Abstract
1538
Objectives: Background and Aim: Current clinical intravascular imaging modalities have limitations on the evaluation of plaque morphology and pathobiology. This study aims to assessment the application of hybrid intravascular imaging which contains a dual-probe catheter includes intravascular ultrasound (IVUS) and intravascular photoacoustic (IVPA) probe on the rabbit atherosclerotic models via RGDfk peptide targeted nanoparticles probe.
Methods: The dual-modality probe is based on a 39 MHz ring-shaped ultrasound (US) transducer which detects both US echoes and laser-generated photoacoustic (PA) signals. The targeted nanoparticles probe was constructed by coupling human serum albumin (HSA) coated nanoparticles and indole cyanide green (ICG) to RGDfk peptide(HAS-ICG-RGD). MTT and flow cytometric analysis were performed to detect the effects of HAS-ICG-RGD on cell proliferation, cell cycle and apoptosis in human vascular endothelial cells (HVECs). Immunofluorescence staining and Prussian blue staining were applied respectively to investigate the affinity of RGDfk peptide. The atherosclerosis model was induced in New Zealand white rabbits by abdominal aorta balloon de-endothelialization and atherogenic diet for 16 weeks. The plaque areas in abdominal artery were detected by ultrasound imaging and Oil Red O staining. In vivo hybrid intravascular imaging of atherosclerotic plaque in abdominal aorta were carried out at different time points after intravenous injection of nanoparticles.
Results: The HAS-ICG-RGD nanoparticles with hydrodynamic diameter of 20nm ± 0.4nm exhibited good imaging properties, high stability, low immunogenicity and little cytotoxicity. With the excitation of 780nm wavelength, IVUS/IVPA imaging system can obtain clear structure character of atherosclerosis plaques, and can capture the photoacoustic signal of HAS-ICG-RDG nanoparticles, revealed that HAS-ICG-RGD nanoparticles were successfully applied to visualize atherosclerotic vulnerable plaque in the rabbit abdominal aorta. With the excitation of 1700nm wavelength, IVUS/IVPA imaging system can obtain clear structure character of atherosclerosis plaques, and can capture the photoacoustic signal of lipid composition. Immunohistochemical staining confirmed that HAS-ICG-RGD nanoparticles were well co-localized within the atherosclerosis plaques.
Conclusions: With the combination of targeted nanoparticles probe, the dual-probe designed hybrid intravascular imaging probe can provides structure information and inflammatory component information of atherosclerotic plaques in rabbit abdominal artery simultaneously, which demonstrates the imaging ability of the hybrid intravascular imaging system via RGDfk peptide targeted nanoparticles probe, implying future clinical applications. Key words: atherosclerosis, hybrid intravascular imaging, intravascular ultrasound, intravascular photoacoustic, RGDfk peptide, nanoparticles probe.