IntroductionRheumatoid arthritis (RA) is a chronic disease causing recurring inflammatory joint attacks. These attacks are characterized by macrophage infiltration contributing to joint destruction. Studies have shown that RA treatment efficacy is correlated to synovial macrophage number. The aim of this study was to experimentally validate the use of in vivo superparamagnetic iron oxide nanoparticle (SPION) labeled macrophages to evaluate RA treatment by MRI.MethodsThe evolution of macrophages was monitored with and without dexamethasone (Dexa) treatment in rats. Two doses of 3 and 1 mg/kg Dexa were administered two and five days following induction of antigen induced arthritis. SPIONs (7 mg Fe/rat) were injected intravenously and the knees were imaged in vivo on days 6, 10 and 13. The MR images were scored for three parameters: SPION signal intensity, SPION distribution pattern and synovial oedema. Using 3D semi-automated software, the MR SPION signal was quantified. The efficacy of SPIONs and gadolinium chelate (Gd), an MR contrast agent, in illustrating treatment effects were compared. Those results were confirmed through histological measurements of number and area of macrophages and nanoparticle clusters using CD68 immunostaining and Prussian blue staining respectively.ResultsResults show that the pattern and the intensity of SPION-labeled macrophages on MRI were altered by Dexa treatment. While the Dexa group had a uniform elliptical line surrounding an oedema pocket, the untreated group showed a diffused SPION distribution on day 6 post-induction. Dexa reduced the intensity of SPION signal 50-60% on days 10 and 13 compared to controls (P = 0.00008 and 0.002 respectively). Similar results were found when the signal was measured by the 3D tool. On day 13, the persisting low grade arthritis progression could not be demonstrated by Gd. Analysis of knee samples by Prussian blue and CD68 immunostaining confirmed in vivo SPION uptake by macrophages. Furthermore, CD68 immunostaining revealed that Dexa treatment significantly decreased the area and number of synovial macrophages. Prussian blue quantification corresponded to the macrophage measurements and both were in agreement with the MRI findings.ConclusionsWe have demonstrated the feasibility of MRI tracking of in vivo SPION-labeled macrophages to assess RA treatment effects.

The emerging importance of nanoparticle technology, including iron oxide nanoparticles for monitoring development, progression, and treatment of inflammatory diseases such as arthritis, drives development of imaging techniques. Studies require an imaging protocol that is sensitive and quantifiable for the detection of iron oxide over a wide range of concentrations. Conventional signal loss measurements of iron oxide nanoparticle containing tissues saturate at medium concentrations and show a nonlinear/nonproportional intensity to concentration profile due to the competing effects of T 1 and T 2 relaxation. A concentration calibration phantom and an in vivo study of intra-articular injection in a rat knee of known concentrations of iron oxide were assessed using the difference-ultrashort echo time sequence giving a positive, quantifiable, unambiguous iron signal and monotonic, increasing concentration response over a wide concentration range in the phantom with limited susceptibility artifacts and high contrast in vivo to all other tissues. This improved dynamic response to concentration opens possibilities for quantification due to its linear nature at physiologically relevant concentrations. Magn Reson Med 68:1544-1552, 2012. V C 2012 Wiley Periodicals, Inc.

The use of up to 50% ASIR in hip MDCT arthrography helps to reduce radiation dose by approximately 35-60%, while maintaining diagnostic image quality comparable to that of a regular-dose protocol using FBP.

Background Disease assessment using magnetic resonance imaging (MRI) in small animal models of rheumatoid arthritis (RA) is not a commonly used method to date. Inflammation and erosion histological scoring remain the gold standard and more recently μCT for bone erosion. Among the limitations of using histological scoring in longitudinal studies is the large number of animals needed making these studies not only time consuming but also labor intensive. Objectives The aim of this study was to validate the efficiency of MRI in assessing synovial and intra-articular oedema as well as bone erosion in affected knee joints over time in the presence and absence of anti-arthritic medication compared to other conventional methods. Methods Antigen induced Arthritis (AIA) was triggered in the right knee of 45 female Lewis rats using the following protocol; immunization twice by injecting 500 μg methylated bovine serum albumin (mBSA) emulsified in complete Freund’s adjuvant subcutaneously and 2*109 Bordetella Pertussis intraperitoneally on days -21 and -14. Mono-arthritis was induced on day 0 in the right knee: intra-articular 500μg BSA/50mL saline and left knee: 50μL saline. Animals were scanned using MRI and CT on the following days: 0, 3, 6, 10, 13, 17 and 5 animals were sacrificed at each time point. A Siemens 3T clinical scanner with 4cm loop coil was used for MRI with parameters: T2 2D-STIR for oedema, TR/TE 3700/20ms, resolution 0.156mm and 3D-GRE for bone erosion, TR/TE 14.3/5.9ms, resolution 0.31mm. Skyscan-1076 μCT was used with parameters: 65 kV anode voltage, 180mA, 0.45° rotation step, 316ms exposure time per view and final resolution of 35mm. Histology scoring of synovial infiltration and erosion were performed on H&E paraffin sections.Statistical analysis included double exponential fits of disease component score, derivative coefficients comparison (Friedman non-parametric) and time of maximum (tmax). Results On MRI, diseased joints showed rapid development of synovitis with periarticular oedema, followed by bone erosion. Fitting of scores shows consistency between animals, with good R2 also for individual animals (0.60 to 0.94). Wilcoxon analysis shows significant difference in tmax (p=0.043) for synovial and intra-articular oedema. Erosion continued to increase. A good correlation was seen between synovitis scores on MRI and histological sections, and between bone erosion scores on MRI and μCT images. Initial results indicate that MRI scores of inflammation and erosion performed on dexamethasone treated animals have the required sensitivity to detect differences due to treatment. Conclusions Noninvasive imaging techniques and specifically MRI provide a good and reliable method for long term assessment of AIA and anti-RA therapeutic trials and offer certain advantages over the conventional methods such as histological scoring. Disclosure of Interest None Declared