MRI of arthritis: Comparison of ultrasmall superparamagnetic iron oxide vs. Gd-DTPA

Purpose: To compare the ability of the ultrasmall superparamagnetic iron oxide (USPIO) SHU555C vs. gadopentetate dimeglumine (Gd-DTPA) to detect antigen-induced monoarthritis with MRI. Materials and Methods: Twelve seven-week-old female rats with an antigen-induced monoarthritis of the right knee were randomly assigned to two groups. Animals in group I (N= 6) underwent MRI using TI -weighted gradient-echo sequences before injection and at 2, 9, 17, 25, 33, 40, 47, 55, and 63 minutes postinjection (p.i.) of Gd-DTPA on day 1, and before injection and at 3, 23, 43, and 123 minutes p.i. of SHU555C on day 2. Animals in group 11 (N = 6) were imaged before injection and at 3. 23, 43, and 123 minutes p.i. using identical sequences. Signal-to-noise ratios (SNRs) and relative enhancement (Delta SI%) of arthritic and normal synovium were determined from region-of-interest (ROI) measurements in consensus reading by two experienced radiologists. Data were tested for significant differences between the two agents and between the arthritic and normal knees using a mixed-effect model and F-tests (P < 0.05). Joints were processed for histopathology as the gold standard. Results: USPIO and Gd-DTPA showed significant enhancement differences (P < 0.001). USPIO provided a progressive and persistent enhancement of arthritic joints while Gd-DTPA provided an early and rapidly declining enhancement. Maximal enhancement in synovitis was 400% at 40-120 minutes p.i. of USPIO vs. 300% at two minutes p.i. of Gd-DTPA. USPIO provided a significant higher difference in enhancement between the arthritic and normal synovium than Gd-DTPA (P < 0.001). Histopathology confirmed marked inflammatory synovial changes in all arthritis-induced right knee joints and normal synovium in all left knee joints. Conclusion: Both USPIO and Gd-DTPA detect arthritis by positive T1-enhancernent. Compared to standard GdDTPA, the USPIO SHU555C provides a comparable maximal T1-enhancement (at two minutes p.i for Gd-DTPA and between 43 and 123 minutes p.i. for SHU555C), but in addition it provides a prolonged TI-enhancement of synovitis and a higher difference between the relative enhancement of arthritic and normal synovium.