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Objective: Inflammation around the tendons of the hand interosseous muscles (interosseous tendon inflammation [ITI]) was recently identified on magnetic resonance imaging (MRI) in a set of patients with rheumatoid arthritis (RA) and arthralgia. We conducted a large MRI study to assess the prevalence of ITI at diagnosis of RA and of other arthritides, as well as its relationship with clinical signs., Methods: A total of 1,205 patients presenting with various types of early arthritis between 2010 and 2020 underwent contrast-enhanced hand MRI as part of the prospective Leiden Early Arthritis Cohort. MRI was evaluated with blinding for clinical data, for ITI lateral of metacarpophalangeal (MCP) joints 2-5, and for synovitis/tenosynovitis/osteitis. We assessed ITI presence at baseline per diagnosis and its relationship with clinical characteristics (ie, presence of hand arthritis, increased acute phase reactants, and local joint swelling and tenderness). Logistic regression and generalized estimating equations were used with adjustment for age and established local inflammation features (synovitis/tenosynovitis/osteitis)., Results: A total of 36% of patients with early RA (n = 532) had ITI; this was similar in patients with anti-citrullinated protein antibody (ACPA)-negative RA (37%) and those with ACPA-positive RA (34%; P = 0.53). ITI occurred regularly in remitting seronegative symmetrical synovitis with pitting edema (60%) and connective tissue diseases (44%) and less frequently in undifferentiated arthritis (14%), psoriatic arthritis (14%), inflammatory osteoarthritis (8%), reactive arthritis (7%), crystal arthritis (7%), and peripheral spondylarthritis (4%). ITI occurred more often in diagnoses with frequent arthritis of the hands (P < 0.001) and increased acute-phase reactants (P < 0.001). Within RA, ITI occurred together with local MCP joint synovitis (odds ratio [OR] 2.4, 95% confidence interval [95% CI] 1.7-3.4), tenosynovitis (OR 2.4, 95% CI 1.8-3.3), and osteitis (OR 2.2, 95% CI 1.6-3.1) on MRI. Moreover, ITI presence was associated with local MCP joint tenderness (OR 1.6, 95% CI 1.2-2.1) and swelling (OR 1.8, 95% CI 1.3-2.6), independent of age and MRI-detected synovitis/tenosynovitis/osteitis., Conclusion: ITI occurs regularly in RA and other arthritides with preferential involvement of hand joints and increased acute-phase reactants. At the MCP joint level, ITI associates independently with joint tenderness and swelling. Hence, ITI is a newly identified inflamed tissue mainly found in arthritides with particularly extensive and symptomatic inflammation., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: 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., Methods: 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., Findings: 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])., Interpretation: 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., Funding: European Research Council and the Dutch Arthritis Society., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: MRI of small joints plays an important role in the early detection and early treatment of rheumatoid arthritis. Despite its sensitivity to demonstrate inflammation, clinical use is hampered by accessibility, long scan time, intravenous contrast, and consequent high costs. To improve the feasibility of MRI implementation in clinical practice, we introduce a modified Dixon sequence, which does not require contrast and reduces total acquisition time to 6 min. Because the reliability in relation to conventional MRI sequences is unknown, we determined this., Methods: In 29 consecutive early arthritis patients, coronal and axial T2-weighted modified Dixon acquisitions on 3.0 T MRI scanner were acquired from metacarpophalangeal 2-5 to the wrist, followed by the standard contrast-enhanced protocol on 1.5 T extremity MRI. Two readers scored osteitis, synovitis and tenosynovitis (summed as total MRI-inflammation), and erosions (all summed as total Rheumatoid Arthritis MRI Score (RAMRIS)). Intraclass correlation coefficients (ICCs) between readers, and comparing the two sequences, were studied. Spearman correlations were determined., Results: Performance between readers was good/excellent. Comparing modified Dixon and conventional sequences revealed good/excellent reliability: ICC for total MRI-inflammation score was 0.84 (95% CI:0.70-0.92), for erosions 0.90 (95% CI:0.79-0.96), and for the total RAMRIS score 0.88 (95% CI:0.77-0.94). The scores of total MRI-inflammation, total erosions, and total RAMRIS were highly correlated (ρ = 0.80, ρ = 0.81, ρ = 0.82, respectively)., Conclusion: The modified Dixon protocol is reliable compared to the conventional MRI protocol, suggesting it is accurate to detect MRI inflammation. The good correlation may be the first step towards a patient-friendly, short and affordable MRI protocol, which can facilitate the implementation of MRI for early detection of inflammation in rheumatology practice., (© 2022. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Magnetic resonance imaging (MRI) of the axial skeleton, spine, and sacroiliac (SI) joints is critical for the early detection and follow-up of inflammatory rheumatologic disorders such as axial spondyloarthritis, rheumatoid arthritis, and SAPHO/CRMO (synovitis, acne, pustulosis, hyperostosis, and osteitis/chronic recurrent multifocal osteomyelitis). To offer a valuable report to the referring physician, disease-specific knowledge is essential. Certain MRI parameters can help the radiologist provide an early diagnosis and lead to effective treatment. Awareness of these hallmarks may help avoid misdiagnosis and unnecessary biopsies. A bone marrow edema-like signal plays an important role in reports but is not disease specific. Age, sex, and history should be considered in interpreting MRI to prevent overdiagnosis of rheumatologic disease. Differential diagnoses-degenerative disk disease, infection, and crystal arthropathy-are addressed here. Whole-body MRI may be helpful in diagnosing SAPHO/CRMO., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objectives: The squeeze test of MTP joints is frequently used because it is easy and cheap. It is traditionally perceived as a test for synovitis. Besides classic intra-articular synovitis, also tenosynovitis and intermetatarsal bursitis (IMB) represent synovial inflammation, albeit juxta-articularly located. Both are frequently present in RA and occasionally in other arthritides. Therefore we hypothesized that tenosynovitis and IMB contribute to a positive MTP squeeze test., Methods: A cross-sectional study design was used. A total of 192 early arthritis patients and 693 clinically suspect arthralgia patients underwent the MTP squeeze test and forefoot MRI at first presentation. MRI measurements in age-matched healthy controls were used to define positivity for synovitis, tenosynovitis and IMB. Logistic regression was used., Results: In early arthritis patients, synovitis [odds ratio (OR) 4.8 (95% CI 2.5, 9.5)], tenosynovitis [2.4 (1.2, 4.7)] and IMB [1.7 (1.2, 2.6)] associated with MTP squeeze test positivity. Synovitis [OR 3.2 (95% CI 1.4, 7.2)] and IMB [3.9 (1.7, 8.8)] remained associated in multivariable analyses. Of patients with a positive MTP squeeze test, 79% had synovitis or IMB: 12% synovitis, 15% IMB and 52% both synovitis and IMB. In clinically suspect arthralgia patients, subclinical synovitis [OR 3.0 (95% CI 2.0, 4.7)], tenosynovitis [2.7 (1.6, 4.6)] and IMB [1.7 (1.2, 2.6)] associated with MTP squeeze test positivity, with the strongest association for synovitis in multivariable analysis. Of positive MTP squeeze tests, 39% had synovitis or IMB (10% synovitis, 15% IMB and 13% both synovitis and IMB)., Conclusion: Besides synovitis, IMB contributes to pain upon compression in early arthritis, presumably due to its location between MTP joints. This is the first evidence showing that MTP squeeze test positivity is not only explained by intra- but also juxta-articular inflammation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Identifying patients that will develop RA among those presenting with undifferentiated arthritis (UA) remains a clinical dilemma. Although MRI is helpful according to EULAR recommendations, this has only been determined in UA patients not fulfilling 1987 RA criteria, while some of these patients are currently considered as RA because they fulfil the 2010 criteria. Therefore, we studied the predictive value of MRI for progression to RA in the current UA population, i.e. not fulfilling RA classification criteria (either 1987 or 2010 criteria) and not having an alternate diagnosis. Additionally, the value of MRI was studied in patients with a clinical diagnosis of UA, regardless of the classification criteria., Methods: Two UA populations were studied: criteria-based UA as described above (n = 405) and expert-opinion-based UA (n = 564), i.e. UA indicated by treating rheumatologists. These patients were retrieved from a large cohort of consecutively included early arthritis patients that underwent contrast-enhanced MRI scans of hand and foot at baseline. MRIs were scored for osteitis, synovitis and tenosynovitis. Patients were followed for RA development during the course of 1 year. Test characteristics of MRI were determined separately for subgroups based on joint involvement and autoantibody status., Results: Among criteria-based UA patients (n = 405), 21% developed RA. MRI-detected synovitis and MRI-detected tenosynovitis were predictive for progression to RA. MRI-detected tenosynovitis was independently associated with RA progression (odds ratio (OR) 2.79; 95% CI 1.40, 5.58), especially within ACPA-negative UA patients (OR 2.91; 95% CI 1.42, 5.96). Prior risks of RA development for UA patients with mono-, oligo- and polyarthritis were 3%, 19% and 46%, respectively. MRI results changed this risk most within the oligoarthritis subgroup: positive predictive value was 27% and negative predictive value 93%. Similar results were found in expert-opinion-based UA (n = 564)., Conclusion: This large cohort study showed that MRI is most valuable in ACPA-negative UA patients with oligoarthritis; a negative MRI could aid in preventing overtreatment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2021 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: Intermetatarsal 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., Methods: A 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., Results: At 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)]., Conclusion: Approximately 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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Magnetic resonance imaging (MRI) of small joints sensitively detects inflammation. This inflammation, and tenosynovitis in particular, has been shown to predict rheumatoid arthritis (RA) development in arthralgia patients. These data have predominantly been acquired on 1.0-1.5 T MRI. However, 3.0 T is now commonly used in practice. Evidence on the comparability of these field strengths is scarce and has never included subtle inflammation in arthralgia patients or tenosynovitis. Therefore, we assessed the comparability of 1.5 T and 3.0 T in detecting subclinical inflammation in arthralgia patients., Method: A total of 2968 locations (joints, bones, tendon sheaths) in the hands and forefeet of 28 patients with small-joint arthralgia, at risk for RA, were imaged on both 1.5 and 3.0 T MRI. Two blinded readers independently scored erosions, osteitis, synovitis, and tenosynovitis, in line with the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS). Features were summed into inflammation (osteitis, synovitis, tenosynovitis) and RAMRIS (inflammation and erosions). Agreement was assessed with intraclass correlation coefficients (ICCs) for continuous scores and after dichotomization into presence or absence of inflammation, on patient and location levels., Results: Interreader ICCs were excellent (> 0.90). Comparing 1.5 and 3.0 T revealed an ICC of 0.90 for inflammation and RAMRIS. ICCs for individual inflammation features were: tenosynovitis 0.87 (95% confidence interval 0.74-0.94), synovitis 0.65 (0.24-0.84), and osteitis 0.96 (0.91-0.98). Agreement was 83% for inflammation and 89% for RAMRIS. Analyses on the location level showed similar results., Conclusion: Agreement on subclinical inflammation between 1.5 T and 3.0 T was excellent. Although synovitis scores were slightly different, synovitis often occurs simultaneously with other inflammatory signs, suggesting that scientific results on the predictive value of MRI-detected inflammation for RA, obtained on 1.5 T MRI, can be generalized to 3.0 T MRI.

