Rheumatoid Arthritis MRI Scoring System Research Articles

Predictive Value of Magnetic Resonance Imaging-detected Tenosynovitis of the Metacarpophalangeal and Wrist Joints for the Development of Rheumatoid Arthritis among Patients with Undifferentiated Arthritis.

Objective The early diagnosis of rheumatoid arthritis (RA) improves disease outcomes. Using bilateral magnetic resonance imaging (MRI), we investigated whether or not tenosynovitis at the level of the metacarpophalangeal (MCP) and wrist joints, as well as non-symmetrical versus symmetrical involvement, predicts RA development in undifferentiated arthritis (UA) patients. Methods We collected the clinical and serological findings as well as bilateral gadolinium-enhanced 1.5-T MRI data of UA patients after 1 year. A multivariate logistic regression analysis was used to determine the association of tenosynovitis in UA with RA development. Patients and Materials Ninety-one UA patients from the Nagasaki Early Arthritis Clinic who did not meet the 2010 European League Against Rheumatism/American College of Rheumatology classification criteria for RA were selected. Tenosynovitis at the MCP and wrist joints was scored according to the RA MRI scoring system. Results Of these 91 UA patients, 29 (31.9%) progressed to RA, with a median disease duration of 3 months, despite only 10.9% being positive for anti-cyclic citrullinated peptide antibody (ACPA). A univariate analysis showed higher MCP tenosynovitis scores, MCP flexor tenosynovitis, and symmetrical MCP tenosynovitis in the RA development group than in the non-development group (p <0.05). A multivariate analysis showed that symmetrical MCP tenosynovitis was independently associated with RA development after adjusting for age, gender, swollen joint count, C-reactive protein level, and ACPA positivity (odds ratio: 4.96). The presence of symmetrical MCP tenosynovitis had low sensitivity (35%) but high specificity (87%) for RA development. Conclusion MRI-detected tenosynovitis, especially symmetrical findings at the MCP joint, is predictive of RA development in a UA population with low ACPA positivity.

Interosseous tendon inflammation in the hands of patients with clinically suspect arthralgia: analysis of MRI data from a prospective cohort study.

Inflammation around the tendons of interosseous muscles of the hand (interosseous tendon inflammation) was recently observed with MRI for the first time in patients with rheumatoid arthritis and in at-risk individuals with detectable anti-citrullinated protein antibodies, generating the hypothesis that interosseous tendon inflammation precedes clinical arthritis. To better understand the role of interosseous tendon inflammation during the development of rheumatoid arthritis, we studied the frequency of interosseous tendon inflammation in healthy individuals and in those with arthralgia that was suspected of progressing to rheumatoid arthritis (ie, clinically suspect arthralgia) and the association of interosseous tendon inflammation with other symptoms of inflamed joint tissues and with clinical arthritis development. Adult (age ≥18 years) patients who presented with clinically suspect arthralgia and symptom-free (control) individuals underwent contrast-enhanced hand MRI. MRIs were evaluated for interosseous tendon inflammation on the radial and ulnar sides of the second to fifth metacarpophalangeal joints, and for synovitis, tenosynovitis, and osteitis using the rheumatoid arthritis MRI scoring system. Patients with clinically suspect arthralgia were followed up for clinical arthritis development. The presence of local tenosynovium was examined using immunohistochemistry for anti-CD55 and anti-CD68 on tissue from the hands of three embalmed bodies donated for scientific research. The primary outcome for the cross-sectional part of the study was the presence of interosseous tendon inflammation on MRI. The primary outcome for the longitudinal part of the study was development of clinical arthritis. Between April 3, 2012, and May 20, 2020, 667 patients with clinically suspect arthralgia (mean age 44 years [SD 13], 504 [76%] were women and 163 [24%] were men) underwent contrast-enhanced hand MRI. Between Nov 1, 2013, and Nov 30, 2014, 193 symptom-free controls were recruited (mean age 50 years [SD 16], 136 [70%] were women and 57 [30%] were men). Two (1%) of 193 symptom-free controls had interosseous tendon inflammation. Immunohistochemistry of cadaveric hand tissues showed no tenosynovium surrounding interosseous tendons. At inclusion, 67 (10%) of 667 patients with clinically suspect arthralgia had interosseous tendon inflammation (p<0·0001 vs symptom-free controls). Interosseous tendon inflammation occurred more frequently if synovitis (odds ratio [OR] 2·2 [95% CI 1·2-4·2]), or tenosynovitis (OR 9·7 [5·5-17·0]), was present at metacarpophalangeal joints. A three-dimensional MRI reconstruction suggested confluency of interosseous tendon inflammation with metacarpophalangeal-flexor-tenosynovitis. 91 (16%) of 558 patients with clinically suspect arthralgia developed clinical arthritis during follow-up (median total follow-up 25·3 months [95% CI 25·1-25·5]). Patients with clinically suspect arthralgia with interosseous tendon inflammation had a higher risk of developing clinical arthritis (hazard ratio [HR] 4·5 [2·8-7·2]), which was attenuated but still significant after adjusting for concomitant synovitis, tenosynovitis, or osteitis (HR 1·7 [1·02-2·8]). Interosseous tendon inflammation is almost absent in symptom-free individuals but occurs in people with clinically suspect arthralgia, in whom it correlates with symptoms and is associated with the development of clinical arthritis. The absence of local tenosynovium suggests that interosseous tendon inflammation arises from expanding local subclinical inflammation in the pre-arthritis phase of rheumatoid arthritis. European Research Council and the Dutch Arthritis Society.

