Rheumatoid Arthritis Magnetic Resonance Imaging Scoring Research Articles

Repeatability and response to therapy of dynamic contrast-enhanced magnetic resonance imaging biomarkers in rheumatoid arthritis in a large multicentre trial setting

ObjectivesTo determine the repeatability and response to therapy of dynamic contrast-enhanced (DCE) MRI biomarkers of synovitis in the hand and wrist of rheumatoid arthritis (RA) patients, and in particular the performance of the transfer constant Ktrans, in a multicentre trial setting.MethodsDCE-MRI and RA MRI scoring (RAMRIS) were performed with meticulous standardisation at baseline and 6 and 24 weeks in a substudy of fostamatinib monotherapy in reducing synovitis compared with placebo or adalimumab. Analysis employed statistical shape modelling to avoid biased regions-of-interest, kinetic modelling and heuristic analyses. Repeatability was also evaluated.ResultsAt early study termination, DCE-MRI data had been acquired from 58 patients in 19 imaging centres. Ktrans intra-subject coefficient of variation (N = 14) was 30%. Ktrans change demonstrated inferiority of fostamatinib (N = 11) relative to adalimumab (N = 10) after 6 weeks (treatment ratio = 1.92, p = 0.003), and failed to distinguish fostamatinib from placebo (N = 10, p = 0.79). RAMRIS showed superiority of fostamatinib relative to placebo at 6 weeks (p = 0.023), and did not distinguish fostamatinib from adalimumab at either 6 (p = 0.175) or 24 (p = 0.230) weeks.ConclusionThis demonstrated repeatability of Ktrans and its ability to distinguish treatment groups show that DCE-MRI biomarkers are suitable for use in multicentre RA trials.Key Points• DCE-MRI biomarkers are feasible in large multicentre studies of joint inflammation.• DCE-MRI Ktransshowed fostamatinib inferior to adalimumab after 6 weeks.• Ktransrepeatability coefficient of variation was 30% multicentre.

Assessment of synovitis in rheumatoid arthritis by enhanced magnetic resonance imaging (OMERACT RAMRIS score) and power Doppler ultrasound: a comparative study

Background and objectives Disease activity in rheumatoid arthritis (RA) joints is conventionally assessed clinically in combination with the measurement of levels of biochemical surrogate markers. Plain radiography shows only late signs of preceding disease activity. Newer imaging modalities such as contrast-enhanced MRI and power Doppler ultrasonography (PDUS) may offer improved monitoring. The aim of the study was to compare the role of PDUS with enhanced MRI in the assessment and scoring of synovitis of the wrist and hand joints in RA patients. Patients and methods Fifty patients (39 female patients and 11 male patients) with RA were subjected to a PDUS study and enhanced MRI examination of the clinically dominant wrist and hand joints. The mean age of the patients was 45.3 years and mean disease duration was 6.2 years. Power Doppler score of synovitis was correlated and compared with MRI OMERACT score. Results PDUS detected increased vascularity within 30 (60%) wrist joints denoting active synovitis and MRI detected synovial enhancement within 38 (76%) wrist joints denoting active synovitis; both scoring systems agreed in the assessment of synovitis degree in 20 wrist joints. PDUS missed detection of synovitis in nine joints detected by MRI, seven of them estimated by MRI to be of mild activity (grade 1). PDUS detected synovial activity (increased vascularity) in metacarpophalangeal (MCP) joints of 21 patients, whereas MRI detected synovial activity (synovial enhancement) in MCP joints of nine patients. Both modalities agreed in eight patients as regards the total synovial activity score. Statistical analysis of these results showed a statistically significant correlation (P Conclusion Our results showed that both modalities are comparable and closely related in the assessment of synovial inflammatory process of the hand and wrist joints in RA patients.

Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis: an analysis by an OMERACT Task Force of pooled data from four randomised controlled trials

ObjectiveIn rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate...

