In Vivo Near-Infrared Fluorescence Imaging of Atherosclerosis Using Local Delivery of Novel Targeted Molecular Probes

Marie-Jeanne Bertrand,Mehdi Arbabi-Ghahroudi,Teodora Mihalache-Avram,Éric Rhéaume,Martin Sirois,Foued Maafi,David Busseuil,Maxime Abran,Philippe L L’Allier,Jean-Claude Tardif,Pier-Luc Tardif,Feng Ni,Pascale Geoffroy,Abedelnasser Abulrob,Nolwenn Merlet,Frédéric Lesage

doi:10.1038/s41598-019-38970-4

Marie-Jeanne Bertrand, Mehdi Arbabi-Ghahroudi + Show 14 more

Open Access

https://doi.org/10.1038/s41598-019-38970-4

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Abstract

This study aimed to evaluate the feasibility and accuracy of a technique for atherosclerosis imaging using local delivery of relatively small quantities (0.04–0.4 mg/kg) of labeled-specific imaging tracers targeting ICAM-1 and unpolymerized type I collagen or negative controls in 13 rabbits with atheroma induced by balloon injury in the abdominal aorta and a 12-week high-cholesterol diet. Immediately after local infusion, in vivo intravascular ultrasonography (IVUS)-NIRF imaging was performed at different time-points over a 40-minute period. The in vivo peak NIRF signal was significantly higher in the molecular tracer-injected rabbits than in the control-injected animals (P < 0.05). Ex vivo peak NIRF signal was significantly higher in the ICAM-1 probe-injected rabbits than in controls (P = 0.04), but not in the collagen probe-injected group (P = 0.29). NIRF signal discrimination following dual-probe delivery was also shown to be feasible in a single animal and thus offers the possibility of combining several distinct biological imaging agents in future studies. This innovative imaging strategy using in vivo local delivery of low concentrations of labeled molecular tracers followed by IVUS-NIRF catheter-based imaging holds potential for detection of vulnerable human coronary artery plaques.

Highlights

Near-infrared fluorescence (NIRF) is an innovative high-resolution imaging technology that allows visualization of inflammatory processes at the cellular level using target-specific labeled tracers, enabling atherosclerosis detection at early stages of the disease[9,10,11]
In vivo intravascular ultrasound (IVUS)-near-infrared fluorescence (NIRF) imaging was performed at week 12 following local delivery of labeled NIRF molecular agents targeting ICAM-1 and unpolymerized type I collagen at the injured site of the abdominal aorta (Fig. 1)
We demonstrated the feasibility of local delivery of relatively small quantities of NIRF targeted tracers for in vivo imaging of both morphological and biological biomarkers of atherosclerotic plaques using a fully-integrated real-time intravascular bimodal IVUS-NIRF imaging catheter

Summary

Introduction

Near-infrared fluorescence (NIRF) is an innovative high-resolution imaging technology that allows visualization of inflammatory processes at the cellular level using target-specific labeled tracers, enabling atherosclerosis detection at early stages of the disease[9,10,11]. The discrepancy of ICG specificity observed between rabbits and human atherosclerotic plaque components could result from the short systemic half-life of ICG and the low concentration administered to subjects prior to endarterectomy[22]. This preliminary study aimed at overcoming the present limitations of NIRF imaging and addressing the need for a clinically available intravascular molecular imaging modality to accurately and safely target both inflammation and specific atherosclerotic plaque components, an unmet need in clinical practice. The feasibility of a technique of local delivery of imaging agents was evaluated using two newly engineered near-infrared labeled molecular probes to image plaque composition and inflammation using a custom bimodal intravascular ultrasound (IVUS) – NIRF imaging catheter system in atherosclerotic rabbit aortas

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