Intracoronary Structural-Molecular Imaging for Multitargeted Characterization of High-Risk Plaque
Authors: Sunwon Kim, Hyeong Soo Nam, Dong Oh Kang, Jeongmoo Han, Hyokee Kim, Joon Woo Song, Eun Jin Park, Ryeong Hyun Kim, Hyun Jung Kim, Jin Hyuk Kim, Sunki Lee, Young Su Kim, Pyoungjae Park, Man-Jong Baik, Hongki Yoo, Jin Won Kim
Journal: JAMA Cardiology (2025)

Importance Fluorescence lifetime imaging (FLIm) is a molecular imaging technique used to visualize the biochemical composition of atherosclerosis. Novel dual-modal imaging using optical coherence tomography (OCT)-FLIm has the potential to provide both microstructural and biocompositional information on coronary plaques; however, it needs validation for clinical application. Objective To investigate the clinical feasibility and safety of OCT-FLIm for characterizing plaque compositions in patients with coronary artery disease (CAD) undergoing revascularization therapy. Design, Setting, and Participants A prospective, open-label, single-center diagnostic feasibility study involving 40 patients with significant CAD requiring coronary revascularization. This first-in-human clinical study of the novel intracoronary OCT-FLIm imaging was conducted between February and August 2022. The analyses were performed from August 2022 to July 2023. Interventions An OCT-FLIm system with 2.6-F catheters was constructed. All patients underwent OCT-FLIm for target/culprit and nontarget/nonculprit lesions during coronary revascularization. Intravascular ultrasound imaging was performed for comparison. Main Outcomes and Measures The primary outcome was to assess the FLIm-derived molecular readouts of prespecified plaque compositions. The secondary outcome was the feasibility of OCT-FLIm in determining target/culprit plaque compositions across different subsets of atherosclerotic disease activity: (1) acute coronary syndrome (ACS) vs chronic stable angina (CSA) and (2) angiographic rapid disease progression vs nonprogressive controls. Results We prospectively enrolled 40 patients (mean [SD] age, 63.1 [8.1] years; 32 men [80.0%]), of whom 20 presented with ACS and 20 with CSA. OCT provided the structural features of plaques, and FLIm characterized the molecular signatures of atheroma compositions, including macrophages, healed plaques, superficial calcification, and fibrosis, in a reproducible manner. Fluorescence lifetime (FL) values of the plaque compositions correlated with findings from prior autopsy studies. Plaque inflammation was significantly greater in patients with ACS than those with CSA. The mean (SD) of inflammation-FL was 7.59 (0.96) nanoseconds for patients with ACS vs 6.46 (0.87) nanoseconds for patients with CSA ( P &amp;amp;lt; .001). The healed plaque phenotype was more prominently distributed in the segments of rapid disease progression than in nonprogressive controls. The mean (SD) healed plaque-FL was 5.31 (0.20) nanoseconds for the rapidly progressive lesions vs 4.81 (0.30) nanoseconds for the rapidly nonprogressive lesions ( P &amp;amp;lt; .001). All patients underwent OCT-FLIm safely without adverse clinical events. Conclusions and Relevance This diagnostic feasibility study found that an OCT-FLIm structural-molecular intracoronary imaging is clinically feasible and safe for the comprehensive characterization of human atheromas, supporting its potential role in the diagnosis and biological understanding of high-risk plaques.