Comparison between 2D FSE T2-weighted Dixon MRI and contrast-enhanced 2D FSE and 3D FSPGR T1-weighted Dixon MRI to quantify inflammation in hands of patients with early rheumatoid arthritis

PurposeThe purpose of this study was to compare two-dimensional (2D) T2-weighted, contrast-enhanced 2D T1-weighted and contrast-enhanced three-dimensional (3D) T1-weighted Dixon MRI sequences to assess disease activity using the RAMRIS scoring system in hands of patients with early rheumatoid arthritis. Materials and methodsTwenty-five patients (19 women, 6 men; mean age 51.4 years ± 12.7 years [SD], age range: 28–70 years) with rheumatoid arthritis prospectively underwent MRI examination of both hands at 1.5 T using 2D fast spin-echo (FSE) T2-weighted, contrast-enhanced 2D FSE T1-weighted and contrast-enhanced 3D fast spoiled gradient echo (FSPGR) T1-weighted Dixon sequences. Three radiologists independently assessed disease activity according to RAMRIS using Dixon water-only and fat-only images. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique and interobserver agreements. ResultsAgreement to assess total RAMRIS score was very good between the MRI protocols (mean ICC ranging from 0.81 to 0.93) and between readers (mean ICC ranging from 0.91 to 0.94). Mean total RAMRIS scores of the three readers were significantly greater with contrast-enhanced 3D FSPGR T1-weighted (42.73 ± 29.39) than with contrast-enhanced 2D FSE T1-weighted (35.81 ± 25.48) and 2D FSE T2-weighted (32.20 ± 25.06) Dixon sequences. Conclusion2D FSE T2-weighted, contrast-enhanced 2D FSE T1-weighted Dixon and contrast-enhanced 3D FSPGR T1-weighted Dixon protocols are reproducible alternatives for the RAMRIS scoring in hands of patients with early rheumatoid arthritis. Coupling contrast-enhanced 3D FSPGR T1-weighted and 2D FSE T2-weighted sequences might be the most efficient option to completely assess the rheumatoid arthritis -related synovial and bone changes with the Dixon method.

Intermetatarsal Bursitis, a Novel Feature of Juxtaarticular Inflammation in Early Rheumatoid Arthritis Related to Clinical Signs: Results of a Longitudinal Magnetic Resonance Imaging Study.

Intermetatarsal bursae in the forefeet possess a synovial lining similar to joints and tendon sheaths. Inflammation of these bursae (intermetatarsal bursitis [IMB]) was recently identified as specific for early rheumatoid arthritis (RA). The present study was undertaken to determine if IMB is indeed an RA feature by assessing the following: 1) the association with other local inflammatory measures (synovitis, tenosynovitis, and osteitis), 2) the association with clinical signs, and 3) whether it responds to disease-modifying antirheumatic drug (DMARD) therapy similarly to other local inflammatory measures. One hundred fifty-seven consecutive early RA patients underwent unilateral contrast-enhanced 1.5T forefoot magnetic resonance imaging (MRI) at diagnosis. MRIs were evaluated for IMB presence and for synovitis, tenosynovitis, and osteitis in line with the RA MRI Scoring (RAMRIS) system (summed as RAMRIS inflammation). MRIs at 4, 12, and 24 months were evaluated for IMB presence and size in patients who had IMB at baseline and received early DMARD therapy. Logistic regression and generalized estimating equations were used. Anti-citrullinated protein antibody (ACPA) stratification was performed. Sixty-nine percent of RA patients had ≥1 IMB. In multivariable analysis on bursa level, presence of IMB was independently associated with local presence of synovitis and tenosynovitis, with odds ratios (OR) of 1.69 (95% confidence interval [95% CI] 1.12, 2.57) and 2.83 (95% CI 1.80, 4.44), respectively, but not osteitis. On the patient level, IMB presence was most strongly associated with tenosynovitis (OR 2.92 [95% CI 1.62, 5.24]). IMB presence was associated with local joint swelling (OR 2.7 [95% CI 1.3, 5.3]) and tenderness (OR 1.7 [95% CI 1.04, 2.9]) independent of RAMRIS inflammation. During treatment, IMB size decreased between 0 and 12 months. This decrease associated with decrease in RAMRIS inflammation, which was driven by synovitis decrease. Within ACPA-positive and ACPA-negative RA, similar results were obtained. IMB particularly accompanies inflammation of the synovial lining of joints and tendon sheaths, showed a similar treatment response after DMARD initiation, and associates with typical clinical signs. These findings suggest that IMB represents a frequently present novel RA feature of juxtaarticular synovial inflammation.