Background: The forefoot is a preferential location for joint and tendon sheath inflammation in rheumatoid arthritis (RA). It also contains bursae, of which the intermetatarsal bursae have a synovial lining. Some small imaging studies suggested that intermetatarsal bursitis (IMB) and submetatarsal bursitis (SMB) are involved in RA, but their association has not been thoroughly explored. Healthy control studies suggested that lesion size might be relevant. We studied the relation between IMB and SMB in early RA, compared to other arthritides and healthy controls, and the relevance of lesion sizes., Methods: Six hundred and thirty-four participants were studied: 157 consecutive patients presenting with early RA, 284 other arthritides, and 193 healthy controls. All underwent unilateral contrast-enhanced MRI of the forefoot at presentation. Two readers independently scored IMB and SMB and measured transverse and dorsoplantar diameters, blinded to clinical data. Subsequently, consensus was reached. Intra-reader ICC was 0.89. Logistic regression models were used, and test characteristics were calculated., Results: IMB and SMB associated with RA independent of each other (P < 0.001) and independent of age, gender, BMI, RA-MRI inflammation, and anti-CCP-antibodies (P = 0.041). Sensitivity for RA of IMB was 69%, and for SMB 25%. Specificity for IMB was 70% compared to other arthritides, and 84% compared to healthy controls. For SMB, this was 94% and 97% respectively. Regarding lesion size, the groups had considerable overlap: no cut-off size for RA could be distinguished with high sensitivity and specificity., Conclusion: Intermetatarsal and submetatarsal bursitis associated with early rheumatoid arthritis, contributing to the emerging evidence that inflammation of juxta-articular soft tissues is an early feature of RA.

Objective: The Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is validated for hand MRI. Its reliability applied to metatarsophalangeal (MTP 1-5) joints is unknown and was studied in early arthritis and clinically suspect arthralgia., Methods: Patients underwent 1.5 Tesla MRI of MTP, metacarpophalangeal (MCP 2-5), and wrist joints. Two paired readers scored bone marrow edema (BME), synovitis, tenosynovitis, and erosions. Interreader reliability was assessed of 441 consecutive early arthritis patients at baseline, 215 by 2 readers, and the remaining 226 by 2 different readers. Two readers scored baseline MRI of 82 consecutive patients with clinically suspect arthralgia, and 40 randomly selected patients by 9 readers. Intrareader reliability was determined on a random set of 15 early arthritis patients, scored twice by 2 readers. For change scores, 30 early arthritis patients with baseline and 1-year followup MRI were scored by 2 readers. Intraclass correlation coefficients (ICC), Bland-Altman (BA) plots, and smallest detectable change (SDC) were determined. MRI data of MTP joints were compared to wrist and MCP joints., Results: Interreader ICC and mean scores in early arthritis were BME ICC 0.91-0.92 (mean 1.5 ± SD 2.6), synovitis 0.90-0.92 (1.3 ± 1.7), tenosynovitis 0.80-0.85 (1.1 ± 1.8), and erosions 0.88-0.89 (0.7 ± 1.0). In patients with clinically suspect arthralgia, ICC were comparable. Intrareader ICC for inflammatory MRI features were 0.84-0.98, for erosions 0.71 (reader 1), and 0.92 (reader 2). Change score ICC were ≥ 0.90, except erosions (0.77). SDC were ≤ 1.0. BA plots showed no systematic bias. Reliability scores of MTP joints were similar to MCP and wrist joints., Conclusion: Status and change MRI scores of BME, synovitis, tenosynovitis, and erosions of MTP joints can be assessed reliably by RAMRIS.

Background: The relationship between physical joint examination (PE) and MRI-detected inflammation in early inflammatory arthritis has mostly been studied in the hands. Physical examination of MTP joints is considered difficult, and for these joints, this relationship is unknown. Therefore, we studied the concordance of PE with MRI inflammation in MTP joints. Metacarpophalangeal (MCP) joints were included for comparison., Methods: One thousand seven hundred fifty-nine MTP(2-5) and 1750 MCP(2-5) joints of 441 consecutive patients with early arthritis underwent PE (for joint swelling) and MRI, all evaluated by two assessors. MRI was scored for synovitis, tenosynovitis, and osteitis (summed MRI inflammation). Synovial intermetatarsal bursae may enlarge upon inflammation and become palpable and were therefore also assessed. Analyses (frequencies, GEE) were performed on joint level., Results: PE and MRI were concordant in 79% of MTP joints. Of 1606 non-swollen MTP joints, 83% showed no MRI inflammation and 17% showed subclinical MRI inflammation. Of 153 swollen MTP joints, 48% had MRI inflammation and 52% (79 MTP joints) did not. Of these 79 swollen MTP joints without MRI inflammation, 31 showed intermetatarsal bursitis and 48 joints had none of these MRI abnormalities (this concerned 31% of swollen MTP joints). MTP swelling was statistically independently associated with tenosynovitis (OR 2.21, 95% CI 1.1-4.3) and intermetatarsal bursitis (OR 2.91, 95% CI 1.8-4.8). MTP joints showed subclinical inflammation less often than MCP joints (17% vs. 34%, P < 0.001). Swollen MTP joints showed MRI inflammation less often than swollen MCP joints (48% vs. 88%, P < 0.001)., Conclusions: The absence of swelling of MTP joints in early arthritis is mostly accompanied by the absence of MRI-detected inflammation. Swollen MTP joints are, in addition to synovitis, also explained by tenosynovitis and intermetatarsal bursitis and partly unexplained by MRI. Their clinical relevance must be determined in longitudinal studies.

