..................................................................................................................................................................................... ..................................................................................................................................................................................... BASIC SCIENCE 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 Sunwon Kim 1† , Min Woo Lee 2† , Tae Shik Kim 3† , Joon Woo Song 1 , Hyeong Soo Nam 2 , Han Saem Cho 3 , Sun-Joo Jang 3 , Jiheun Ryu 3 , Dong Joo Oh 1 , Dae-Gab Gweon 3 , Seong Hwan Park 1,4 , Kyeongsoon Park 5 , Wang-Yuhl Oh 3‡ * , Hongki Yoo 2‡ * , and Jin Won Kim 1‡ * 1 Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, 80, Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea; 2 Department of Biomedical Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea; 3 Department of Mechanical Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea; 4 Department of Legal Medicine, Korea University College of Medicine, Seoul, Republic of Korea; and 5 Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Daejeon, Republic of Korea Received 20 May 2015; revised 19 October 2015; accepted 10 December 2015 Aims 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. Methods and results 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 ¼ 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 colo- calization 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 high- er than baseline (P ¼ 0.0156). Histologically, NIRF signals in peri-strut tissue co-localized well with macrophages. Conclusion 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. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Atherosclerosis † Inflammation † Imaging † Plaque † Stents † Contributed equally. ‡ Shared senior authorship. * Corresponding author. Tel: +82 02 2626 3021, Fax: +82 2 863 1109, Email: kjwmm@korea.ac.kr (J.W.K.); Tel: +82 2 2220 2323, Fax: +82 2 2220 5943, Email: hyoo@hanyang.ac.kr (H.Y.); Tel: +82 42 350 3237, Fax: +82 42 350 5237, Email: woh1@kaist.ac.kr (W-Y.O) Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2016. For permissions please email: journals.permissions@oup.com. doi:10.1093/eurheartj/ehv726 European Heart Journal (2016) 37, 2833–2844 ; online publish-ahead-of-print 18 January 2016 Downloaded from https://academic.oup.com/eurheartj/article-abstract/37/37/2833/2469927 by guest on 30 May 2020