Frequency of Arthritis-Like MRI Findings in the Forefeet of Healthy Volunteers Versus Patients With Symptomatic Rheumatoid Arthritis or Psoriatic Arthritis

The objective of the present study is to evaluate arthritis-like findings on MRI studies of the forefeet of healthy volunteers versus patients with symptomatic rheumatoid arthritis (RA) or psoriatic arthritis (PsA). Two observers analyzed MR images of the forefeet of 31 healthy volunteers, 30 patients with symptomatic RA, and 30 patients with symptomatic PsA, to identify MRI patterns of RA or PsA (e.g., bone marrow edema [BME], erosions, tenosynovitis, joint effusion, periarticular soft-tissue edema, or bony proliferations) on the basis of the Outcome Measures in Rheumatoid Arthritis Clinical Trial RA MRI scoring system and the PsA MRI scoring system. The Mann-Whitney test with Bonferroni correction was used for statistical analysis. Reader 1 found BME in 14 healthy volunteers (45%), whereas reader 2 found BME in 10 volunteers (32%). Tenosynovitis was observed by reader 1 in three healthy volunteers (10%). Joint effusion was found by reader 1 in seven healthy volunteers (23%) and by reader 2 in three volunteers (10%); the mean intensity grades for these findings were low (range, 1-1.33). Erosions, soft-tissue edema, and bony proliferations were not found in the forefeet of healthy volunteers. Reader 1 and reader 2 observed all arthritis-like features on the MR images of patients with RA. The percentages of patients with RA who had such MRI features, as identified by reader 1 and reader 2, respectively, were as follows: BME, 83% and 80%; erosions, 40% and 40%; tenosynovitis, 33% and 17%; effusion, 87% and 53%; soft-tissue edema, 20% and 27%; and bony proliferations, 3% and 3%. The percentages of patients with PsA who were found to have arthritis-like findings on MR images, as determined by reader 1 and reader 2, respectively, were as follows: BME, 70% and 67%; erosions, 20% and 20%; tenosynovitis, 57% and 50%; effusion, 70% and 37%; and soft-tissue edema, 60% and 53%. Bony proliferations were observed by reader 2 only in 7% of patients with PsA. The mean minimum intensity grade was 1 (for tenosynovitis in patients with RA, as observed by reader 2), whereas the maximum intensity grade was 2.53 (for erosions in patients with RA, as observed by reader 1). Tenosynovitis and soft-tissue edema were observed more frequently in patients with PsA than in patients with RA (p = 0.001-0.059). On the forefoot of healthy volunteers, mild BME is a common finding, and tenosynovitis and joint effusion are occasional findings. The frequency and intensity of arthritis-like findings on MRI are similar in patients with RA and PsA, with the exception of tenosynovitis and soft-tissue edema, which are more frequently observed in patients with PsA than in patients with RA.

Multimodal Diagnostic Approach to Monoarthritis of the Wrist

Objective: The aim of this study was to evaluate both the performance characteristics of magnetic resonance imaging (MRI) in the differential diagnosis of monoarthritis of the wrist and the predictive ability of the 1987 American College of Reumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria. Methods: The 29 patients with monoarthritis of the wrist retrospectively reviewed in this study underwent preoperative MRI with or without a white blood cell (WBC) scan. Their diagnoses were confirmed histologically after open synovectomy. Synovitis, bone erosion, and bone edema, as seen on MRI, were measured by 2 readers independently using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) system. Receiver operating characteristic (ROC) curves were used to calculate the cutoff differentiating rheumatoid arthritis (RA) from other diseases. The optimized cutoff point for each parameter was determined using Youden index. Results: The areas under the ROC curves for the synovitis, bone erosion, and bone edema scores were 0.892, 0.853, and 0.752, respectively. The cutoff values of these scores to predict RA were 5, 48, and 19, respectively. The sensitivity and specificity of the 1987 ACR criteria were 50% and 92% and those of the 2010 ACR/EULAR criteria were 60% and 75%. Conclusion: The OMERACT RAMRIS system provides a valuable tool to differentiate RA from tuberculosis and undifferentiated chronic monoarthritis in patients with wrist monoarthritis. A multimodal diagnostic approach using MRI, WBC scan, and histologic evaluation is recommended if the diagnosis cannot be established based on clinical, biochemical, and radiographic evaluations.

Relationship of patient-reported outcomes with MRI measures in rheumatoid arthritis

PurposeWe assessed whether MRI measures of synovitis, osteitis and bone erosion were associated with patient-reported outcomes (PROs) in a longitudinal clinical trial setting among patients with rheumatoid arthritis (RA).MethodsThis longitudinal...

Magnetic Resonance Imaging Bone Edema at Enrollment Predicts Rapid Radiographic Progression in Patients with Early RA: Results from the Nagasaki University Early Arthritis Cohort.