Background Although tenosynovitis in the hands is associated with rheumatoid arthritis (RA), it is unknown whether tenosynovitis of the forefoot is associated with RA. Purpose To determine the anatomy of tendon sheaths of the forefoot and the relationship between MRI-detected tenosynovitis at metatarsophalangeal (MTP) joints and RA. Materials and Methods Fourteen forefeet of donated bodies were examined at flexor tendons and extensor tendons for the presence and course of tendon sheaths. In the prospective study between June 2013 and March 2016, newly presenting patients with RA, patients with other early arthritides, and healthy control participants all underwent MRI of unilateral MTP joints 1-5. MRI studies were scored by two independent readers for tenosynovitis, synovitis, and bone marrow edema. The association between the presence of these features and RA was examined by using logistic regression. Results Macroscopically, all extensor and flexor tendons crossing MTP joints demonstrated sheaths surrounding tendons. Microscopically, a synovial sheath was present. MRI evaluation was performed in 634 participants: 157 newly presenting patients with RA (109 women; mean age, 59 years ± 11 [standard deviation]), 284 patients with other early arthritides (158 women; mean age, 56 years ± 17), and 193 healthy control participants (136 women; mean age, 50 years ± 16). MRI-detected tenosynovitis was associated with RA, both when compared with patients with other arthritides (odds ratio [OR], 2.5; 95% confidence interval [CI]: 1.7, 3.9; P < .001) and healthy control participants (OR, 46; 95% CI: 14, 151; P < .001). The association was OR of 2.4 (95% CI: 1.5, 3.8; P < .001) for flexor tendons and OR of 3.1 (95% CI: 1.9, 5.2; P < .001) for extensor tendons. The sensitivity of tenosynovitis in RA was 65 of 157 (41%; 95% CI: 35%, 50%). The specificity for RA was 63 of 284 (78%; 95% CI: 72%, 82%) compared with other arthritides, and three of 193 (98%; 95% CI: 96%, 99%) compared with healthy control participants. Conclusion Tendons at metatarsophalangeal joints are surrounded by tenosynovium. MRI-detected tenosynovitis at metatarsophalangeal joints was specific for rheumatoid arthritis when compared with findings in patients with other arthritides and findings in healthy control participants. © RSNA, 2020 Online supplemental material is available for this article.

Objectives: Tenosynovitis (inflammation of the synovial lining of the sheath surrounding tendons) is frequently observed on MRI of early arthritis patients. Since visual assessment of tenosynovitis is a laborious task, we investigated the feasibility of automatic quantification of tenosynovitis on MRI of the wrist in a large cohort of early arthritis patients., Methods: For 563 consecutive early arthritis patients (clinically confirmed arthritis ≥ 1 joint, symptoms < 2 years), MR scans of the wrist were processed in three automatic stages. First, super-resolution reconstruction was applied to fuse coronal and axial scans into a single high-resolution three-dimensional image. Next, 10 extensor/flexor tendon regions were segmented using atlas-based segmentation and marker-based watershed. A measurement region of interest (ROI) was defined around the tendons. Finally, tenosynovitis was quantified by identifying image intensity values associated with tenosynovial inflammation using fuzzy clustering and measuring the fraction of voxels with these characteristic intensities within the measurement ROI. A subset of 60 patients was used for training and the remaining 503 patients for validation. Correlation between quantitative measurements and visual scores was assessed through Pearson correlation coefficient., Results: Pearson correlation between quantitative measurements and visual scores across 503 patients was r = 0.90, p < 0.001. False detections due to blood vessels and synovitis present within the measurement ROI contributed to a median offset from zero equivalent to 13.8% of the largest measurement value., Conclusion: Quantitative measurement of tenosynovitis on MRI of the wrist is feasible and largely consistent with visual scores. Further improvements in segmentation and exclusion of false detections are warranted., Key Points: • Automatic measurement of tenosynovitis on MRI of the wrist is feasible and largely consistent with visual scores. • Blood vessels and synovitis in the vicinity of evaluated tendons can contribute to false detections in automatic measurements. • Further improvements in segmentation and exclusion of false detections are important directions of future work on the path to a robust quantification framework.

Background: MRI-detected subclinical joint inflammation in the hand joints of patients with undifferentiated arthritis (UA) predicts progression to rheumatoid arthritis (RA). It is unknown if adding MRI of the foot increases predictive accuracy compared to the hand alone., Methods: 1.5-T contrast-enhanced MRI of the unilateral foot (MTP-1-5) and hand (MCP-2-5 and wrist) was performed in 123 patients presenting with UA (not fulfilling the 2010 RA criteria) and scored for bone marrow edema (BME), synovitis and tenosynovitis. Symptom-free controls (n = 193) served as a reference for defining an abnormal MRI. Patients were followed for RA development ≤ 1 year, defined as fulfilling the classification criteria or initiation of disease-modifying antirheumatic drugs because of the expert opinion of RA. The added predictive value of foot MRI to hand MRI was evaluated., Results: Fifty-two percent developed RA. Foot tenosynovitis was predictive (OR 2.55, 95% CI 1.01-6.43), independent of BME and synovitis (OR 3.29, 95% CI 1.03-10.53), but not independent of CRP and number of swollen joints (OR 2.14, 95% CI 0.77-5.95). Hand tenosynovitis was also predictive independent of BME and synovitis (OR 3.99, 95% CI 1.64-9.69) and independent of CRP and swollen joints (OR 2.36, 95% CI 1.04-5.38). Adding foot tenosynovitis to hand tenosynovitis changed the sensitivity from 72 to 73%, specificity from 59 to 54% and AUC from 0.66 to 0.64; the net reclassification index was - 3.5., Conclusion: MRI-detected tenosynovitis of the foot predicts progression to RA. However, adding MRI of the foot does not improve the predictive accuracy compared to MRI of the hand alone. In view of cost reduction, the performance of foot MRI for prognostic purposes in UA can be omitted.

