Photoactivation is a promising theranostic tool to image and stabilize the atherosclerotic plaque by apoptosis induction in macrophages or other vascular cells; however, lack of effective drugs and mechanistic understanding hinder its clinical application for cardiovascular disease. Here, we developed the macrophage targeted photosensitizer delivery strategy and demonstrated that imaging assisted light activation reduced inflammation and burden of atherosclerotic plaques. Mechanistically, targeted photoactivation induced autophagy and increased MerTK expression in carotid atheroma as early as 1 day, and had 2-fold increase in macrophage-associated apoptotic cells, indicating efferocytosis enhancement. This multifunctional photoactivatable theranostic strategy could confer a promising tool for high-risk plaques.
Intravascular optical coherence tomography-fluorescence lifetime imaging (OCT-FLIm) provides co-registered structural and biochemical information of atherosclerotic plaques in a label-free manner. For intuitive image interpretation of OCT-FLIm, herein, we present a machine learning classifier where key biochemical components (lipids, lipids+macrophages, macrophages, fibrotic, and normal) related to plaque destabilization are characterized based on the combination of multispectral FLIm parameters and convolutional OCT features. Using dataset from in vivo atheromatous swine models, the classification accuracy was >92% for each plaque component according the five-fold cross validation. This highly translatable imaging strategy will open a new avenue for clinical intracoronary assessment of high-risk plaques.
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.
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