To clarify whether magnetic resonance imaging (MRI) bone edema predicts the development of rapid radiographic progression (RRP) in the Nagasaki University Early Arthritis Cohort of patients with early-stage rheumatoid arthritis (RA). Patients with early-stage RA (n = 76) were enrolled and underwent 1.5-T MRI of both wrists and finger joints. Synovitis, bone edema, and bone erosion were evaluated using the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS). RRP was defined as an annual increment > 3 at 1 year by the Genant-modified Sharp score of plain radiographs. A multivariate logistic regression analysis was performed to establish the risk factors for RRP. Median disease duration at enrollment was 3 months. RRP was found in 12 of the 76 patients at 1 year. A univariate analysis revealed that matrix metalloprotease-3, RAMRIS bone edema score, and RAMRIS bone erosion score were associated with RRP. Multivariate logistic regression analyses demonstrated that the RAMRIS bone edema score at enrollment (5-point increase, OR 2.18, 95% CI 1.32-3.59, p = 0.002) was the only independent predictor of the development of RRP at 1 year. A receiver-operating characteristic analysis identified the best cutoff value for RAMRIS bone edema score as 5. RRP was significantly rare among the patients with a RAMRIS bone edema score < 5 at enrollment (2 from 50 patients). Our findings suggest that MRI bone edema is closely associated with the development of RRP in patients with early-stage RA. Physicians should carefully control the disease activity when MRI bone edema is observed in patients with early RA.

Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis: clinical and MRI findings

ObjectiveTo assess early effects on joint structures of VX-509 in combination with stable disease-modifying antirheumatic drug (DMARD) therapy using MRI in adults with rheumatoid arthritis (RA).MethodsThis phase II, placebo-controlled, double-blind,...

Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial

ObjectiveTo investigate whether an intensive early rheumatoid arthritis (RA) treat-to-target (T2T) strategy could be improved through the use of musculoskeletal ultrasound (MSUS) assessment of disease activity.Methods111 newly diagnosed patients with...

Accurate quantitative assessment of synovitis in rheumatoid arthritis using pixel-by-pixel, time-intensity curve shape analysis.

To improve on the reproducibility and sensitivity of the assessment of patients with rheumatoid arthritis (RA), two semi-automated measurement methods of the area of enhancing pannus (AEP), based on thresholding (AEP_THRES) and pixel-by-pixel time-intensity curve analysis (AEP_TIC), were evaluated as an alternative for the gold-standard manual contouring method (AEP_MANUAL). 8 patients (7 females and 1 male) with RA of the wrist or finger joints participated in the study. A three-dimensional contrast-enhanced dynamic sequence was used at 3 T. After identifying the most relevant time-intensity curve (TIC) shape in terms of synovitis by comparing with the synovitis score using the RA-MRI scoring system, three different approaches for measuring the AEP were performed. Spearman's test of rank correlation was used to compare AEPs via two semi-automated methods (AEP_THRES and AEP_TIC) against manual segmentation (AEP_MANUAL) in the entire hand region as well as the wrist and the finger regions. The TIC shape of "washout after fast initial enhancement" had excellent correlation with synovitis score (r = 0.809). The correlation coefficient between AEP_TIC and AEP_MANUAL was evaluated to be better than that of AEP_THRES and AEP_MANUAL in the wrist region (AEP_THRES: r = 0.716, AEP_TIC: r = 0.815), whereas these were of comparable accuracy for the entire hand and the finger regions. This study suggests that TIC analysis may be an alternative to manual contouring for pannus quantification and provides important clinical information of the extent of the disease in patients with RA. TIC shape analysis can be applied for new quantitative assessment for RA synovitis in the wrist.

Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques

ObjectivesTo explore the effects of tofacitinib—an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)—with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early...