Objective: MRI-detected inflammation is considered of diagnostic value for rheumatoid arthritis (RA), but its evaluation involves a time-consuming scoring of 61 joint-level features. It is not clear, however, which of these features are specific for RA and whether evaluating a subset of specific features is sufficient to differentiate RA patients. This study aimed to identify a subset of RA-specific features in a case-control setting and validate them in a longitudinal cohort of arthralgia patients., Methods: The difference in frequency of MRI-detected inflammation (bone marrow edema, synovitis, and tenosynovitis) between 199 RA patients and 193 controls was studied in 61 features across the wrist, metacarpophalangeal, and metatarsophalangeal joints. A subset of RA-specific features was obtained by applying a cutoff on the frequency difference while maximizing discriminative performance. For validation, this subset was used to predict arthritis development in 225 clinically suspect arthralgia (CSA) patients. Diagnostic performance was compared to a reference method that uses the complete set of 61 features normalized for inflammation levels in age-matched controls., Results: Subset of 30 features, mainly (teno)synovitis, was obtained from the case-control setting. Validation in CSA patients yielded an area of 0.69 (95% CI: 0.59-0.78) under the ROC curve and a positive predictive value (PPV) of 31%, compared to 0.68 (95% CI: 0.60-0.77) and 29% PPV of the reference method with 61 features., Conclusion: Subset of 30 MRI-detected inflammatory features, dominated by (teno)synovitis, offers a considerable reduction of scoring efforts without compromising accuracy for prediction of arthritis development in CSA patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: MRI 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 unclear if RA-specific MRI-detected erosions can be distinguished from 'physiological' erosions in symptom-free individuals. This study compared MRI-detected erosions of patients with RA with healthy controls and with other arthritides., Methods: 589 newly presenting patients with early arthritis (238 RA, 351 other arthritides) and 193 symptom-free controls underwent contrast-enhanced 1.5T MRI of unilateral metacarpophalangeal and metatarsophalangeal (MTP) joints. Total erosion score (according to the Rheumatoid Arthritis MRI Scoring System), number, severity, location of erosions and simultaneous presence of MRI-detected inflammation (synovitis and/or bone marrow oedema) were compared; participants were categorised in three age groups (<40, 40-59, ≥60)., Results: Patients with RA had statistically significant higher total erosion scores than controls but scores of individual persons largely overlapped. Grade ≥2 erosions and MTP5 erosions were specific for RA (specificity 98%-100% and 90%-98% for different age groups). MTP1 erosions were only specific if aged <40 (specificity 98%) and erosions with inflammation if aged <60 (specificity 91%-100%). ≥1 of the mentioned erosion characteristics were present in 29% of patients with RA. Comparing patients with RA with other arthritides revealed that grade ≥2 erosions and MTP5 erosions remained specific for RA (specificity ≥89%) as well as MTP1 erosions if aged <40 (specificity 93%), in contrast to erosions combined with inflammation (specificity 49%-85%)., Conclusions: Total erosion scores of individual persons were largely overlapping. Erosion characteristics specific for RA were identified, but were infrequently present. Caution is needed not to overestimate the value of MRI erosions in the diagnostic process., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Although infrequent, some rheumatoid arthritis (RA) patients achieve disease-modifying antirheumatic drug (DMARD)-free sustained remission. The absence of RA-specific autoantibodies, such as anticitrullinated protein antibodies (ACPA), is known to be associated with this outcome but further mechanisms underlying the chronic nature of RA are largely unknown. Magnetic resonance imaging (MRI)-detected bone marrow edema (BME), or osteitis, strongly predicts erosive progression and is associated with ACPA positivity. Therefore, we hypothesized that the presence of MRI-detected osteitis is also predictive of not achieving DMARD-free sustained remission and that the presence of osteitis mediates the association between ACPA and DMARD-free sustained remission., Methods: A 1.5 T unilateral hand and foot MRI was performed at disease presentation in 238 RA patients, evaluating BME, synovitis, and tenosynovitis (summed as MRI inflammation score). DMARD-free sustained remission, defined as the absence of clinical synovitis after DMARD cessation that persisted during the total follow-up, was assessed (median follow-up 3.8 years). Associations between the different MRI-detected inflammatory features and this outcome were studied. A mediation analysis was performed to study whether the presence of BME mediated the association between ACPA and DMARD-free sustained remission. Finally, patterns of MRI-detected inflammation with regard to DMARD-free sustained remission were studied using partial least squares (PLS) regression., Results: Forty-six (19.3%) patients achieved DMARD-free sustained remission. ACPA positivity associated independently with remission (hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.06-0.39). In contrast, no associations were observed between MRI-detected BME (HR 0.99, 95% CI 0.94-1.03), or other MRI inflammatory features, and achieving DMARD-free sustained remission. Thus, the presence of BME did not mediate the association between ACPA and DMARD-free sustained remission. Furthermore, a PLS analysis revealed that patients who did or did not achieve remission could not be distinguished by patterns of MRI-detected inflammation., Conclusions: At disease presentation, osteitis, as well as other MRI-detected inflammatory features, was not associated with achieving DMARD-free sustained remission over time. Thus, imaging predictors for joint damage and disease persistence differ. The processes mediating RA chronicity remain largely unsolved.

Both the fields of rheumatology and radiology are changing rapidly. Effective medication has become available for rheumatoid arthritis (RA) and transformed it from a progressive disabling disease into a chronic disease. Indications for magnetic resonance imaging (MRI) have changed accordingly, shifting toward early detection. There is also an overall increased clinical demand for high-end imaging. Together with improvement of MRI units and sequences, MRI protocols are adapted based on clinical indications. This article addresses (1) the clinical background and present role of MRI in early disease detection, (2) RA involvement of peripheral joints, (3) RA involvement of the spine, and (4) state-of-the-art RA MRI protocols. The key toward cost-effective MRI examination in RA is communication between radiologist and rheumatologist as well as awareness and knowledge of the basics and advancements in both fields., Competing Interests: Monique Reijnierse reports grants from Dutch Arthritis Foundation, during the conduct of the study. All the other authors have no conflict of interest to disclose., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: To investigate the feasibility of automatic quantification of bone marrow edema (BME) on MRI of the wrist in patients with early arthritis., Methods: For 485 early arthritis patients (clinically confirmed arthritis of one or more joints, symptoms for less than 2 years), MR scans of the wrist were processed in three automatic stages. First, super-resolution reconstruction was applied to fuse coronal and axial scans into a single high-resolution 3D image. Next, the carpal bones were located and delineated using atlas-based segmentation. Finally, the extent of BME within each bone was quantified by identifying image intensity values characteristic of BME by fuzzy clustering and measuring the fraction of voxels with these characteristic intensities within each bone. Correlation with visual BME scores was assessed through Pearson correlation coefficient., Results: Pearson correlation between quantitative and visual BME scores across 485 patients was r=0.83, P<0.001., Conclusions: Quantitative measurement of BME on MRI of the wrist has the potential to provide a feasible alternative to visual scoring. Complete automation requires automatic detection and compensation of acquisition artifacts. Magn Reson Med 79:1127-1134, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., (© 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: The use of hand and foot MRI in the diagnostic process of RA has been advocated. Recent studies showed that MRI is helpful in predicting progression from clinically suspect arthralgia (CSA) to clinical arthritis, and from undifferentiated arthritis (UA) to RA. Symptom-free persons can also show inflammation on MRI. This study aimed to evaluate if MRI findings in symptom-free volunteers are relevant when defining a positive MRI., Methods: Two hundred and twenty-five CSA patients and two hundred and one UA patients underwent MRI of MCP, wrist and MTP joints at baseline and were followed for 1 year on progression to arthritis and RA, respectively, as reported previously. MRI was considered positive if ⩾ 1 joint showed inflammation (called uncorrected definition), or if ⩾ 1 joint had inflammation that was present in < 5% of persons of the same age category at the same location (called 5% corrected definition). Test characteristics were compared for both definitions., Results: By using MRI data of symptom-free volunteers as reference, specificity of MRI-detected inflammation increased from 22 to 56% in CSA patients, and from 10 to 36% in UA patients. The sensitivity was not affected; it was 88 and 85% in CSA patients and 93 and 93% in UA patients. The accuracy also increased, from 32 to 60% in CSA patients and 22 to 44% in UA patients., Conclusion: The use of a reference population resulted in a substantial reduction of false-positive results, without influencing the sensitivity. Although common for other tests in medicine, this phenomenon is novel for MRI in the early detection of RA., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objective: Peripheral bone mineral density (BMD) may be decreased in early rheumatoid arthritis (RA) but it is unknown whether BMD loss emerges before arthritis is clinically apparent. We aimed to study whether BMD loss occurs in patients with clinically suspect arthralgia (CSA), and whether it is associated with progression to clinical arthritis and magnetic resonance imaging (MRI)-detected subclinical inflammation., Method: Patients with CSA had arthralgia for <1 year and were at risk of progressing to RA according to their rheumatologists. At baseline, a 1.5 T MRI was performed of unilateral metacarpophalangeal, wrist, and metatarsophalangeal joints, and scored on synovitis, bone marrow oedema, and tenosynovitis;. summing these features yielded the total MRI inflammation score. Digital X-ray radiogrammetry (DXR) was used to estimate BMD on two sequential conventional hand radiographs (mean interval between radiographs 4.4 months). The change in BMD was studied; BMD loss was defined as a decrease of ≥2.5 mg/cm 2 /month. Patients were followed for arthritis development for a median of 18.4 months., Results: In CSA patients (n = 108), change in BMD was negatively associated with age (β = -0.03, p = 0.007). BMD loss in CSA patients was associated with arthritis development [adjusted for age hazard ratio (HR) = 6.1, 95% confidence interval (CI) 1.7 to 21.4] and was most frequently estimated in the months before clinical arthritis development. The total MRI inflammation scores were associated with the change in BMD (adjusted for age β = -0.05, p = 0.047). The total MRI inflammation score and BMD loss were both independently associated with arthritis development (HR = 1.1, 95% CI 1.1 to 1.2, and HR = 4.6, 95% CI 1.2 to 17.2, respectively)., Conclusion: In CSA patients, severe BMD loss is associated with MRI-detectable subclinical inflammation and with progression to clinical arthritis.