Bone erosions by MRI in first-degree relatives of patients with RA: an exploratory study.

First-degree relatives (FDR) of patients with rheumatoid arthritis (RA) are at increased risk of RA diagnosis. Magnetic resonance imaging (MRI) has been proposed as a useful tool to detect subclinical synovitis and bone abnormalities as predictors of progression to RA. The presence of grade ≥ 2 bone erosions in RA MRI scoring system (RAMRIS) was reported to be RA-specific. We aim to describe the prevalence and characteristics of MRI findings in RA patients and FDR. A cross-sectional and exploratory study of 60 individuals was performed in 38 RA patients and 22 FDR with hand arthralgia without clinical arthritis and positive rheumatoid factor or anticitrullinated protein antibodies. All patients underwent an MRI and were evaluated for synovitis, bone erosion, and bone marrow edema. We evaluated second to fifth metacarpophalangeal joints of the dominant hand according to RAMRIS. Among the total population, eighteen (30%) subjects had grade ≥ 2 bone erosions, and 42 (70%) had at least one erosion of any grade. In patients with grade ≥ 2 bone erosions, 12 (31.6%) were from RA patients and 6 (27.2%) from FDR (p = 0.72). In patients with erosions of any grade, 26 (68.4%) were from RA patients and 15 (68.2%) were from FDR (p = 0.98). A high prevalence of bone erosions was found in RA patients' FDR who had symptoms without clinical arthritis and positive serology. MRI might be helpful in this population for an early detection of RA-specific erosions. The prognosis and the treatment decisions in these subjects should be elucidated. • First-degree relatives (FDR) of rheumatoid arthritis (RA) patients with positive serology and joint symptoms constitute a select subpopulation of individuals with an increased risk of developing RA. • Magnetic resonance imaging (MRI) of FDR shows a high prevalence of bone erosions of any grade, grade ≥ 2 erosions, and synovitis. • MRI might be helpful in FDR of RA patients to screen for the presence of RA-specific erosions or clinically undetectable synovitis.

During development of rheumatoid arthritis, intermetatarsal bursitis may occur before clinical joint swelling: a large imaging study in patients with clinically suspect arthralgia.

ObjectivesIntermetatarsal bursitis (IMB) represents juxta-articular synovial inflammation of the intermetatarsal bursae. Recent MRI studies identified IMB as feature of early RA, but whether IMB already occurs in the pre-arthritic phase is unknown. We performed a large MRI study in clinically suspect arthralgia (CSA) to assess the occurrence and prognostic value of IMB.MethodsA total of 577 consecutive CSA patients underwent contrast-enhanced MRI of the forefoot, metacarpophalangeal joints and wrist. MRIs were evaluated for subclinical synovitis/tenosynovitis/osteitis in line with the RA MRI scoring system (summed as RAMRIS inflammation) and for IMB. IMB was considered present if uncommon in the general population at the same location (i.e. size scored above the 95th percentile in age-matched symptom-free controls). The relation of IMB with other MRI-detected subclinical inflammation (synovitis/tenosynovitis/osteitis) was studied. Cox-regression assessed the association with clinical arthritis development during median 25 months follow-up. ACPA stratification was performed.ResultsAt presentation with CSA, 23% had IMB. IMB was more frequent in ACPA-positive than ACPA-negative CSA (47% vs 19%, P < 0.001). Patients with IMB were more likely to also have subclinical synovitis [OR 3.4 (95% CI 1.8, 6.5)] and tenosynovitis [5.9(2.8, 12.6)]. IMB conferred higher risk of developing arthritis [HR 1.6(1.0–2.7) adjusted for other subclinical inflammation]. IMB-presence predicted arthritis development in ACPA-positive CSA [adjusted HR 2.2(1.0–4.7)], but not in ACPA-negative CSA-patients [0.8(0.4–1.7)].ConclusionApproximately a quarter of CSA patients have IMB, which is frequently accompanied by subclinical synovitis and tenosynovitis. IMB precedes development of clinical arthritis, particularly in ACPA-positive CSA. These results reinforce the notion that juxta-articular synovial inflammation is involved in the earliest phases of RA development.

