Ferumoxytol is selectively taken up by atherosclerotic plaques and can thus be used for carotid USPIO-MRI. As USPIO and F-FDG uptake in atherosclerotic plaque do not correlate in this cohort, these agents may visualize different pathophysiological aspects of plaque inflammation.
The inflammatory profile of circulating monocytes is an important biomarker for atherosclerotic plaque vulnerability. Recent research revealed that peripheral lipid uptake by monocytes alters their phenotype toward an inflammatory state and this coincides with an increased lipid droplet (LD) content. Determination of lipid content of circulating monocytes is, however, not very well established. Based on Nile Red (NR) neutral LD imaging, using confocal microscopy and computational analysis, we developed NR Quantifier (NRQ), a novel quantification method to assess LD content in monocytes. Circulating monocytes were isolated from blood and used for the NR staining procedure. In monocytes stained with NR, we clearly distinguished, based on 3D imaging, phospholipids and exclusively intracellular neutral lipids. Next, we developed and validated NRQ, a semi-automated quantification program that detects alterations in lipid accumulation. NRQ was able to detect LD alterations after ex vivo exposure of isolated monocytes to freshly isolated LDL in a time- and dose-dependent fashion. Finally, we validated NRQ in patients with familial hypercholesterolemia and obese subjects in pre- and postprandial state. In conclusion, NRQ is a suitable tool to detect even small differences in neutral LD content in circulating monocytes using NR staining.
This article is available online at http://www.jlr.org Supplementary key words lipid droplets • methods • cholesterol and trafficking • fluorescence and confocal imagingAtherosclerosis is characterized by the recruitment of inflammatory cells into the intima, where excessive uptake of modified LDL particles, such as oxidized LDL, by monocytes and macrophages leads to foam cell formation (1), promoting the initiation of atherosclerotic lesions. Subsequent endothelial activation leads to continuous recruitment of circulating monocytes into the subintimal area, further increasing inflammatory activity of these lesions, leading to plaque progression and, eventually, plaque destabilization (2-4). Recently, it has been suggested that migration of circulating monocytes is not merely a reflection of local endothelial activation near atherogenic areas, but circulating monocytes may also display pro-adhesive properties in patients at increased cardiovascular risk (5). The factors leading to this systemic activation of circulating monocytes remain to be established. In dyslipidemic states, lipid accumulation is thought to contribute to the proadhesiveness of the circulating cells. In the postprandial state, lipids were found to be taken up by circulating monocytes, resulting in increased expression of the integrin CD11c, binding partner of vascular adhesion molecule-1 (VCAM-1) Abstract The inflammatory profile of circulating monocytes is an important biomarker for atherosclerotic plaque vulnerability. Recent research revealed that peripheral lipid uptake by monocytes alters their phenotype toward an inflammatory state and this coincides with an increased lipid droplet (LD) content. Determination of lipid content of circulating monocytes is, however, not very well established. Based on Nile Red (NR) neutral LD imaging, using confocal microscopy and computational analysis, we developed NR Quantifier (NRQ), a novel quantification method to assess LD content in monocytes. Circulating monocytes were isolated from blood and used for the NR staining procedure. In monocytes stained with NR, we clearly distinguished, based on 3D imaging, phospholipids and exclusively intracellular neutral lipids. Next, we developed and validated NRQ, a semi-automated quantification program that detects alterations in lipid accumulation. NRQ was able to detect LD alterations after ex vivo exposure of isolated monocytes to freshly isolated LDL in a time-and dose-dependent fashion. Finally, we validated NRQ in patients with familial hypercholesterolemia and obese subjects in pre-and postprandial state. In conclusion, NRQ is a suitable tool to detect even small differences in neutral LD content in circulating monocytes using NR staining.-Schnitzler, J. G., S. J. Bernelot Moens, F. Tiessens, G. J. Bakker, G. M. Dallinga-Thie, A. K. Groen, M. Nieuwdorp, E. S. G. Stroes, and J. Kroon. Nile Red Quantifier: a novel and quantitative tool to study lipid accumulation in patient-derived circulating monocytes using confocal microscopy J. Lipid Res.
Objectives The purpose of this study was to assess the feasibility of dual-energy CT-based material decomposition using dual-X-ray spectra information to determine local concentrations of holmium microspheres in phantoms and in an animal model. Materials and methods A spectral calibration phantom with a solution containing 10 mg/mL holmium and various tube settings was scanned using a third-generation dual-energy CT scanner to depict an energy-dependent and material-dependent enhancement vectors. A serial dilution of holmium (microspheres) was quantified by spectral material decomposition and compared with known holmium concentrations. Subsequently, the feasibility of the spectral material decomposition was demonstrated in situ in three euthanized rabbits with injected (radioactive) holmium microspheres. Results The measured CT values of the holmium solutions scale linearly to all measured concentrations and tube settings (R 2 = 1.00). Material decomposition based on CT acquisitions using the tube voltage combinations of 80/150 Sn kV or 100/150 Sn kV allow the most accurate quantifications for concentrations down to 0.125 mg/mL holmium. Conclusion Dual-energy CT facilitates image-based material decomposition to detect and quantify holmium microspheres in phantoms and rabbits. Key Points • Quantification of holmium concentrations based on dual-energy CT is obtained with good accuracy. • The optimal tube-voltage pairs for quantifying holmium were 80/150 Sn kV and 100/150 Sn kV using a third-generation dualsource CT system. • Quantification of accumulated holmium facilitates the assessment of local dosimetry for radiation therapies.
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