Objectives: To assess the diagnostic value of MRI for early RA. In some RA patients, a classifiable diagnosis cannot be made at first presentation; these patients present with unclassified arthritis (UA). The use of MRI for early diagnosis of RA is recommended, yet the evidence for its reliability is limited., Methods: MRI of hand and foot was performed in 589 early arthritis patients included in the Leiden Early Arthritis Clinic (229 presented with RA, 159 with other arthritides and 201 with UA). Symptom-free controls provided a reference for defining an abnormal MRI. In preliminary investigations, MRI of patients who presented with RA was compared with MRI of symptom-free controls and of patients with other arthritides. Thereafter, the value of MRI in early RA diagnosis was determined in UA patients using the 1-year follow-up on fulfilling the 1987 RA criteria and start of disease-modifying drugs as outcomes., Results: Preliminary investigations were promising. Of the UA patients, 14% developed RA and 37% started disease-modifying treatment. MRI-detected tenosynovitis was associated with RA development independent of other types of MRI-detected inflammation [odds ratio (OR) = 7.5, 95% CI: 2.4, 23] and also independent of age and other inflammatory measures (swollen joints, CRP) (OR = 4.2, 95% CI: 1.4, 12.9). Within UA patients, the negative predictive value of abnormal tenosynovitis was 95% (95% CI: 89%, 98%) and the positive predictive value 25% (95% CI: 17%, 35%). The performance was best in the subgroup of UA patients presenting with oligoarthritis (18% developed RA): the positive predictive value was 36% (95% CI: 23%, 52%), the negative predictive value was 98% (95% CI: 88%, 100%), the sensitivity was 93% (95% CI: 70%, 99%) and the specificity was 63% (95% CI: 51%, 74%)., Conclusion: MRI contributes to the identification of UA patients who will develop RA, mostly in UA patients presenting with oligoarthritis., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objectives: MRI sensitively detects inflammation, but the clinical relevance of MRI-detected inflammation is undetermined in early arthritis. Therefore, the aim of this cross-sectional study was to investigate the association between MRI-detected inflammation of hands and feet and functional disability in early arthritis., Methods: Five hundred and fourteen early arthritis patients, consecutively included in the Leiden Early Arthritis Clinic, were studied. At baseline a unilateral 1.5 T MRI of the wrist, MCP and MTP joints was performed and functional disability was measured using the HAQ. MRIs were scored for tenosynovitis, synovitis and bone marrow oedema (BME) by two readers. The sum of these types of MRI-detected inflammation yielded the total MRI-inflammation score. Linear and nonlinear regression analyses were performed with HAQ as outcome., Results: The total MRI-inflammation score was associated with the HAQ score (β = 0.014, P < 0.001), as were tenosynovitis (β = 0.046, P < 0.001), synovitis (β = 0.039, P < 0.001) and bone marrow oedema scores (β = 0.015, P < 0.001) separately. Analysing these three types of MRI-detected inflammation in one multivariable model revealed that only tenosynovitis was independently associated with the HAQ score (β = 0.039, P < 0.001). Also after correction for age, gender, joint counts, CRP and auto-antibodies, this association remained significant (β = 0.034, P < 0.001). MRI-detected inflammation at wrists or MCP joints associated significantly with impairments in hand functioning (e.g. difficulties with opening milk cartons or jars). Exploring the relation between MRI-detected inflammation and HAQ scores showed no evidence of a floor effect, suggesting that even low scores of MRI-detected inflammation are functionally relevant., Conclusion: MRI-detected inflammation, and tenosynovitis in particular, is associated with functional disability. This demonstrates the functional relevance of MRI-detected inflammation in early arthritis., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Although MRI is recommended for diagnostic use in detecting joint inflammation, its value in clinical practice has not been settled. Older symptom-free persons show more MRI-detected inflammation in their hands and feet. Within arthritis patients, a similar effect could be present (a general age effect). The association of age with MRI inflammation could also be enhanced by disease (disease-dependent age effect). Because both effects could have diagnostic consequences, we evaluated the association between age-at-onset and MRI-detected inflammation in early arthritis and RA., Methods: Unilateral contrast-enhanced MRI of the MCP joint, wrist and MTP joints was performed in 589 newly presenting early arthritis patients, of whom 229 had RA. Bone marrow oedema, synovitis and tenosynovitis were summed, yielding the MRI inflammation score. MRI findings were associated with age and compared with those of 193 (previously reported) symptom-free controls., Results: Early arthritis and RA-patients had, respectively, 2.6 (95% CI: 2.3, 3.0, P < 0.001) and 3.7 times (95% CI: 3.2, 4.3, P < 0.001) higher MRI inflammation scores than controls (adjusted for age). At higher age of onset, early arthritis and RA patients had higher MRI inflammation scores (1.03/year, P < 0.001). A similar effect was observed in controls (1.03/year, P < 0.001). The interaction term age*group (arthritis/RA vs controls) was non-significant (P = 0.80 and P = 0.23), suggesting that the age effect was not disease dependent. At the joint level, older RA patients had more extended MRI inflammation, but the preferential locations were similar., Conclusion: Older age is associated with more MRI-detected inflammation, and the effect was similar in arthritis and controls. This age effect should be considered when interpreting hand and foot MRI for diagnostic purposes., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The use of magnetic resonance imaging (MRI)-detected inflammation and joint damage in the diagnosis of rheumatoid arthritis is recommended by a European League Against Rheumatism imaging task force. This recommendation is based on the sensitivity of MRI and not on specificity. Knowledge of the prevalence of MRI-detected features in symptom-free persons, however, is pivotal when considering MRI for diagnostic purposes., Methods: From November 2013 to December 2014, 196 symptom-free persons of different ages were recruited from the general population. Inclusion criteria were no history of inflammatory arthritis, no joint symptoms during the previous month, and no clinically detectable arthritis on physical examination. Contrast-enhanced MRIs of the dominant metacarpophalangeal (MCP), wrist, and metatarsophalangeal (MTP) joints were obtained using a 1.5T scanner and scored by 2 readers for synovitis, bone marrow edema, tenosynovitis, and erosions. For analyses at the joint level, MRI-detected inflammation was considered present if both readers scored the image as positive., Results: Of 193 persons scanned (ages 19-89 years), only 28% had no single inflammatory feature and 22% had no erosions. Primarily low-grade features were observed. All MRI features were positively correlated with age (P < 0.001). Preferential locations for synovitis were MCP2, MCP3, the wrists, and MTP1. Bone marrow edema was frequently present in MCP3, the scaphoid, and MTP1. Tenosynovitis was infrequent, except for in the extensor carpi ulnaris. Preferential locations for erosions were MCP2, MCP3, MCP5, the distal ulna, MTP1, and MTP5. Tables with age-, location-, and inflammation type-dependent frequencies were constructed. Simultaneous colocalized presence of synovitis, bone marrow edema, tenosynovitis, or erosions occurred., Conclusion: MRI-detected inflammation and erosions are prevalent in symptom-free persons from the general population, especially at older ages and at preferential locations., (© 2016, American College of Rheumatology.)

Background: In the population a high body mass index (BMI) has been associated with slightly increased inflammatory markers. Within rheumatoid arthritis (RA), however, a high BMI has been associated with less radiographic progression; this phenomenon is unexplained. We hypothesized that the phenomenon is caused by an inverse relationship between BMI and inflammation in hand and foot joints with RA. To explore this hypothesis, local inflammation was measured using magnetic resonance imaging (MRI) in early arthritis patients presenting with RA or other arthritides and in asymptomatic volunteers., Methods: A total of 195 RA patients, 159 patients with other inflammatory arthritides included in the Leiden Early Arthritis Clinic, and 193 asymptomatic volunteers underwent a unilateral contrast-enhanced 1.5 T MRI scan of metacarpophalangeal, wrist, and metatarsophalangeal joints. Each MRI scan was scored by two readers on synovitis, bone marrow edema (BME), and tenosynovitis; the sum yielded the total MRI inflammation score. Linear regression on log-transformed MRI data was used., Results: A higher BMI was associated with higher MRI inflammation scores in arthritides other than RA (β = 1.082, p < 0.001) and in asymptomatic volunteers (β = 1.029, p = 0.040), whereas it was associated with lower MRI inflammation scores in RA (β = 0.97, p = 0.005). Evaluating the different types of inflammation, a higher BMI was associated with higher synovitis, BME, and tenosynovitis scores in arthritides other than RA (respectively β = 1.084, p < 0.001, β = 1.021, p = 0.24, and β = 1.054, p = 0.003), but with lower synovitis and BME scores in RA (respectively β = 0.98, p = 0.047 and β = 0.95, p = 0.002)., Conclusions: Increased BMI is correlated with less severe MRI-detected synovitis and BME in RA. This might explain the paradox in RA where obesity correlates with less severe radiographic progression.