Distribution of bony erosions in feet and performance of two bone erosion scores: A dual-energy computed tomography study of 61 patients with gout.

ObjectivesTo assess the distribution of bone erosions and two erosion scores in the feet of patients with gout and analyze the association between erosion scores and monosodium urate (MSU) crystal deposition using dual-energy computed tomography (DECT).Materials and methodsWe included all patients who underwent DECT of both feet between 2016 and 2019 in our radiology department, with positive detection of MSU deposits. Data on sex, age, treatment, serum urate, and DECT urate volumes were obtained. CT images were analyzed to score bone erosions in 31 sites per foot by using the semi-quantitative method based on the Rheumatoid Arthritis MRI Scoring (RAMRIS) system and the Dalbeth-simplified score. Reproducibility for the two scores was calculated with intraclass correlation coefficients (ICCs). Correlations between clinical features, erosion scores and urate crystal volume were analyzed by the Spearman correlation coefficient (r).ResultsWe studied 61 patients (mean age 62.0 years); 3,751 bones were scored. The first metatarsophalangeal joint and the midfoot were the most involved in terms of frequency and severity of bone erosions. The distribution of bone erosions was not asymmetrical. The intra- and inter-observer reproducibility was similar for the RAMRIS and Dalbeth-simplified scores (ICC 0.93 vs 0.94 and 0.96 vs 0.90). DECT urate volume was significantly correlated with each of the two erosion scores (r = 0.58–0.63, p < 0.001). There was a high correlation between the two scores (r = 0.96, p < 0.001).ConclusionsDECT demonstrates that foot erosions are not asymmetric in distribution and predominate at the first ray and midfoot. The two erosion scores are significantly correlated with DECT urate volume. An almost perfect correlation between the RAMRIS and Dalbeth-simplified scores is observed.

Contrast-enhanced T1-weighted Dixon water- and fat-only images to assess osteitis and erosions according to RAMRIS in hands of patients with early rheumatoid arthritis

PurposeTo assess the agreement between readers using contrast-enhanced T1-weighted Dixon water- and fat-only images and OMERACT-recommended sequences for the scoring of osteitis and erosions according to the rheumatoid arthritis (RA) MRI scoring system (RAMRIS) in hands of patients with early RA. Materials and methodsBoth hands of 24 patients (16 women, 8 men; mean age, 45.7±14.5 [SD] years; age range: 25–70 years) with early RA were prospectively imaged with fat-saturated T2-weighted sequences, non-Dixon T1-weighted imaging prior to contrast material injection and T1-weighted Dixon imaging after contrast material injection at 1.5T. There were Two radiologists separately quantified osteitis and erosions according to RAMRIS using contrast-enhanced T1-weighted Dixon water-only and fat-saturated T2-weighted images for osteitis and contrast-enhanced T1-weighted Dixon fat-only and T1-weighted images prior to contrast material injection for erosions. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique, intra-observer and inter-observer agreement. ResultsMean ICC for the agreement between Dixon and non-Dixon images ranged from 0.68 (95%CI: 0.20–0.90) to 0.99 (95%CI: 0.95–1.00) for the scoring of osteitis and from 0.77 (95%CI: 0.38–0.93) to 0.99 (95%CI: 0.95–1.00) for the scoring of erosions. Mean ICC for the agreement between first and second readings ranged from 0.94 (95%CI: 0.81–0.98) to 0.97 (95%CI: 0.91–0.99) for the scoring of osteitis using Dixon and 0.91 (95%CI: 0.72–0.97) to 0.98 (95%CI: 0.92–0.99) using non-Dixon images and from 0.80 (95%CI: 0.45–0.94) to 0.97 (95%CI: 0.91–0.99) for the scoring of erosions using Dixon and 0.72 (95%CI: 0.29–0.91) to 0.98 (95%CI: 0.92–0.99) using non-Dixon images. ConclusionContrast-enhanced T1-weighted Dixon water- and fat-only images can serve as an alternative to fat-saturated T2-weighted and T1-weighted MRI sequences for the assessment of osteitis and erosions according to the RAMRIS scoring system in hands of patients with early RA.

MRI of the joint and evaluation of the granulocyte-macrophage colony-stimulating factor-CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study.

