Novel quantitative digital image analysis methodology for assessment of inflammatory changes in MRI data in a post-hoc analysis of data acquired from a phase IIb study of baricitinib in patients with active rheumatoid arthritis.

PURPOSE: To evaluate a novel quantitative methodology to assess inflammatory changes in magnetic resonance imaging (MRI) data from patients with rheumatoid arthritis (RA) and the impact of image quality on imaging outcomes compared to the RA Magnetic Resonance Imaging Score (RAMRIS). METHODS: Three-dimensional, T1-weighted, fat-suppressed MRI sequences of the hand/wrist before and after intravenous Gadolinium contrast from patients with RA in a placebo-controlled clinical trial (NCT01185353) were re-evaluated post hoc. The methodology was integrated into proprietary software (DYNAMIKA®) and assessed inflammation through pixelated measurements of the contrast-enhancing (inflammatory) volume. A semi-automatic approach outlined contrast-enhancing synovial tissue in the wrist and second to fifth metacarpophalangeal joints with a rough region of interest (ROI); quantitative imaging biomarkers were generated by means of quantitative total volume of inflammation and quantitative degree of inflammation relative to the signal in a 1 cm in diameter ROI in the center of the thenar or lumbrical muscle for internal reference. The time from Gadolinium injection to finalization of the post-contrast images was calculated from the images' Digital Imaging and Communications in Medicine header. An experienced reader graded image quality as poor, acceptable, or good. RESULTS: Results from this quantitative methodology, especially when excluding images with poor quality scores (14-32%), provided a more pronounced and monotonically increasing dose-response than the original RAMRIS results on synovitis and osteitis. CONCLUSIONS: This computer-aided quantitative scoring method provided continuous measures of inflammatory changes relative to muscle and may be more sensitive and interpretable concerning dose/response separation between RA treatment groups.

Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology.

OBJECTIVE: To determine whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) evaluated using semi-automatic image processing software can accurately assess synovial inflammation in rheumatoid arthritis (RA) knee joints. METHODS: In 17 RA patients undergoing knee surgery, the average grade of histological synovial inflammation was determined from four biopsies obtained during surgery. A preoperative series of T(1)-weighted dynamic fast low-angle shot (FLASH) MR images was obtained. Parameters characterizing contrast uptake dynamics, including the initial rate of enhancement (IRE), were generated by the software in three different areas: (I) the entire slice (Whole slice); (II) a manually outlined region of interest (ROI) drawn quickly around the joint, omitting large artefacts such as blood vessels (Quick ROI); and (III) a manually outlined ROI following the synovial capsule of the knee joint (Precise ROI). Intra- and inter-reader agreement was assessed using the intra-class correlation coefficient (ICC). RESULTS: The IRE from the Quick ROI and the Precise ROI revealed high correlations to the grade of histological inflammation (Spearman's correlation coefficient (rho) = 0.70, p = 0.001 and rho = 0.74, p = 0.001, respectively). Intra- and inter-reader ICCs were very high (0.93-1.00). No Whole slice parameters were correlated to histology. CONCLUSION: DCE-MRI provides fast and accurate assessment of synovial inflammation in RA patients. Manual outlining of the joint to omit large artefacts is necessary.