Introduction: Patients with clinically suspect arthralgia (CSA) have, according to their rheumatologists, an increased risk of rheumatoid arthritis (RA), but their actual outcome is unexplored. This longitudinal study investigated (1) progression from CSA to clinically detectable arthritis and (2) associations of clinical factors, serological factors (among which are anticitrullinated peptide antibodies (ACPAs)) and MRI-detected subclinical inflammation with arthritis development., Methods: 150 patients with CSA were followed for ≥6 months. At baseline, clinical and serological data were collected and unilateral 1.5 T-MRI of metacarpophalangeal (MCP), wrist and metatarsophalangeal (MTP) joints was made. MRI scoring was done according to the RA MRI scoring system. Subclinical MRI inflammation was defined based on MRI results of 193 symptom-free persons., Results: During follow-up (median=75 weeks, IQR=41-106 weeks), 30 patients developed clinical arthritis; 87% did so <20 weeks after inclusion. In multivariable analyses, age, localisation of initial symptoms in small and large joints (compared with small joints only), C-reactive protein level, ACPA-positivity and subclinical MRI inflammation significantly associated with arthritis development; ACPA and MRI inflammation were most strongly associated (HR (95% CI) respectively, 6.43 (2.57 to 16.05) and 5.07 (1.77 to 14.50)). After 1-year follow-up, 31% of the patients with MRI inflammation and 71% of the ACPA-positive patients with MRI inflammation had progressed to arthritis. Forty-three per cent of the patients that developed arthritis within 1 year were ACPA-negative; 78% of them had subclinical MRI inflammation at baseline. When MRI inflammation was absent arthritis development was infrequent (6% in all patients with CSA and 3% in ACPA-negative patients with CSA)., Conclusions: Subclinical MRI inflammation precedes clinical arthritis with a few months. Subclinical MRI inflammation is, independent of other factors such as ACPA, associated with arthritis development., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: In rheumatoid arthritis (RA) bone marrow edema (BME, osteitis) and anti-citrullinated protein antibodies (ACPA) are associated with radiographic progression. ACPA have been associated with BME, but it is unknown if this association is confined to ACPA and BME. We performed cross-sectional analysis of the association of ACPA, rheumatoid factor (RF) and anti-carbamylated protein (anti-CarP) antibodies with BME and other types of inflammation (synovitis, tenosynovitis) detected by magnetic resonance imaging (MRI)., Methods: Disease-modifying antirheumatic drug (DMARD)-naïve patients with early arthritis (n = 589), included in the Leiden Early Arthritis Clinic cohort, underwent contrast-enhanced 1.5 T MRI of unilateral wrist, metacarpophalangeal and metatarsophalangeal-joints at baseline. BME, synovitis and tenosynovitis were scored by two readers. ACPA, rheumatoid factor (RF) and anti-CarP were determined at baseline., Results: In univariable analyses ACPA-positive patients had higher BME scores than ACPA-negative patients (median 4.5 vs. 2.0, p < 0.001), but not more synovitis and tenosynovitis. Also RF (median 3.75 vs. 2.0, p < 0.001) and anti-CarP antibodies (median 3.5 vs. 2.5, p = 0.012) were associated with higher BME scores. Because the autoantibodies were concomitantly present, analyses were stratified for the presence of different autoantibody combinations. ACPA-positive (ACPA+), RF-negative (RF-), anti-CarP-negative (anti-CarP-) patients did not have higher BME-scores than ACPA-negative (ACPA-), RF-, anti-CarP- patients. However ACPA+, RF-positive (RF+), anti-CarP- patients and ACPA+, RF+, anti-CarP-positive (anti-CarP+) patients had higher BME scores than ACPA-, RF-, anti-CarP- patients (median 5.0 and 4.5 vs. 2.0, p < 0.001 and p < 0.001). ACPA levels were not associated with BME scores. Analyses within RA- and UA-patients revealed similar results., Conclusions: The presence of ACPA alone or ACPA level was not statistically significantly associated with BME scores, but the combined presence of ACPA and RF was associated with more BME. This suggests an additive role of RF to ACPA in mediating osteitis.

Objective: In patients with rheumatoid arthritis (RA), bone marrow edema (BME) scores are associated with development of erosions. However, little is known about the course and outcome of BME at bone level. We undertook this study to determine the association of BME and synovitis with the development of erosions in the same bone longitudinally., Methods: Using 1.5T magnetic resonance imaging at baseline and at 4- and 12-month follow-up, we studied 1,947 bones of the metacarpophalangeal, wrist, and metatarsophalangeal joints in 59 patients presenting with RA or undifferentiated arthritis. Scanning and scoring of BME, synovitis, and erosions were performed according to the Outcome Measures in Rheumatology Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system. We evaluated the relationship of the course of BME and synovitis with erosive progression at bone level during 1 year., Results: Of the bones showing BME at baseline (n = 203), BME persisted in 56%, disappeared in 39%, and disappeared and then reappeared in 5%. Stratified analyses at baseline revealed that BME was associated with erosive progression both in the presence and in the absence of local synovitis, with odds ratios (ORs) of 7.5 (95% confidence interval [95% CI] 3.8-14.9) and 6.9 (95% CI 1.9-25.6), respectively. However, local synovitis was not associated with erosive progression in the presence or in the absence of BME (ORs of 2.0 [95% CI 0.6-7.0] and 1.9 [95% CI 0.8-4.1], respectively). In multivariable generalized estimating equation analyses, persistent BME was strongly associated with erosive progression (OR 60.5 [95% CI 16.8-218.1]) in contrast to persistent synovitis (OR 1.3 [95% CI 0.4-4.4])., Conclusion: BME frequently persists during the first year. Persistent BME was strongly associated with erosive progression in the same bone, independently of local synovitis. No independent association was observed for persistent synovitis. These findings are relevant for comprehending the development of erosions in RA., (© 2016, American College of Rheumatology.)

Objectives: In daily practice, the squeeze test is used to screen for arthritis in metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints. This cross-sectional cohort study determined the diagnostic accuracy of this test., Methods: Patients referred with arthralgia of recent onset that had either a clinical suspicion for progression to arthritis or clinically apparent arthritis were studied. The main outcome was swelling at physical examination of ≥1 MCP or MTP joint. Joint inflammation detected at extremity MRI was the secondary outcome., Results: Both at MCP and MTP joints, a positive squeeze test associated with swollen joints (p<0.005). The sensitivity of the test at the MCP joints was 53%, specificity 82%, positive likelihood ratio (LR+) 3.0, negative likelihood ratio (LR-) 0.6 and area under the receiver operator characteristic curve (AUC) 0.68. At the MTP joints, the sensitivity was 54%, specificity 74%, LR+ 2.1, LR- 0.6 and AUC 0.64. With MRI-detected inflammation as outcome, the sensitivity and specificity were 39% and 86% and 31% and 69% for the test at the MCP and MTP joints, respectively., Conclusions: A positive squeeze test is associated with local joint inflammation but the sensitivity is low, indicating a high percentage of swollen joints with a negative squeeze test. When the test is used on its own, it is insufficient to detect early arthritis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: The western population is ageing. It is unknown whether age at diagnosis affects the severity of Rheumatoid Arthritis (RA), we therefore performed the present study., Method: 1,875 RA-patients (7,219 radiographs) included in five European and North-American cohorts (Leiden-EAC, Wichita, Umeå, Groningen and Lund) were studied on associations between age at diagnosis and joint damage severity. In 698 Leiden RA-patients with 7-years follow-up it was explored if symptom duration, anti-citrullinated-peptide-antibodies (ACPA), swollen joint count (SJC) and C-reactive-protein (CRP) mediated the association of age with joint damage. Fifty-six other RA-patients of the EAC-cohort underwent baseline MRIs of wrist, MCP and MTP-joints; MRI-inflammation (RAMRIS-synovitis plus bone marrow edema) was also evaluated in mediation analyses. Linear regression and multivariate normal regression models were used., Results: Analysis on the five cohorts and the Leiden-EAC separately revealed 1.026-fold and 1.034-fold increase of radiographic joint damage per year increase in age (β=1.026, 1.034, both p<0.001); this effect was present at baseline and persisted over time. Age correlated stronger with baseline erosion-scores compared to joint space narrowing (JSN)-scores (r=0.38 versus 0.29). Symptom duration, ACPA, SJC and CRP did not mediate the association of age with joint damage severity. Age was significantly associated with the MRI-inflammation-score after adjusting for CRP and SJC (β=1.018, p=0.027). The association of age with joint damage (β=1.032, p=0.004) decreased after also including the MRI-inflammation-score (β=1.025, p=0.021), suggesting partial mediation., Conclusion: RA-patients presenting at higher age have more severe joint damage; this might be partially explained by more severe MRI-detected inflammation at higher age.

