211 MRI of coronary vessel wall injury in a swine model of coronary intervention using an eletrostatically stabilized VSOP nanoparticle
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KeywordsRight Coronary Artery Coronary Vessel Wall Steady State Free Precession Imaging Unstable Lesion Specific Contrast Agent
Atherosclerosis is an inflammatory disease of the vessel wall with unstable lesions being associated with the presence of inflammatory cells, smooth muscle cell apoptosis, and the accumulation of LDL. Dextran coated superparamagnetic iron oxide (SPIO) nanoparticles (~20 nm) have been shown to allow for imaging of plaque resident macrophages approximately >24 h post intravenous injection. Citrate coated very small iron oxide (VSOP) nanoparticles (~7 nm) have been found useful for steady state aortic and coronary MR angiography (MRA) but also have been shown to accumulate in advanced aortic lesions in a rabbit model of atherosclerosis.
In this study we wanted to test the hypothesis whether the combined use of an extracellular matrix specific Gd-based contrast agent (BMS753951) together with a VSOP nanoparticle would allow the exclusive visualization of the pathologically altered coronary vessel wall in an animal model of coronary intervention.
Placement of MR-lucent prototype stents was performed in the proximal left coronary artery (LAD) of two female domestic swine (~30 kg). Following a one week normal diet, coronary MRA and delayed enhancement vessel wall imaging was performed using a 1.5 T Philips Achieva MR scanner. Immediately before the imaging session, animals were injected with 0.1 mmol/kg BMS753951, an elastin-binding low molecular weight Gd-based contrast agent (Bristol Myers Squibb, Billerica, MA). After localization of the heart, coronary MRA was performed using a steady state free precession imaging sequence. ~30 minutes post BMS753951 injection, delayed enhancement coronary wall imaging was performed with spatial resolution, slice thickness and image orientation maintained using an inversion recovery (IR) fast gradient echo technique. Subsequently, 60 μmol/kg VSOP (Ferropharm, Teltow, Germany) was injected and IR coronary MRA was performed with the inversion delay adjusted to minimize signal from myocardium. 45 minutes post VSOP administration, delayed enhancement vessel wall imaging was repeated with the inversion time adjusted to minimize signal from arterial blood. Immediately after the MRI session, animals were euthanized and hearts were harvested for histological examination.
We demonstrate the exclusive visualization of VSOP nanoparticles in the injured coronary vessel as a black rim artifact on coronary MRA. In addition, with the combined use of a matrix specific contrast agent, focal uptake of VSOP nanoparticles in the injured coronary vessel wall could be confirmed as displacement of the gadolinium signal seen after BMS753951 injection. In conclusion, VSOP nanoparticles have been shown to be useful for the detection pathological changes in the coronary vessel wall and potentially may be useful for the detection unstable lesions.
This article is published under license to BioMed Central Ltd.