Ultrasound and magnetic resonance imaging correlation of the wrist and metacarpophalangeal joints in fifty consecutive patients of rheumatoid arthritis

Background: Gray-scale ultrasound and Power Doppler ultrasound (GSUS, PDUS) and contrast Magnetic Resonance Imaging (MRI) are the imaging modalities to detect the disease in this early stage of rheumatoid arthritis (RA). This study was conducted to observe the advantages and disadvantages of USG and MRI of wrist and metacarpophalangeal joints in patients with rheumatoid arthritis. Methods: Clinically diagnosed cases of RA were included. GSUS-PDUS and high field (1.5T) MRI with contrast were used by two assessors. The evaluation and scoring was done using the RAMRIS score. Other assessed parameters included Joint space narrowing, GSUS bone erosions, Gray scale USG synovial hypertrophy, MRI tenosynovitis and tenosynovitis on GSUS. Results: Total 50 patients (44 female, 6 male; age 18-76 years) with 100 joints and 400 Metacarpophalangeal joints (2nd to 5th) including 2300 bone areas were evaluated. GSUS, PDUS evaluation was equal to contrast MRI evaluation in detecting joint space narrowing, effusion, flexor tenosynovitis (except for FPL tendon), extensor tenosynovitis. Whereas synovial thickening was better picked up in GSUS, PDUS than on contrast MRI. Contrast MRI picked up more cases of bone erosions, triangular fibro cartilage lesions and active synovitis as compared to GSUS, PDUS. Bone marrow edema which indicates active ostitis could only be directly detected on contrast MRI. Conclusions: GSUS, PDUS can be used as radiological investigative modality for the diagnosis of cases of early rheumatoid arthritis specially for synovial thickening, joint effusion, flexor and extensor tenosynovitis.

Gout on CT of the feet: A symmetric arthropathy

The aim of this study was to assess the distribution of bone erosions in the feet of patients with gout using CT and thereby to test the hypothesis that gout is an asymmetric arthropathy. CT scans of both feet were obtained from 25 patients with chronic gout. CT scans were scored for bone erosion using a semi-quantitative method based on the rheumatoid arthritis MRI scoring system (RAMRIS). CT bone erosion was assessed at 22 bones in each foot (total 1,100 bones) by two independent radiologists. Symmetry was assessed by two methods: (i) comparing right and left foot scores for each patient; and (ii) calculating the proportion of paired joints with or without erosions. Observer agreement was excellent (intra-class correlation coefficient 0.92). In the group overall, the difference in scores between the feet was not significant (Student's t-test P = 0.8). In 17 of 25 patients, the difference in erosion scores between the two feet was less than the inter-observer difference. In 24 of 25 patients, the proportion of paired joints was greater than 0.5, indicating symmetric disease. Erosive disease from gout is, in fact, a symmetric process in our patient group. This finding is contrary to the established view of gout as an asymmetric arthritis and lends new insight into the behaviour of this common disease.

Clinical factors, anticitrullinated peptide antibodies and MRI-detected subclinical inflammation in relation to progression from clinically suspect arthralgia to arthritis.

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. 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. 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). 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.

Automated assessment of synovitis in 0.2 T magnetic resonance images of the wrist

According to the current recommendations in diagnosis of rheumatoid arthritis (RA), Magnetic Resonance (MR) images of wrist joints are used to evaluate three main types of lesions: synovitis, bone edema and bone erosions. In the clinical practice, the RA-related lesions seen in MR images are assessed manually with the semi-quantitative RAMRIS scoring system. In this paper we present an automated method for inflamed synovial membrane volume determination, based on the analysis of pre- and post-contrast MR images and segmentation of wrist bones seen in MR images. We found that the correlation between the automatically quantified volume of synovitis and RAMRIS scores was in the range from 0.76 to 0.87 for the total RAMRIS synovitis score. This can be compared with the correlation between the manually quantified volume of synovitis and RAMRIS scores which was in the range from 0.75 to 0.81 for the total synovitis score. The results of the study demonstrate that computer assisted methods for assessment of synovitis have great potential for clinical applications.

Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique

ObjectivesIn rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive...

Validity of early MRI structural damage end points and potential impact on clinical trial design in rheumatoid arthritis

ObjectiveTo evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials.MethodsIn...

