Quantitative dual-energy CT material decomposition of holmium microspheres: local concentration determination evaluated in phantoms and a rabbit tumor model.

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 (R2 = 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 dual-source CT system. • Quantification of accumulated holmium facilitates the assessment of local dosimetry for radiation therapies.

Nile Red Quantifier: a novel and quantitative tool to study lipid accumulation in patient-derived circulating monocytes using confocal microscopy.

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.

Evaluation of ultrasmall superparamagnetic iron-oxide (USPIO) enhanced MRI with ferumoxytol to quantify arterial wall inflammation.

BACKGROUND AND AIMS: Inflammation in atherosclerotic plaques is an important determinant of plaque vulnerability, and can be detected non-invasively using ultra-small superparamagnetic iron-oxide (USPIO) enhanced MRI. The aims of the current study were: 1) to determine whether ferumoxytol can be used for USPIO-MRI of atherosclerotic plaques, 2) to establish a protocol for quantitative USPIO-MRI of carotid artery plaques using ferumoxytol, and 3) to study the relation between USPIO uptake and plaque burden and 18F-fluorodeoxyglucose (FDG) uptake (measured by 18F-FDG PET/CT scan) in atherosclerotic plaques. METHODS: In 9 patients with carotid artery stenosis >30% and 4 healthy controls, quantitative R2* MRI scans of the carotid arteries were performed before and 72 h after USPIO administration (4 mg/kg ferumoxytol). USPIO uptake was assessed by quantifying the difference in R2* (ΔR2*) between baseline and post-USPIO scans. In addition to MRI, 18F-FDG PET/CT was performed on both carotid arteries. MR and PET/CT images were co-registered, and 18F-FDG uptake was quantified in all slices containing atherosclerotic plaque. RESULTS: Infusion of ferumoxytol resulted in higher R2* values after 72 h in atherosclerotic plaques (ΔR2* 24.6 ± 19.8 s-1; p = 0.0003), but not in the healthy control vessel wall (ΔR2* 2.6 ± 5.6 s-1, p = 0.23). USPIO uptake in patients was higher in atherosclerotic plaques compared to the patient non-plaque vessel wall (ΔR2* of 24.6 ± 19.8 vs. 7.5 ± 9.3 s-1, p = 0.004). No correlation was found between USPIO uptake and 18F-FDG uptake in atherosclerotic plaques (R2 = 0.03, p = 0.55). CONCLUSIONS: Ferumoxytol is selectively taken up by atherosclerotic plaques and can thus be used for carotid USPIO-MRI. As USPIO and 18F-FDG uptake in atherosclerotic plaque do not correlate in this cohort, these agents may visualize different pathophysiological aspects of plaque inflammation.