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Objective: Bone shape and bone marrow lesions (BMLs) represent different features of Magnetic resonance imaging (MRI)-detected subchondral pathology in osteoarthritis (OA). The aim of this study was to determine how these features are related and how they change in OA progression., Methods: 600 participants from the Osteoarthritis Initiative (OAI) FNIH Biomarkers Initiative were included, having Kellgren-Lawrence grade 1-3, at baseline and MRI data at baseline and 24 months. The associations between 3D quantitative bone shape vectors and presence of (MRI Osteoarthritis Knee Score) MOAKS semi-quantitative BMLs (total BML size ≥1) were analysed for femurs and tibias using linear regression. Responsiveness over 24 months was calculated for both features in four pre-defined progression groups and reported as standardised response means (SRMs). Multilevel models investigated the longitudinal relationship between change in BML size and change in bone shape., Results: Mean age was 61.5, 59% female and mean body mass index (BMI) 30.7. Correlation between baseline femur vector and BML was r = 0.28, P < 0.001. The presence of BMLs was associated with higher bone shape vector; coefficient (95% CI) 0.75 (0.54, 0.96) and 0.57 (0.38, 0.77) for femur and tibia respectively, both P < 0.001. After covariate adjustment, only the femur remained significant [coefficient 0.49, (95% CI 0.30, 0.68)]. Longitudinally bone vector demonstrated more responsiveness to change than BMLs (SRM 0.89 vs 0.13) while multilevel models revealed that increase in BML size was related to a more positive bone shape vector (representing worsening OA)., Conclusion: There is a relationship between bone shape and BMLs, with prevalence of BMLs associated with increasing OA bone shape. Bone shape demonstrated greater responsiveness than semi-quantitative BMLs., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine the association between bisphosphonate treatment with the change of periarticular bone area and three-dimensional (3D) shape in participants of the Osteoarthritis Initiative (OAI) study., Design: Using propensity score (PS) matching method in females, 48 bisphosphonate users and 105 non-users, who were matched for osteoarthritis (OA) and osteoporosis (OP) related factors were included. Baseline and 24-month magnetic resonance imaging (MRI)-based periarticular bone area and 3D shape measurements were used. The association between bisphosphonate intake and 24-month interval changes of the periarticular bone area and 3D shape were evaluated using paired Wilcoxon signed rank test. We used conditional logistic regression models for determining the association between bisphosphonate intake and periarticular bone change, defined using the standard deviation of difference (SDD) and reliable change index (RCI) methods. P-values have been adjusted for multiple comparisons using Benjamini & Hochberg procedure and false discovery rate (FDR)-adjusted P-values were reported., Results: The 24-month interval increases in the periarticular bone area in medial side of tibia were significantly greater in non-users than users (FDR-adjusted P-value: 0.002). There was an approaching significance trend for lower medial tibial periarticular bone area expansion in bisphosphonate users in comparison with non-users (For 1SDD change, odds ratio 95% confidence interval (OR (95% CI)): 0.514 (0.271-0.975), FDR-adjusted P-value: 0.085) (For 1.96RCI change, OR (95% CI): 0.552 (0.309-0.986), FDR-adjusted P-value: 0.085)., Conclusions: Bisphosphonate intake was associated with a reduction in the odds (approaching but not achieving significance) of expansion periarticular bone area, specifically in the medial tibial sub-region., (Published by Elsevier Ltd.)

Objective: As a wider variety of therapeutic options for osteoarthritis (OA) becomes available, there is an increasing need to objectively evaluate disease severity on magnetic resonance imaging (MRI). This is more technically challenging at the hip than at the knee, and as a result, few systematic scoring systems exist. The OMERACT (Outcome Measures in Rheumatology) filter of truth, discrimination, and feasibility can be used to validate image-based scoring systems. Our objective was (1) to review the imaging features relevant to the assessment of severity and progression of hip OA; and (2) to review currently used methods to grade these features in existing hip OA scoring systems., Methods: A systematic literature review was conducted. MEDLINE keyword search was performed for features of arthropathy (such as hip + bone marrow edema or lesion, synovitis, cyst, effusion, cartilage, etc.) and scoring system (hip + OA + MRI + score or grade), with a secondary manual search for additional references in the retrieved publications., Results: Findings relevant to the severity of hip OA include imaging markers associated with inflammation (bone marrow lesion, synovitis, effusion), structural damage (cartilage loss, osteophytes, subchondral cysts, labral tears), and predisposing geometric factors (hip dysplasia, femoral-acetabular impingement). Two approaches to the semiquantitative assessment of hip OA are represented by Hip OA MRI Scoring System (HOAMS), a comprehensive whole organ assessment of nearly all findings, and the Hip Inflammation MRI Scoring System (HIMRISS), which selectively scores only active lesions (bone marrow lesion, synovitis/effusion). Validation is presently confined to limited assessment of reliability., Conclusion: Two methods for semiquantitative assessment of hip OA on MRI have been described and validation according to the OMERACT Filter is limited to evaluation of reliability.

