title: Fully integrated high-speed intravascular optical coherence tomography/near-infrared fluorescence structural/molecular imaging in vivo using a clinically available near-infrared fluorescence-emitting indocyanine green to detect inflamed lipid-rich atheromata in coronary-sized vessels.
abstract: BACKGROUND
  Lipid-rich inflamed coronary plaques are prone to rupture. The purpose of this study was to assess lipid-rich inflamed plaques in vivo using fully integrated high-speed optical coherence tomography (OCT)/near-infrared fluorescence (NIRF) molecular imaging with a Food and Drug Administration-approved indocyanine green (ICG).
  
  
  RESULTS
  An integrated high-speed intravascular OCT/NIRF imaging catheter and a dual-modal OCT/NIRF system were constructed based on a clinical OCT platform. For imaging lipid-rich inflamed plaques, the Food and Drug Administration-approved NIRF-emitting ICG (2.25 mg/kg) or saline was injected intravenously into rabbit models with experimental atheromata induced by balloon injury and 12- to 14-week high-cholesterol diets. Twenty minutes after injection, in vivo OCT/NIRF imaging of the infrarenal aorta and iliac arteries was acquired only under contrast flushing through catheter (pullback speed up to ≤20 mm/s). NIRF signals were strongly detected in the OCT-visualized atheromata of the ICG-injected rabbits. The in vivo NIRF target-to-background ratio was significantly larger in the ICG-injected rabbits than in the saline-injected controls (P<0.01). Ex vivo peak plaque target-to-background ratios were significantly higher in ICG-injected rabbits than in controls (P<0.01) on fluorescence reflectance imaging, which correlated well with the in vivo target-to-background ratios (P<0.01; r=0.85) without significant bias (0.41). Cellular ICG uptake, correlative fluorescence microscopy, and histopathology also corroborated the in vivo imaging findings.
  
  
  CONCLUSIONS
  Integrated OCT/NIRF structural/molecular imaging with a Food and Drug Administration -approved ICG accurately identified lipid-rich inflamed atheromata in coronary-sized vessels. This highly translatable dual-modal imaging approach could enhance our capabilities to detect high-risk coronary plaques.
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.).
authors: Sunki
authors: S
authors: Lee
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.).
authors: Min Woo
authors: MW
authors: Lee
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.).
authors: Han Saem
authors: HS
authors: Cho
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.).
authors: Joon Woo
authors: JW
authors: Song
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.).
authors: Hyeong Soo
authors: HS
authors: Nam
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.).
authors: Dong Joo
authors: DJ
authors: Oh
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.).
authors: Kyeongsoon
authors: K
authors: Park
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.). kjwmm@korea.ac.kr hyoo@hanyang.ac.kr woh1@kaist.ac.kr.
authors: Wang-Yuhl
authors: WY
authors: Oh
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.). kjwmm@korea.ac.kr hyoo@hanyang.ac.kr woh1@kaist.ac.kr.
authors: Hongki
authors: H
authors: Yoo
authors: From the Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea (S.L., J.W.S., D.J.O., J.W.K.); Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea (M.W.L., H.S.N., H.Y.); Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea (H.S.C., W.-Y.O.); and Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea (K.P.). kjwmm@korea.ac.kr hyoo@hanyang.ac.kr woh1@kaist.ac.kr.
authors: Jin Won
authors: JW
authors: Kim
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods; D005453:Fluorescence; D006801:Humans; D007208:Indocyanine Green / Q000008:administration & dosage*; D007249:Inflammation / Q000175:diagnosis*; D007259:Infrared Rays; D050356:Lipid Metabolism; D008264:Macrophages / Q000473:pathology; D023421:Models, Animal; D057054:Molecular Imaging / Q000379:methods; D058226:Plaque, Atherosclerotic / Q000175:diagnosis*; D011817:Rabbits; D041623:Tomography, Optical Coherence / Q000295:instrumentation* / Q000379:methods
chemical_list: D007208:Indocyanine Green
keywords: indocyanine green; molecular imaging; optical coherence tomography; plaque, atherosclerotic