Otilimab is a human monoclonal antibody that inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF), a driver in many immune-mediated inflammatory conditions. We evaluated the effect of otilimab on the GM-CSF-chemokine (C-C motif) ligand 17 (CCL17) axis and synovitis in patients with rheumatoid arthritis. This phase 2a, randomised, double-blind, multicentre, placebo-controlled, parallel-group study was done at nine sites across the USA, Poland, and Germany. Patients aged 18 years or older with rheumatoid arthritis per American College of Rheumatology-European League Against Rheumatism 2010 criteria and receiving stable methotrexate were randomly assigned (3:1) by an interactive response technology system to either subcutaneous otilimab 180 mg or placebo once weekly for 5 weeks, then every other week until week 10 (within a 12-week treatment period), followed by a 10-week safety follow-up. Randomisation was stratified by early rheumatoid arthritis (≤2 years since diagnosis) and established rheumatoid arthritis (>2 years since diagnosis). Patients and study personnel (except for an unblinded coordinator or nurse who prepared and administered the study drug) were blinded to treatment assignment; the syringe was shielded during administration. Patients were enrolled by study investigators and allocated to a treatment by central randomisation on the basis of a schedule generated by the sponsor. The primary endpoint was change over time (assessed at baseline and weeks 1, 2, 4, 6, 8, 12, and 22 of follow-up) in 112 biomarkers, including target engagement biomarkers and those that may be indicative of rheumatoid arthritis disease activity and response to otilimab. Secondary endpoints were change from baseline in synovitis, osteitis and erosion assessed by rheumatoid arthritis MRI scoring system (RAMRIS) and rheumatoid arthritis MRI quantitative score (RAMRIQ), and safety evaluation. The primary, secondary, and safety endpoints were assessed in the intention-to-treat population. Biomarker and MRI endpoints were analysed for differences between treatment groups using a repeated measures model. This study is registered with ClinicalTrials.gov, NCT02799472. Between Aug 9, 2016, and Oct 30, 2017, 39 patients were randomly assigned and included in the analysis (otilimab n=28; placebo n=11). In the otilimab group, mean serum concentrations of GM-CSF-otilimab complex peaked at week 4 (138·4 ng/L, 95% CI 90·0-212·9) but decreased from week 6-12. CCL17 concentrations decreased from baseline to week 1, remained stable to week 8, and returned to baseline at week 12; least-squares mean ratio to baseline was 0·65 (95% CI 0·49-0·86; coefficient of variation 13·60) at week 2, 0·68 (0·53-0·88; 12·51) at week 4, 0·78 (0·60-1·00; 12·48) at week 6, and 0·68 (0·54-0·85; 11·21) at week 8. No meaningful change in CCL17 concentrations was observed with placebo. In the otilimab group, the least-squares mean ratio to baseline in MMP-degraded type I collagen was 0·86-0·91 over weeks 1-8, returning to baseline at week 12; concentrations remained above baseline at all timepoints in the placebo group. There were no observable differences between otilimab and placebo for all other biomarkers. At week 12, least-squares mean change in RAMRIS synovitis score from baseline was -1·3 (standard error [SE] 0·6) in the otilimab group and 0·8 (1·2) with placebo; RAMRIQ synovitis score showed a least-squares mean change from baseline of -1417·0 μl (671·5) in the otilimab group and -912·3 μl (1405·8) with placebo. Compared with placebo, otilimab did not show significant reductions from baseline to week 12 in RAMRIS synovitis, osteitis and bone erosion, or in RAMRIQ synovitis and erosion damage. Adverse events were reported in 11 (39%) of 28 otilimab-treated and four (36%) of 11 placebo-treated patients, most commonly cough in the otilimab group (2 [7%] of 28; not reported in placebo group), and pain in extremity (four [36%] of 11) and rheumatoid arthritis (two [18%] of 11) in the placebo group (not reported in otilimab group). There were no serious adverse events or deaths. Serum concentrations of GM-CSF-otilimab complex indicated that target engagement was achieved with initial weekly dosing, but not sustained with every other week dosing. CCL17 might be a pharmacodynamic biomarker for otilimab activity in future studies. Otilimab was well tolerated and, despite suboptimal exposure, showed some evidence for improved synovitis over 12 weeks in patients with active rheumatoid arthritis. GlaxoSmithKline.

Efficacy and safety of low-dose glucocorticoids combined with methotrexate and hydroxychloroquine in the treatment of early rheumatoid arthritis

