Combined fluorescence lifetime imaging-optical coherence tomography for in vivo label-free assessment of high-risk atherosclerotic plaque

Multimodal optical coherence tomography (OCT) techniques are promising diagnostic tools to accurately assess highrisk atherosclerotic plaques. For rapid translation into clinical practice, the techniques should be performed through an intravascular imaging catheter without exogenous contrast agents under the same procedures as conventional imaging. In this study, we developed a label-free, multispectral, and catheter-based imaging system to simultaneously visualize the morphological and compositional information of coronary plaques by combining fluorescence lifetime imaging (FLIm) and OCT. Using a broadband hybrid optical rotary joint and a dual-modal imaging catheter, intravascular combined FLIm-OCT imaging was safely performed in an in vivo atherosclerotic coronary artery of atherosclerotic swine models without any imaging agent. Along with detailed coronary microstructure by OCT, the multispectral FLIm could accurately visualize fluorescence lifetime signature of key biochemical components of plaque in vivo (lipid, macrophage, and fibrous tissue) when comparing the corresponding histopathological stained-sections and ex vivo FLIm microscopy images. Especially, significant differences in fluorescence lifetime distribution were noted between lipid and macrophage (p < 0.0001), which were mostly indistinguishable with standalone OCT. Also, fluorescence lifetime distributions were significantly different according to plaque types (normal, fibrous vs. lipid-rich inflamed plaque, (p < 0.0001). With these statistical differences in plaque types and components, lipid distribution characterization and inflammation level estimation were provided in a pixel-by-pixel manner for the further assessment of the high-risk atherosclerotic plaque. This highly translatable imaging strategy can offer new opportunity for clinical intracoronary detection of high-risk plaques and will be a promising next-generation multimodal OCT technique.