title: Intracoronary dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular imaging with a clinical dose of indocyanine green for the assessment of high-risk plaques and stent-associated inflammation in a beating coronary artery.
abstract: Inflammation plays essential role in development of plaque disruption and coronary stent-associated complications. This study aimed to examine whether intracoronary dual-modal optical coherence tomography (OCT)-near-infrared fluorescence (NIRF) structural-molecular imaging with indocyanine green (ICG) can estimate inflammation in swine coronary artery.
  
  
  
  After administration of clinically approved NIRF-enhancing ICG (2.0 mg/kg) or saline, rapid coronary imaging (20 mm/s pullback speed) using a fully integrated OCT-NIRF catheter was safely performed in 12 atheromatous Yucatan minipigs and in 7 drug-eluting stent (DES)-implanted Yorkshire pigs. Stronger NIRF activity was identified in OCT-proven high-risk plaque compared to normal or saline-injected controls (P = 0.0016), which was validated on ex vivo fluorescence reflectance imaging. In vivo plaque target-to-background ratio (pTBR) was much higher in inflamed lipid-rich plaque compared to fibrous plaque (P < 0.0001). In vivo and ex vivo peak pTBRs correlated significantly (P < 0.0022). In vitro cellular ICG uptake and histological validations corroborated the OCT-NIRF findings in vivo. Indocyanine green colocalization with macrophages and lipids of human plaques was confirmed with autopsy atheroma specimens. Two weeks after DES deployment, OCT-NIRF imaging detected strong NIRF signals along stent struts, which was significantly higher than baseline (P = 0.0156). Histologically, NIRF signals in peri-strut tissue co-localized well with macrophages.
  
  
  
  The OCT-NIRF imaging with a clinical dose of ICG was feasible to accurately assess plaque inflammation and DES-related inflammation in a beating coronary artery. This highly translatable dual-modal molecular-structural imaging strategy could be relevant for clinical intracoronary estimation of high-risk plaques and DES biology.
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, 80, Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Sunwon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Min Woo
authors.initials: MW
authors.lastname: Lee
authors.affiliation: Department of Mechanical Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Tae Shik
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, 80, Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Joon Woo
authors.initials: JW
authors.lastname: Song
authors.affiliation: Department of Biomedical Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Hyeong Soo
authors.initials: HS
authors.lastname: Nam
authors.affiliation: Department of Mechanical Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Han Saem
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Mechanical Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Sun-Joo
authors.initials: SJ
authors.lastname: Jang
authors.affiliation: Department of Mechanical Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Jiheun
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, 80, Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Dong Joo
authors.initials: DJ
authors.lastname: Oh
authors.affiliation: Department of Mechanical Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Dae-Gab
authors.initials: DG
authors.lastname: Gweon
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, 80, Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.|Department of Legal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Daejeon, Republic of Korea.
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Mechanical Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea kjwmm@korea.ac.kr hyoo@hanyang.ac.kr woh1@kaist.ac.kr.
authors.forename: Wang-Yuhl
authors.initials: WY
authors.lastname: Oh
authors.affiliation: Department of Biomedical Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea kjwmm@korea.ac.kr hyoo@hanyang.ac.kr woh1@kaist.ac.kr.
authors.forename: Hongki
authors.initials: H
authors.lastname: Yoo
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, 80, Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea kjwmm@korea.ac.kr hyoo@hanyang.ac.kr woh1@kaist.ac.kr.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000818:Animals; D003324:Coronary Artery Disease; D003331:Coronary Vessels; D054855:Drug-Eluting Stents; D006801:Humans; D007208:Indocyanine Green; D007249:Inflammation; D057054:Molecular Imaging; D015607:Stents; D013552:Swine; D041623:Tomography, Optical Coherence
chemical_list: D007208:Indocyanine Green
keywords: Atherosclerosis; Imaging; Inflammation; Plaque; Stents