Introduction:Glucocorticoids (GCs), especially low-dose GCs, are commonly prescribed for rheumatoid arthritis (RA), although the risk/benefit ratio is controversial. A randomized, double-blind clinical trial was performed to evaluate the efficacy and safety of low-dose oral GCs combined with methotrexate (MTX) and hydroxychloroquine (HCQ) in early RA (ERA).Methods:Eighty untreated ERA patients were randomized into the trial (GCs + MTX + HCQ) and control (placebo + MTX + HCQ) groups, for 1-year treatment. Therapeutic evaluation indices were American College of Rheumatology (ACR) 20 of ACR, disease activity score (DAS) 28- erythrocyte sedimentation rate (ESR), visual analog scale scores, joint function, health assessment questionnaire-disability index score, morning stiffness duration, C-reaction protein and ESR. The clinical indicators were evaluated pre-treatment and at 1st, 3th, 6th and 12th month of treatment. The MRI data of single joint (ie, the most swollen joint) for each patient were acquired with a revised OMERACT RAMRIS Scoring System before and after treatment. The correlation analysis was adopted to confirm whether the efficacy of GC treatment is related to the time of RA onset. The side effects (eg, gastrointestinal reactions, liver dysfunction, upper respiratory tract infection, leukocyte reduction) were also monitored.Results:At 1st month, 55% and 20% cases in the experimental and control groups achieved ACR20 response, respectively, indicating a significant difference (χ2 = 16.157, P < .001). This trend continued until 6th month. At 12th month, the number of patients achieved ACR20 response was similar in both groups. At 1st to 6th month, DAS28- ESR scores in the experimental group were significantly lower than control values (all p < .05). The experimental group showed improved inflammation, quality of life and radiological symptoms. Bone erosion remained unchanged in the experimental group, while worsening in control group. Correlation coefficients between RA duration and DAS28-ESR score were 0.496, 0.464, 0.509, and 0.550 at 1st, 3th, 6th, and 12th month, respectively. No differences were found in adverse events between the 2 groups.Conclusions:Low-dose GCs combined with MTX and HCQ significantly achieves disease remission indexed by ACR20 and DAS28-ESR, and improves clinical and radiological outcomes in ERA patients at the early stage, with superiority over placebo + MTX + HCQ, without enhancing adverse reactions.

Whole-body Magnetic Resonance Imaging in Psoriatic Arthritis, Rheumatoid Arthritis, and Healthy Controls: Interscan, Intrareader, and Interreader Agreement and Distribution of Lesions.

Whole-body MRI (WBMRI) is a promising technique for monitoring patients' global disease activity in inflammatory joint diseases. The validation of WBMRI is limited; no studies have evaluated the test-retest agreement (interscan agreement) and only a few have assessed the intra- and interreader agreement. Therefore, we first examined the interscan agreement of WBMRI in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and healthy controls (HC); and second, we evaluated the intra- and interreader agreement and agreement with conventional hand MRI and determined the distribution of lesions. WBMRI was performed twice at a 1-week interval in 14 patients with PsA, 10 with RA, and 16 HC. Images were anonymized and read in pairs with unknown chronological order by experienced readers according to the Outcome Measures in Rheumatology (OMERACT) WBMRI, Canada-Denmark MRI, and the RA MRI scoring system (RAMRIS) and the PsA MRI scoring system (PsAMRIS). Ten image sets were reanonymized for assessment of intra- and interreader agreement. Agreement was calculated on lesion level by percentage exact agreement (PEA) and Cohen κ, and for sum scores by absolute agreement, single-measure intraclass correlation coefficient (ICC). WBMRI of the spine and peripheral joints and entheses generally showed moderate to almost perfect interscan agreement with PEA ranging from 95% to 100%, κ 0.71-1.00, and ICC 0.95 to 1.00. Intra- and interreader data generally showed moderate to almost perfect agreement. Agreement with conventional MRI varied. More lesions were found in patients than in HC. WBMRI showed good interscan agreement, implying that repositioning of the patient between examinations does not markedly affect scoring of lesions. Intra- and interreader agreement were moderate to almost perfect.

Do magnetic resonance imaging-detected erosions predict progression to rheumatoid arthritis in patients presenting with clinically suspect arthralgia? A longitudinal study

Objective: Radiographic joint erosions are a hallmark of rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is more sensitive than radiographs in detecting erosions. It is unknown whether MRI-detected erosions are predictive for RA development in patients with clinically suspect arthralgia (CSA). Therefore, we investigated the prognostic value of MRI-detected erosions, defined as any MRI erosion, or MRI erosion characteristics that were recently identified as specific for RA in patients with evident arthritis. Method: Patients presenting with CSA (n = 490) underwent contrast-enhanced 1.5 T MRI of the wrist, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints. MRIs were scored according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system (RAMRIS). Presence of any MRI erosion (present in < 5% of symptom-free controls) and RA-specific erosion characteristics as identified previously (grade ≥ 2 erosions, erosions in MTP5, erosions in MTP1 if aged < 40 years) were studied with clinically apparent inflammatory arthritis development as outcome. Analyses were corrected for age and MRI-detected subclinical inflammation. Results: Erosions were present in 20%. Presence of any MRI erosion was not associated with arthritis development [multivariable analysis hazard ratio (HR) 0.97 (95% confidence interval 0.59–1.59)]. The different RA-specific erosion characteristics were not predictive [grade ≥ 2 HR 1.05 (0.33–3.34), erosions in MTP5 HR 1.08 (0.47–2.48), and MTP1 if aged < 40 years HR 1.11 (0.26–4.70)]. Erosion scores were higher in anti-citrullinated protein antibody (ACPA)-positive than in ACPA-negative patients (median 2.0 vs 1.0, p = 0.002), and related to more subclinical inflammation. Within both subgroups, MRI erosions were not predictive. Conclusions: MRI-detected erosions in hands and feet were not predictive for inflammatory arthritis development. Therefore, evaluating MRI for erosions in addition to subclinical inflammation does not provide added clinical value in CSA.

