Abstract

Despite exciting advances in structural intravascular imaging [intravascular ultrasound (IVUS) and optical coherence tomography (OCT)] that have enabled partial assessment of atheroma burden and high-risk features associated with acute coronary syndromes, structural-based imaging modalities alone do not comprehensively phenotype the complex pathobiology of atherosclerosis. Near-infrared fluorescence (NIRF) is an emerging molecular intravascular imaging modality that allows for in vivo visualization of pathobiological and cellular processes at atheroma plaque level, including inflammation, oxidative stress, and abnormal endothelial permeability. Established intravascular NIRF imaging targets include macrophages, cathepsin protease activity, oxidized low-density lipoprotein and abnormal endothelial permeability. Structural and molecular intravascular imaging provide complementary information about plaque microstructure and biology. For this reason, integrated hybrid catheters that combine NIRF-IVUS or NIRF-OCT have been developed to allow co-registration of morphological and molecular processes with a single pullback, as performed for standalone IVUS or OCT. NIRF imaging is approaching application in clinical practice. This will be accelerated by the use of FDA-approved indocyanine green (ICG), which illuminates lipid- and macrophage-rich zones of permeable atheroma. The ability to comprehensively phenotype coronary pathobiology in patients will enable a deeper understanding of plaque pathobiology, improve local and patient-based risk prediction, and usher in a new era of personalized therapy.

Highlights

  • In 1989, Muller et al [1] proposed the term “vulnerable plaque” to describe coronary artery plaques prone to rupture and cause acute myocardial infarction or sudden cardiac death

  • Using rabbit model and hybrid Near-infrared fluorescence (NIRF)-optical coherence tomography (OCT) intravascular imaging, our group was able to demonstrate that drug eluting stents (DES) showed increased fibrin deposition and fibrin persistence when compared to bare metal stents (BMS), both at day 7 and day 28 [57]

  • This study may pave the way for future human intracoronary NIRF-OCT using indocyanine green (ICG) to image pathobiological aspects of coronary atherosclerosis

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Summary

INTRODUCTION

In 1989, Muller et al [1] proposed the term “vulnerable plaque” to describe coronary artery plaques prone to rupture and cause acute myocardial infarction or sudden cardiac death. It is noteworthy that molecular and anatomical intravascular imaging provide complementary information about plaque structure and biology This motivated the development of multimodal NIRF hybrid catheter systems that combines NIRF with either OCT or IVUS, for both molecular-structural co-registration, and improved quantification of NIR fluorescence signals. Ex vivo imaging of rabbit aortas using intravascular NIRF catheter, showed localization of LO1-750 in atheroma lesions This agent represents a translatable platform for future use in human subjects to enable quantifying plaque oxidative stress. Using rabbit model and hybrid NIRF-OCT intravascular imaging, our group was able to demonstrate that drug eluting stents (DES) showed increased fibrin deposition and fibrin persistence when compared to bare metal stents (BMS), both at day 7 and day 28 [57] This finding revealed the limitations of standalone OCT imaging, which cannot distinguish between healthy endothelial cell coverage vs impaired healing demarcated by fibrin deposition.

Limitation
CONCLUSION AND FUTURE DIRECTIONS
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