Knee osteoarthritis is associated with structural changes in the joint. Despite its many drawbacks, radiography is the current standard for evaluating joint structure in trials of potential disease-modifying osteoarthritis drugs. MRI is a non-invasive alternative that provides comprehensive imaging of the whole joint. Frequently used MRI measurements in knee osteoarthritis are cartilage volume and thickness; others include synovitis, synovial fluid effusions, bone marrow lesions (BML) and meniscal damage. Joint replacement is considered a clinically relevant outcome in knee osteoarthritis; however, its utility in clinical trials is limited. An alternative is virtual knee replacement on the basis of symptoms and structural damage. MRI may prove to be a good alternative to radiography in definitions of knee replacement. One of the MRI parameters that predicts knee replacement is medial compartment cartilage volume/thickness, which correlates with radiographic joint space width, is sensitive to change, and predicts outcomes in a continuous manner. Other MRI parameters include BML and meniscal lesions. MRI appears to be a viable alternative to radiography for the evaluation of structural changes in knee osteoarthritis and prediction of joint replacement.

Objective: Despite a growing body of Magnetic Resonance Imaging (MRI) literature in osteoarthritis (OA), there is little uniformity in its diagnostic application. We envisage in the first instance the definition requiring further validation and testing in the research setting before considering implementation/feasibility testing in the clinical setting. The objective of our research was to develop an MRI definition of structural OA., Methods: We undertook a multistage process consisting of a number of different steps. The intent was to develop testable definitions of OA (knee, hip and/or hand) on MRI. This was an evidence driven approach with results of a systematic review provided to the group prior to a Delphi exercise. Each participant of the steering group was allowed to submit independently up to five propositions related to key aspects in MRI diagnosis of knee OA. The steering group then participated in a Delphi exercise to reach consensus on which propositions we would recommend for a definition of structural OA on MRI. For each round of voting, ≥60% votes led to include and ≤20% votes led to exclude a proposition. After developing the proposition one of the definitions developed was tested for its validity against radiographic OA in an extant database., Results: For the systematic review we identified 25 studies which met all of our inclusion criteria and contained relevant diagnostic measure and performance data. At the completion of the Delphi voting exercise 11 propositions were accepted for definition of structural OA on MRI. We assessed the diagnostic performance of the tibiofemoral MRI definition against a radiographic reference standard. The diagnostic performance for individual features was: osteophyte C statistic=0.61, for cartilage loss C statistic=0.73, for bone marrow lesions C statistic=0.72 and for meniscus tear in any region C statistic=0.78. The overall composite model for these four features was a C statistic=0.59. We detected good specificity (1) but less optimal sensitivity (0.46) likely due to detection of disease earlier on MRI., Conclusion: We have developed MRI definition of knee OA that requires further formal testing with regards their diagnostic performance (especially in datasets of persons with early disease), before they are more widely used. Our current analysis suggests that further testing should focus on comparisons other than the radiograph, that may capture later stage disease and thus nullify the potential for detecting early disease that MRI may afford. The propositions are not to detract from, nor to discourage the use of traditional means of diagnosing OA., (Copyright © 2011 Osteoarthritis Research Society International. All rights reserved.)

Objective: In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools, integrating expert readers' experience with all available scoring tools and the published data comparing the different scoring systems, we iteratively developed the magnetic resonance imaging (MRI) Osteoarthritis Knee Score (MOAKS). The purpose of this report is to describe the instrument and its reliability., Methods: The MOAKS instrument refines the scoring of bone marrow lesions (BMLs) (providing regional delineation and scoring across regions), cartilage (sub-regional assessment), and refines the elements of meniscal morphology (adding meniscal hypertrophy, partial maceration and progressive partial maceration) scoring. After a training and calibration session two expert readers read MRIs of 20 knees separately. In addition, one reader re-read the same 20 MRIs 4 weeks later presented in random order to assess intra-rater reliability. The analyses presented here are for both intra- and inter-rater reliability (calculated using the linear weighted kappa and overall percent agreement)., Results: With the exception of inter-rater reliability for tibial cartilage area (kappa=0.36) and tibial osteophytes (kappa=0.49); and intra-rater reliability for tibial BML number of lesions (kappa=0.54), Hoffa-synovitis (kappa=0.42) all measures of reliability using kappa statistics were very good (0.61-0.8) or reached near-perfect agreement (0.81-1.0). Only intra-rater reliability for Hoffa-synovitis, and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement <75%., Conclusion: MOAKS scoring shows very good to excellent reliability for the large majority of features assessed. Further iterative development and research will include assessment of its validation and responsiveness., (Copyright © 2011 Osteoarthritis Research Society International. All rights reserved.)