Conventional versus ultrasound treat to target: no difference in magnetic resonance imaging inflammation or joint damage over 2 years in early rheumatoid arthritis.

To investigate whether an ultrasound-guided treat-to-target strategy for early RA would lead to reduced MRI inflammation or less structural damage progression compared with a conventional treat-to-target strategy. A total of 230 DMARD-naïve early RA patients were randomized to an ultrasound tight control strategy targeting DAS <1.6, no swollen joints and no power Doppler signal in any joint or a conventional strategy targeting DAS <1.6 and no swollen joints. Patients in both arms were treated according to the same DMARD escalation strategy. MRI of the dominant hand was performed at six time points over 2 years and scored according to the OMERACT RA MRI scoring system. A total of 218 patients had baseline and one or more follow-up MRIs and were included in the analysis. The mean MRI score change from baseline to each follow-up and the 2 year risk for erosive progression were compared between arms. MRI bone marrow oedema, synovitis and tenosynovitis improved over the first year and was sustained during the second year of follow-up, with no statistically significant differences between the ultrasound and the conventional arms at any time point. The 2 year risk for progression of MRI erosions was similar in both treatment arms: ultrasound arm 39%, conventional arm 33% [relative risk 1.16 (95% CI 0.81, 1.66), P = 0.40]. Incorporating ultrasound information in treatment decisions did not lead to reduced MRI inflammation or less structural damage compared with a conventional treatment strategy. The findings support that systematic use of ultrasound does not provide a benefit in the follow-up of patients with early RA. Clinicaltrials.gov, http://clinicaltrials.gov, NCT01205854.

Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis

BackgroundThe objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA).MethodsThis was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression.ResultsData from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p < 0.01); changes in RAMRIQ synovitis and osteitis at months 1 and 3 were significant predictors of RAMRIS erosions and radiographic progression at month 12 (all p < 0.01). In subsequent multivariate analyses, RAMRIS erosion change at month 1 (p < 0.05) and RAMRIQ osteitis changes at months 1 and 3 (both p < 0.01) were significant independent predictors of radiographic progression at month 12. Univariate analyses demonstrated that changes in Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at months 1 and 3 were not predictive of month 12 radiographic progression.ConclusionsMRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures.Trial registrationClinicalTrials.gov, NCT01164579.

Fully automated segmentation of wrist bones on T2-weighted fat-suppressed MR images in early rheumatoid arthritis.

Magnetic resonance imaging (MRI) allows accurate determination of soft tissue and bone inflammation in rheumatoid arthritis. Inflammation can be measured semi-quantitatively using the well-established RA-MRI scoring system (RAMRIS), but its application is time consuming in routine clinical practice. To fully realize an automated quantitation of inflammation scoring for clinical use, automatic segmentation of the wrist bones on MR imaging is needed. Most previous studies extracted the wrist bones on T1-weighted (T1W) MR images, and then used registration to segment T2W fat-suppressed images for bone marrow oedema quantification, introducing spatial errors into the process. Relatively little work has tried segmentation directly from T2W fat-suppressed images and no prior study have used convolution neural network (CNN) to segment the wrist bones. The purpose of this study is to develop a CNN-based algorithm for automated segmentation of the wrist bones in early rheumatoid arthritis (ERA) patients on T2W fat-saturated MR images. As preliminary tests indicated that out-of-the-box segmentation CNN U-net performance was compromised by close apposition of wrist tendons and bone, we separated the volumes prior to segmentation by using classification CNN Inception V3 to group images with similar features. The classified images were then segmented by individually trained U-net. We trained the networks on 40 cases and tested them on 11 cases derived from an MR imaging dataset of 51 patients with varying severity of ERA. We obtained a wrist bone segmentation with an average dice similarity coefficient (DICE) of 0.888±0.014, when compared to a manually drawn label. These results are comparable to existing atlas-based methods. We have developed a fully automatic method to segment the wrist bones in ERA patients of varying severity directly from T2W fat-suppressed MR images. This compares well with manually drawn labels.

Validity and Responsiveness of Combined Inflammation and Combined Joint Damage Scores Based on the OMERACT Rheumatoid Arthritis MRI Scoring System (RAMRIS).