Background: The phase of arthralgia is the earliest moment to clinically recognize patients who may develop Rheumatoid Arthritis (RA). Previous imaging studies in the arthralgia phase have shown that inflammation precedes RA development. It is unknown which symptoms/characteristics relate to subclinical joint inflammation as measured by MRI. Among all patients with arthralgia, those with clinically suspect arthralgia (CSA) are suspected to progress to arthritis according to the clinical judgement of their rheumatologists. We determined the symptoms/characteristics of patients with CSA who had inflammation on MRI., Methods: 102 patients with CSA and without clinical arthritis were included. They completed questionnaires, underwent joint counts and unilateral 1.5 T MRI of MCP joints 2-4, wrist and MTP joints 1-5. Synovitis, bone marrow oedema (BME) and tenosynovitis were scored according to the OMERACT rheumatoid arthritis MRI scoring system. Symptoms and signs were related to MRI inflammation (based on MRI scores in symptom-free controls; a sum of synovitis, BME and tenosynovitis scores ≥3 was considered positive). Whether certain clinical characteristics frequently occurred together with MRI inflammation was studied by partial least squares analysis., Results: MRI was performed in 93 patients with CSA, 44% of whom had subclinical MRI inflammation. Synovitis was the most prevalent inflammatory feature on MRI (20%). Patients with MRI inflammation were older and were more frequently positive for anti-citrullinated peptide antibodies than patients without MRI inflammation (p<0.001 and 0.049). In PLS analysis, including 16 clinical and serological characteristics as independent variables and MRI inflammation as dependent variable, no clear clusters of patients with and without MRI inflammation were identified., Conclusions: Subclinical inflammation as measured by MRI is present in 44% of patients with CSA. A combination of symptoms/characteristics incompletely differentiated patients with and without MRI inflammation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Baseline erosions are characteristic for rheumatoid arthritis (RA) and predictive for a severe disease course. The mechanisms leading to baseline erosions being a strong predictor for radiological progression are unknown. We aimed to increase this understanding by mediation analyses in an observational cohort and a cross-sectional MRI study., Methods: 3256 hands and feet radiographs of 653 early RA patients assessed during 7 years of disease were scored using the Sharp-van der Heijde method. Mediation models and multivariate regression analyses were used to explore the association between baseline erosions, other predictors and radiological damage over time. 603 joints (MCP2-5 and MTP1-5) of 67 RA patients underwent 1.5 T MRI at baseline. Data on MRI inflammation were compared with clinical inflammation and baseline radiological erosions., Results: Patients with baseline erosions had, at any point in time during 7 years, 3.45 times more joint damage than patients without erosions (p<0.001, 95% CI 3.00 to 3.98). Baseline erosions were an independent predictor and not a mediator between symptom duration, systemic or local clinical inflammation (erythrocyte sedimentation rate (ESR), swollen joint count (SJC)) or autoantibodies (anti-citrullinated-peptide antibodies, rheumatoid factor) and radiological damage. Subclinical MRI inflammation was studied in relation to erosions, revealing that 83% of the non-swollen joints with baseline erosions had subclinical MRI inflammation compared with 25% of the non-swollen joints without baseline erosions (OR 15.2 95% CI 3.1 to 102.1). The association between MRI inflammation and baseline erosions was independent of symptom duration, ESR, SJC and autoantibodies., Conclusions: Baseline erosions are a predictor for future joint damage, independent of known predictors as time, autoantibodies or clinical measurable inflammation. Subclinical inflammation is suggested as an underlying mechanism., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: MRI is increasingly used to measure inflammation in rheumatoid arthritis (RA) research, but the correlation to clinical assessment is unexplored. This study determined the association and concordance between inflammation of small joints measured with MRI and physical examination., Methods: 179 patients with early arthritis underwent a 68 tender joint count and 66 swollen joint count and 1.5T MRI of MCP (2-5), wrist and MTP (1-5) joints at the most painful side. Two readers scored synovitis and bone marrow oedema (BME) according to the OMERACT RA MRI scoring method and assessed tenosynovitis. The MRI data were first analysed continuously and then dichotomised to analyse the concordance with inflammation at joint examination., Results: 1790 joints of 179 patients were studied. Synovitis and tenosynovitis on MRI were independently associated with clinical swelling, in contrast to BME. In 86% of the swollen MCP joints and in 92% of the swollen wrist joints any inflammation on MRI was present. In 27% of the non-swollen MCP joints and in 66% of the non-swollen wrist joints any MRI inflammation was present. Vice versa, of all MCP, wrist and MTP joints with inflammation on MRI 64%, 61% and 77%, respectively, were not swollen. BME, also in case of severe lesions, occurred frequently in clinically non-swollen joints. Similar results were observed for joint tenderness., Conclusions: Inflammation on MRI is not only present in clinically swollen but also in non-swollen joints. In particular BME occurred in clinically non-inflamed joints. The relevance of subclinical inflammation for the disease course is a subject for further studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: We recently demonstrated that MRI inflammation is prevalent in clinically non-swollen joints of early arthritis patients. In this study, we assessed the relevance of this subclinical inflammation with regard to radiographic progression., Methods: 1130 joints (unilateral metacarpophalangeal 2-5, wrist and metatarsophalangeal 1-5) of 113 early arthritis patients underwent clinical examination and 1.5 T MRI at baseline, and radiographs at baseline and 1 year. Two readers scored the MRIs for synovitis, bone marrow oedema (BME) and tenosynovitis according to Rheumatoid Arthritis (RA) Magnetic Resonance Imaging (MRI) Scoring System (RAMRIS). Radiographic progression over 1 year was determined using the Sharp-van der Heijde scoring method., Results: On patient level, BME, synovitis and tenosynovitis were associated with radiographic progression, independent of known risk factors (p=0.003, 0.001 and 0.011, respectively). Of all non-swollen joints (n=932), 232 joints (26%) had subclinical inflammation (≥1 MRI-inflammation feature present). These joints were distributed among 91% of patients. Radiographic progression was present in 4% of non-swollen joints with subclinical inflammation compared to 1% of non-swollen joints without subclinical inflammation (relative risks (RR) 3.5, 95% CI 1.3 to 9.6). Similar observations were done for BME (RR5.3, 95% CI 2.0 to 14.0), synovitis (RR3.4, 95% CI 1.2 to 9.3) and tenosynovitis (RR3.0, 95% CI 0.7 to 12.7) separately., Conclusions: Radiographic progression was infrequent, but joints with subclinical inflammation had an increased risk of radiographic progression within year 1. This demonstrates the relevance of MRI-detected subclinical inflammation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To determine whether T1 post-gadolinium chelate images (T1Gd) can replace T2-weighted images (T2) for evaluating bone marrow oedema (BME), thereby allowing a shorter magnetic resonance imaging (MRI) protocol in rheumatoid arthritis (RA)., Material and Methods: In 179 early arthritis patients and 43 advanced RA patients, wrist and metacarpophalangeal joints were examined on a 1.5-T extremity MRI system with a standard protocol (coronal T1, T2 fat-saturated and coronal and axial T1 fat-saturated after Gd). BME was scored according to OMERACT RAMRIS by two observers with and without T2 images available. Agreement was assessed using intraclass correlation coefficients (ICCs) for semi-quantitative scores and test characteristics with T2 images as reference., Results: Agreement between scores based on T2 and T1Gd images was excellent ICC (0.80-0.99). At bone level, sensitivity and specificity of BME on T1Gd compared to T2 were high for both patient groups and both readers (all ≥80 %)., Conclusion: T1Gd and T2 images are equally suitable for evaluating BME. Because contrast is usually administered to assess (teno)synovitis, a short MRI protocol of T1 and T1Gd is sufficient in RA., Key Points: • Bone marrow oedema scores are equal on T2 and T1-Gd-chelate enhanced sequences. • Agreement between scores based on T2 and T1-Gd-chelate images was excellent. • Sensitivity and specificity for presence of bone marrow oedema were high. • A short protocol without T2 images suffices in rheumatoid arthritis patients.

