First-in-Human Intracoronary Structural-Molecular Imaging for Multitargeted Characterization

초록

Background Fluorescence lifetime imaging (FLIm) visualizes detailed biochemical features of atherosclerosis. This first-in-human trial evaluated whether fully integrated optical coherence tomography-FLIm (OCT-FLIm) imaging could provide multitargeted biochemical information within plaque microstructure to characterize the high-risk atheroma in coronary arteries. Methods We developed a fully integrated OCT-FLIm system with a 2.6-F dual-modal catheter. In 215 pullbacks from 71 coronary arteries of 40 patients (mean age 63.1 ± 8.1 years) with acute coronary syndrome (ACS) or chronic stable angina (CSA), rapid OCT-FLIm were safely acquired during brief arterial flushing. Results Whereas OCT provided structural features, FLIm identified molecular signatures of plaque compositions, including macrophages, healed plaque, superficial calcification, and fibrosis. Composition-wise FLIm corroborated with previous autopsy study. Plaque inflammation was significantly higher in patients with ACS compared to those with CSA (P < 0.001) (Figure 1A and 1B). Healed plaques were more prominent in segments of rapid disease progression than in nonprogressive control subjects (P < 0.001) (Figure 1C and 1D), and correlated with inflammatory activity (P < 0.001). Ex vivo validation on fresh human arteries corroborated clinical OCT-FLIm findings. All patients safely underwent OCT-FLIm without adverse events. Conclusion Fully integrated OCT-FLIm structural-molecular intracoronary imaging was clinically safe and highly feasible for comprehensive characterization of human atheroma, offering new avenues for diagnosing and understanding high-risk plaque behavior.