The OMERACT MRI in Arthritis Working Group — Update on Status and Future Research Priorities

To provide an update on the status and future research priorities of the Outcome Measures in Rheumatology (OMERACT) magnetic resonance imaging (MRI) in arthritis working group. A summary is provided of the activities of the group within rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA), and its research priorities. The OMERACT RA MRI score (RAMRIS) evaluating bone erosion, bone edema (osteitis), and synovitis is now the standard method of quantifying articular pathology in RA trials. Cartilage loss is another important part of joint damage, and at the OMERACT 12 conference, we provided longitudinal data demonstrating reliability and sensitivity to change of the RAMRIS JSN component score, supporting its use in future clinical trials. The MRI group has previously developed a PsA MRI score (PsAMRIS). At OMERACT 12, PsAMRIS was evaluated in a randomized placebo-controlled trial of patients with PsA, demonstrating the responsiveness and discriminatory ability of applying the PsAMRIS to hands and feet. A hand OA MRI score (HOAMRIS) was introduced at OMERACT 11, and has subsequently been further validated. At OMERACT 12, good cross-sectional interreader reliability, but variable reliability of change scores, were reported. Potential future research areas were identified at the MRI session at OMERACT 12 including assessment of tenosynovitis in RA and enthesitis in PsA and focusing on alternative MRI techniques. MRI has been further developed and validated as an outcome measure in RA, PsA, and OA. The group will continue its efforts to optimize the value of MRI as a robust biomarker in rheumatology clinical trials.

Aiming for a simpler early arthritis MRI protocol: can Gd contrast administration be eliminated?

To evaluate whether intravenous gadolinium (Gd) contrast administration can be eliminated when evaluating synovitis and tenosynovitis in early arthritis patients, thereby decreasing imaging time, cost, and invasiveness. Wrist MRIs of 93 early arthritis patients were evaluated by two readers for synovitis of the radioulnar, radiocarpal, and intercarpal joints, according to the Rheumatoid Arthritis MRI Scoring method (RAMRIS), and for tenosynovitis in ten compartments. Scores of MRI images without Gd contrast enhancement were compared to scores obtained when evaluating all, including contrast-enhanced, MRI images as reference. Subsequently, a literature review and pooled analysis of data from the present and two previous studies were performed. At the individual joint/tendon level, sensitivity to detect synovitis without Gd contrast was 91 % and 72 % for the two readers, respectively, with a specificity of 51 % and 81 %. For tenosynovitis, the sensitivity was 67 % and 54 %, respectively, with a specificity of 87 % and 91 %. Pooled data analysis revealed an overall sensitivity of 81 % and specificity of 50 % for evaluation of synovitis. Variations in tenosynovitis scoring systems hindered pooled analyses. Eliminating Gd contrast administration resulted in low specificity for synovitis and low sensitivity for tenosynovitis, indicating that Gd contrast administration remains essential for an optimal assessment. • Eliminating gadolinium contrast administration results in low specificity for synovitis • For tenosynovitis, sensitivity is low without gadolinium contrast administration • Gadolinium contrast administration remains essential for evaluating synovitis and tenosynovitis in early arthritis.

What is the prevalence of MRI-detected inflammation and erosions in small joints in the general population? A collation and analysis of published data.

IntroductionMRI sensitively depicts erosions, bone marrow edema (BME) and synovitis in rheumatoid arthritis (RA). Recently developed European League Against Rheumatism (EULAR) recommendations stated that MRI is valuable to improve the certainty of a considered diagnosis and to detect structural damage at an early time point. However, these recommendations were mainly based on the data of patients with RA; prevalences of MRI features in the general population were not extensively explored. We reviewed the literature on MRI studies including symptom-free persons to assess the occurrence of MRI features.MethodsMedical literature databases up to September 2013 were systematically reviewed for symptom-free persons with MRI data on metacarpophalangeal, wrist and metatarsophalangeal joints. Data were extracted and summarised. When allowed because of comparable scanning and scoring protocols, a mean frequency of features was calculated.ResultsOf the 338 articles screened, 31 studies evaluated MRI findings in symptom-free persons (n=516 in total). Both the imaging techniques (<1/≥1 T, with/without contrast enhancement) and the scoring methods (non-validated or RA MRI score (RAMRIS)) varied widely, prohibiting direct comparisons of the results of many studies. 15 studies scored data according to RAMRIS; combining data of similar joint regions showed that erosions (RAMRIS ≥1) were present in 33–52% of symptom-free persons. Similarly, synovitis was present in 27% and BME in 0–16% of symptom-free persons. The prevalence of MRI-detected erosions increased with age.ConclusionsMRI features, erosions in particular, occur frequently in symptom-free persons. Before MRI can be implemented in the diagnostic process, larger studies should be conducted determining the degree and combination of MRI features that are disease specific.