Objective: Magnetic resonance imaging (MRI) is increasingly used in rheumatoid arthritis (RA) research. A European League Against Rheumatism (EULAR) task force recently suggested that MRI can improve the certainty of RA diagnosis. Because this recommendation may reflect a tendency to use MRI in daily practice, thorough studies on the value of MRI are required. Thus far no large studies have evaluated the accuracy of MRI to differentiate early RA from other patients with early arthritis. We performed a large cross-sectional study to determine whether patients who are clinically classified with RA differ in MRI features compared to patients with other diagnoses., Methods: In our study, 179 patients presenting with early arthritis (median symptom duration 15.4 weeks) underwent 1.5T extremity MRI of unilateral wrist, metacarpophalangeal, and metatarsophalangeal joints according to our arthritis protocol, the foot without contrast. Images were scored according to OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) by 2 independent readers. Tenosynovitis was also assessed. The main outcome was fulfilling the 1987 American College of Rheumatology (ACR) criteria for RA. Test characteristics and areas under the receiver-operator-characteristic curves (AUC) were evaluated. In subanalyses, the 2010 ACR/EULAR criteria were used as outcome, and analyses were stratified for anticitrullinated protein antibodies (ACPA)., Results: The ACR 1987 criteria were fulfilled in 43 patients (24.0%). Patients with RA had higher scores for synovitis, tenosynovitis, and bone marrow edema (BME) than patients without RA (p < 0.05). ACPA-positive patients had more BME (median scores 6.5 vs. 4.25, p = 0.016) than ACPA-negative patients. For all MRI features, the predictive value for the presence of RA was low (< 50%). For all MRI features the AUC were < 0.70. Patients who fulfilled ACR/EULAR 2010 criteria but not ACR87 criteria for RA had less synovitis than patients who were positive for RA according to both sets of criteria (p = 0.029)., Conclusion: Although patients with RA had higher scores of MRI inflammation and ACPA-positive patients had more BME, the severity of MRI inflammation assessed according to RAMRIS does not accurately differentiate patients with RA from other early arthritis patients.

Introduction: It is known that anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) has a preclinical phase. Whether this phase is also present in ACPA-negative RA is unknown. To determine this, we studied ACPA-negative arthralgia patients who were considered prone to progress to RA for local subclinical inflammation observed on hand and foot magnetic resonance imaging (MRI) scans., Methods: We studied a total of 64 ACPA-negative patients without clinically detectable arthritis and with arthralgia of the small joints within the previous 1 year. Because of the character of the patients' symptoms, the rheumatologists considered these patients to be prone to progress to RA. For comparisons, we evaluated 19 healthy, symptom-free controls and 20 ACPA-negative RA patients, who were identified according to the 1987 American Rheumatism Association criteria. All participants underwent MRI of unilateral wrist, metacarpophalangeal and metatarsophalangeal joints. Synovitis and bone marrow oedema (BME) were scored according to the OMERACT rheumatoid arthritis magnetic resonance imaging scoring system, and the scores were summed to yield the 'MRI inflammation score'. Scores were compared between groups. Among the ACPA-negative arthralgia patients, MRI inflammation scores were related to C-reactive protein (CRP) levels and the tenderness of scanned joints., Results: MRI inflammation scores increased progressively among the groups of controls and ACPA-negative arthralgia and RA patients (median scores = 0, 1 and 10, respectively; P < 0.001). The MRI inflammation scores of ACPA-negative arthralgia patients were significantly higher than those of controls (P = 0.018). In particular, the synovitis scores were higher in ACPA-negative arthralgia patients (P = 0.046). Among the ACPA-negative arthralgia patients, inflammation was observed predominantly in the wrist (53%). The synovitis scores were associated with CRP levels (P = 0.007) and joint tenderness (P = 0.026). Despite the limited follow-up duration, five patients developed clinically detectable arthritis. These five patients had higher scores for MRI inflammation (P = 0.001), synovitis (P = 0.002) and BME (P = 0.003) compared to the other patients., Conclusion: Subclinical synovitis was observed in the small joints of ACPA-negative arthralgia patients, and especially in patients whose conditions progressed to clinically detectable arthritis. This finding suggests the presence of a preclinical phase in ACPA-negative RA. Further longitudinal studies of these lesions and patients are required to confirm this hypothesis.

Purpose: To assess the frequency and site of subaxial spinal canal stenosis due to enhancing tissue in patients with rheumatoid arthritis., Materials and Methods: Data from 33 consecutive patients with rheumatoid arthritis were evaluated; these patients had undergone 1.5-T magnetic resonance imaging following gadolinium chelate administration, in combination with a frequency selective fat-suppression technique. Stenosis and enhancement were scored for each of six cervical spinal levels and were compared with results in a control population consisting of 16 patients with degenerative disease. Enhancement was scored as superficial or deep on the anterior and posterior sides from the cervical spinal cord. Differences between patient groups were tested by using the chi(2) test for trend and the Fisher exact test., Results: No significant difference was found in the frequency or severity of subaxial stenosis between rheumatoid arthritis and degenerative disease. Deep epidural enhancement was observed more often with rheumatoid arthritis than with degenerative disease both anterior (25 of 33 patients vs seven of 16 patients, respectively; P <.001) and posterior (24 of 33 patients vs two of 16 patients, respectively; P =.001) to the spinal cord. Enhancing stenosing tissue in rheumatoid arthritis frequently occurred anterior and posterior at the same time and at the same level, with segmental cufflike extension of enhancing tissue around the dural sac. Stenosing tissue enhanced more frequently with rheumatoid arthritis than with degenerative disease (22 of 33 vs four of 16 patients, respectively; P =.008)., Conclusion: In patients with rheumatoid arthritis, subaxial stenosis is frequently caused by enhancing epidural tissue. This enhancing tissue presumably represents pannus., (Copyright RSNA, 2004)

Objective: To determine whether MR imaging in flexion adds value relative to imaging in the neutral position with respect to displaying involvement of the subarachnoid space, brainstem and spinal cord., Design and Patients: T1-weighted MR images of the cervical spine in 42 rheumatoid arthritis patients with cervical spine involvement were obtained and analyzed prospectively. We assessed changes between images obtained in the neutral position and following active flexion, especially horizontal atlantoaxial and subaxial motion, presence or absence of brainstem compression, subarachnoid space involvement at the atlantoaxial and subaxial level and the cervicomedullary angle. Vertical atlantoaxial subluxation and the amount of pannus were correlated with motion and change in subarachnoid space., Results: The flexion images showed horizontal atlantoaxial motion in 21 patients and subaxial motion in one patient. The flexion view displayed brainstem compression in only one patient. Involvement of the subarachnoid space increased at the atlantoaxial level in eight (19%) patients (P=0.004) and at the level below C2 in five (12%) patients (P=0.03). There were no patients with a normal subarachnoid space in neutral position and compression in the flexed position. The cervicomedullary angle changed significantly with flexion. Vertical atlantoaxial subluxation and the amount of pannus did not show a significant correlation with motion or subarachnoid space involvement., Conclusion: MR imaging in the flexed position shows a statistically significant narrowing of the subarachnoid space at the atlantoaxial level and below C2. Cord compression is only observed on flexion views if the subarachnoid space in neutral position is already decreased. MR imaging in the flexed position might be useful, since subarachnoid space involvement may be an indicator for the development of neurologic dysfunction.

Objective: Comparison of clinically observed neurologic long tract signs in a heterogeneous group of patients with rheumatoid arthritis (RA), with morphologic abnormalities of the cervical spine as depicted on radiographs and magnetic resonance (MR) images., Design: The patients were prospectively assigned to one of three classes on the basis of their neurologic status. Lateral cervical spine radiographs and sagittal T1-weighted and gradient echo images were performed. The qualitative MR features evaluated were erosion of the dens and atlas, brain stem compression, subarachnoid space encroachment, pannus around the dens, appearance of the fat body caudal to the clivus, and the signal intensity of the pannus. The quantitative imaging parameters were the cervicomedullary angle and the distance of the dens to the line of McRae., Patients: Sixty-three consecutive patients with RA and subjective symptoms, especially neck or occipital pain, and/or clinical objective signs consistent with a compromised cervical cord were included in this study., Results and Conclusions: Damage documented with radiographs and MR imaging in patients with RA is often severe, even in those without neurologic signs (class 1). None of the abnormalities confined to the atlantoaxial level correlated significantly with neurologic classification. Subarachnoid space encroachment anywhere in the entire cervical spine did correlate significantly with neurologic classification.