Abstract 589: Quantitative Molecular Imaging of Atherosclerotic Aortic Endothelial Dysfunction With Perfluorocarbon (19F) Nanoparticle Magnetic Resonance Imaging and Spectroscopy
Disturbed endothelial barrier function in atherosclerosis has been detected by MRI by imaging gadolinium leakage into the vascular interstitium but not yet quantified. Alternatively, we propose that the unique, no background 19F signal from crown ether perfluorocarbon-core nanoparticles (NP: ~250 nm) might both visualize and quantify endothelial disruption in advanced atherosclerosis.
Methods: Five NZW rabbits were fed a high fat diet for 9 –12 months (cholesterol: 1200 –1700 mg/dL). Fluorescently-labeled, nontargeted NP were injected (2 ml/kg) intravenously into the ear vein. After circulation in vivo for 1, 6 or 24 hours, aortas were excised for 19F MRI and spectroscopy (Varian 11.74 T scanner); and whole mount fluorescence imaging (Xenogen IVIS system). A perfluorooctyl bromide calibration standard enabled MRS-based quantification of NP concentration in each imaged voxel.
Results: MRI (19F/1H overlay) revealed abundant 19F signal from intact NP that were localized heterogeneously in the plaque interstitium (A), but not in unaffected areas, and distinct from macrophage uptake, according to high resolution fluorescence microscopy. The average tissue concentration of NP calculated from MR spectroscopy (B) was 2.36±0.42 billion/g aorta. Fluorescence imaging (C) confirmed the presence of NP.
Conclusion: Intact nontargeted NP rapidly penetrate the leaky endothelial barrier in advanced experimental atherosclerosis and can be imaged and quantified ex vivo with the use of “no background” 19F MRI and MRS. This experimental strategy offers a potential new approach for quantification of endothelial dysfunction employing in vivo incubation with nanoparticle tracers.