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
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