS) system in coronary and peripheral swine arteries in vivo; (ii) to assess simultaneous quantitative biological and morphological aspects of arterial disease.
  
  
  RESULTS
  Two 9F/15MHz peripheral and 4.5F/40MHz coronary near-infrared fluorescence (NIRF)-IVUS catheters were engineered to enable accurate co-registrtation of biological and morphological readings simultaneously in vivo. A correction algorithm utilizing IVUS information was developed to account for the distance-related fluorescence attenuation due to through-blood imaging. Corrected NIRF (cNIRF)-IVUS was applied for in vivo imaging of angioplasty-induced vascular injury in swine peripheral arteries and experimental fibrin deposition on coronary artery stents, and of atheroma in a rabbit aorta, revealing feasibility to intravascularly assay plaque structure and inflammation. The addition of ICG-enhanced NIRF assessment improved the detection of angioplasty-induced endothelial damage compared to standalone IVUS. In addition, NIRF detection of coronary stent fibrin by in vivo cNIRF-IVUS imaging illuminated stent pathobiology that was concealed on standalone IVUS. Fluorescence reflectance imaging and microscopy of resected tissues corroborated the in vivo findings.
  
  
  CONCLUSIONS
  Integrated cNIRF-IVUS enables simultaneous co-registered through-blood imaging of disease related morphological and biological alterations in coronary and peripheral arteries in vivo. Clinical translation of cNIRF-IVUS may significantly enhance knowledge of arterial pathobiology, leading to improvements in clinical diagnosis and prognosis, and helps to guide the development of new therapeutic approaches for arterial diseases.
authors.affiliation: Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany; Chair for Biological Imaging (CBI), Technische Universität München (TUM), Trogerstr. 9, 81675, Munich, Germany.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Bozhko
authors.affiliation: Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 025114, USA.|Cardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Osborn
authors.affiliation: Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany; Chair for Biological Imaging (CBI), Technische Universität München (TUM), Trogerstr. 9, 81675, Munich, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Rosenthal
authors.affiliation: Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 025114, USA.
authors.forename: Johan W
authors.initials: JW
authors.lastname: Verjans
authors.affiliation: Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 025114, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hara
authors.affiliation: Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany; Chair for Biological Imaging (CBI), Technische Universität München (TUM), Trogerstr. 9, 81675, Munich, Germany.|Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 025114, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kellnberger
authors.affiliation: Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany; Chair for Biological Imaging (CBI), Technische Universität München (TUM), Trogerstr. 9, 81675, Munich, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Wissmeyer
authors.affiliation: Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany; Chair for Biological Imaging (CBI), Technische Universität München (TUM), Trogerstr. 9, 81675, Munich, Germany.
authors.forename: Saak V
authors.initials: SV
authors.lastname: Ovsepian
authors.affiliation: Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 025114, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: McCarthy
authors.affiliation: Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany; Chair for Biological Imaging (CBI), Technische Universität München (TUM), Trogerstr. 9, 81675, Munich, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Mauskapf
authors.affiliation: Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany; Chair for Biological Imaging (CBI), Technische Universität München (TUM), Trogerstr. 9, 81675, Munich, Germany.
authors.forename: Ashley F
authors.initials: AF
authors.lastname: Stein
authors.affiliation: Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 025114, USA.
authors.forename: Farouc A
authors.initials: FA
authors.lastname: Jaffer
authors.affiliation: Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany; Chair for Biological Imaging (CBI), Technische Universität München (TUM), Trogerstr. 9, 81675, Munich, Germany.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
mesh_terms: D000465:Algorithms; D000818:Animals; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000473:pathology; D016491:Peripheral Vascular Diseases / Q000000981:diagnostic imaging* / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000473:pathology; D011817:Rabbits; D013050:Spectrometry, Fluorescence / Q000379:methods*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D015607:Stents; D013552:Swine; D018084:Ultrasonography, Interventional / Q000379:methods*
keywords: IVUS; NIRF; fluorescence imaging; molecular imaging