The RAMRIS [Outcome Measures in Rheumatology rheumatoid arthritis (RA) magnetic resonance imaging (MRI) Scoring system] is used in clinical RA trials. We have investigated methods to combine the RAMRIS features into valid and responsive scores for inflammation and joint damage. We used data from 3 large randomized early RA trials to assess 5 methods to develop a combined score for inflammation based on RAMRIS bone marrow edema, synovitis, and tenosynovitis scores, and a combined joint damage score based on erosions and joint space narrowing. Methods included unweighted summation, normalized summation, and 3 different variants of weighted summation of the RAMRIS features. We used a derivation cohort to calculate summation weights to maximize the responsiveness of the combined score. Construct validity of the combined scores was examined by assessing correlations to imaging, clinical, and biochemical measures. Responsiveness was tested by calculating the standardized response mean (SRM) and the relative efficiency of each score in a validation cohort. Patient characteristics, as well as baseline and followup RAMRIS scores, were comparable between cohorts. All combined scores were significantly correlated to other imaging, clinical, and biochemical measures. Inflammation scores combined by normalized and weighted summation had significantly higher responsiveness in comparison to unweighted summation, with SRM (95% CI) for unweighted summation 0.62 (0.51-0.73), normalized summation 0.73 (0.63-0.83), and weighted summation 0.74 (0.64-0.84). For the damage score, there was a trend toward higher responsiveness for weighted summation. Combined MRI scores calculated by normalized or weighted summation of individual MRI pathologies were valid and responsive.

Measuring lupus arthritis activity using contrasted high-field MRI. Associations with clinical measures of disease activity and novel patterns of disease

ObjectiveArthritis in SLE is poorly described, and there is no objective measure for quantification of arthritis. In this pilot study, we aim to assess the utility of the Rheumatoid Arthritis...

Are MRI-detected erosions specific for RA? A large explorative cross-sectional study

ObjectivesMRI is recommended in the diagnostic process of rheumatoid arthritis (RA) to detect joint damage early. MRI-detected erosions are also present in symptom-free controls, especially at older age. It is...

Efficacy of abatacept in patients with rheumatoid arthritis, as assessed by magnetic resonance imaging of bilateral hands.

To examine the efficacy of abatacept in patients with rheumatoid arthritis (RA) using magnetic resonance imaging (MRI) of bilateral hands. This prospective study included 35 RA patients. MRI of bilateral hands was performed at baseline and after 12months of treatment with intravenous abatacept. MRI images were scored for synovitis, osteitis, erosion and joint space narrowing (JSN) according to the RA MRI Scoring System (RAMRIS). The primary endpoint was the change in RAMRIS score from baseline. Repair of erosion was defined as a negative change in the erosion score that was greater than the smallest detectable changes (SDCs). Thirty-one patients completed the study. Median synovitis and osteitis scores showed statistically significant reductions at Month 12 when compared to baseline (synovitis score, -5.5 [P<0.0001]; osteitis score, -0.5 [P=0.03]). However, median erosion and JSN scores did not significantly change. At Month 12, 83% of patients showed no progression of erosion scores and repair of erosion was observed in 11% of patients. All patients with repair of erosion achieved functional remission (Health Assessment Questionnaire-Disability Index ≤0.5). The Simplified Disease Activity Index response rate at Month 1 was identified as an independent factor predicting changes in the erosion scores at Month 12. Abatacept treatment reduced synovitis and osteitis scores and did not worsen erosion and JSN scores at Month 12. Over 10% of patients experienced repair of erosion.

Cartilage quantification using contrast-enhanced MRI in the wrist of rheumatoid arthritis: cartilage loss is associated with bone marrow edema.

To quantify wrist cartilage using contrast MRI and compare with the extent of adjacent synovitis and bone marrow edema (BME) in patients with rheumatoid arthritis (RA). 18 patients with RA underwent post-contrast fat-suppressed T1weighted coronal imaging. Cartilage area at the centre of the scaphoid-capitate and radius-scaphoid joints was measured by in-house developed software. We defined cartilage as the pixels with signal intensity between two thresholds (lower: 0.4, 0.5 and 0.6 times the muscle signal, upper: 0.9, 1.0, 1.1, 1.2 and 1.3 times the muscle signal). We investigated the association of cartilage loss with synovitis and BME score derived from RA MRI scoring system. Cartilage area was correlated with BME score when thresholds were adequately set with lower threshold at 0.6 times the muscle signal and upper threshold at 1.2 times the muscle signal for both SC (rs=-0.469, p < 0.05) and RS (rs=-0.486, p < 0.05) joints, while it showed no significant correlation with synovitis score at any thresholds. Our software can accurately quantify cartilage in the wrist and BME associated with cartilage loss in patients with RA. Advances in knowledge: Our software can quantify cartilage using conventional MR images of the wrist. BME is associated with cartilage loss in RA patients.