Objectives: The aim of this study was to determine whether magnetic resonance imaging (MRI)-related entheseal changes including osteitis and extracapsular oedema could be used to differentiate between metacarpophalangeal (MCP) joint involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)., Methods: Twenty patients (10 each with early RA and PsA) had dynamic contrast-enhanced MRI (DCE-MRI) of swollen MCP joints. Synovitis and tenosynovitis was calculated using quantitative analysis including the degree and kinetics of enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone oedema were scored using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) proposals. Entheseal-related features including extracapsular soft tissue enhancement or regions of diffuse bone oedema were also evaluated., Results: MRI was not able to differentiate at the group level between both cohorts on the basis of entheseal-related disease but a subgroup of PsA patients had diffuse extracapsular enhancement (30%) or diffuse bone oedema (20%). The RA patient group had a greater degree of MCP synovitis (p<0.0001) and tenosynovitis than PsA patients (p<0.0001). There were no significant differences in either the total number of erosions (p = 0.315) or the presence of periarticular bone oedema (p = 0.105) between the groups., Conclusion: Although conventional MRI shows evidence of an enthesitis-associated pathology in the MCP joints in PsA, this is not sufficiently common to be of diagnostic utility.

Aim: MRI provides unparalleled visualisation of all the anatomical structures involved in the osteoarthritis (OA) process. There is a need for reliable methods of quantifying abnormalities of these structures. The aim of this work was to assess the reliability of a novel MRI scoring system for evaluating OA of the knee and explore the validity of the bone marrow lesion (BML) scoring component of this new tool., Methods: After review of the relevant literature, a collaborative group of rheumatologists and radiologists from centres in the UK and USA established preliminary anatomical divisions, items (necessarily broadly inclusive) and scaling for a novel semi-quantitative knee score. A series of iterative reliability exercises were performed to reduce the initial items, and the reliability of the resultant Boston-Leeds Osteoarthritis Knee Score (BLOKS) was examined. A further sample had both the BLOKS and WORMS (Whole Organ MRI Score) bone marrow lesion (BML) score performed to assess the construct validity (relation to knee pain) and longitudinal validity (prediction of cartilage loss) of each scoring method., Results: The BLOKS scoring method assesses nine intra-articular regions and contains eight items, including features of bone marrow lesions, cartilage, osteophytes, synovitis, effusions and ligaments. The scaling for each feature ranges from 0-3. The inter-reader reliability for the final BLOKS items ranged from 0.51 for meniscal extrusion up to 0.79 for meniscal tear. The reliability for other key features was 0.72 for BML grade, 0.72 for cartilage morphology, and 0.62 for synovitis. Maximal BML size on the BLOKS scale had a positive linear relation with visual analogue scale (VAS) pain, however the WORMS scale did not. Baseline BML was associated with cartilage loss on both BLOKS and WORMS scale. This association was stronger for BLOKS than WORMS., Conclusion: We have designed a novel scoring system for MRI OA knee, BLOKS, that demonstrates good reliability. Preliminary inspection of the validity of one of the components of this new tool supports the validity of the BLOKS BML scoring method over an existing instrument. Further iterative development will include validation for use in both clinical trials and epidemiological studies.

Objective: To examine the relationship between longitudinal fluctuations in synovitis with change in pain and cartilage in knee osteoarthritis., Methods: Study subjects were patients 45 years of age and older with symptomatic knee osteoarthritis from the Boston Osteoarthritis of the Knee Study. Baseline and follow-up assessments at 15 and 30 months included knee magnetic resonance imaging (MRI), BMI and pain assessment (VAS) over the last week. Synovitis was scored at 3 locations (infrapatellar fat pad, suprapatellar and intercondylar regions) using a semiquantitative scale (0-3) at all 3 time points on MRI. Scores at each site were added to give a summary synovitis score (0-9)., Results: We assessed 270 subjects whose mean (SD) age was 66.7 (9.2) years, BMI 31.5 (5.7) kg/m(2); 42% were female. There was no correlation of baseline synovitis with baseline pain score (r = 0.09, p = 0.17). The change in summary synovitis score was correlated with the change in pain (r = 0.21, p = 0.0003). An increase of one unit in summary synovitis score resulted in a 3.15-mm increase in VAS pain score (0-100 scale). Effusion change was not associated with pain change. Of the 3 locations for synovitis, changes in the infrapatellar fat pad were most strongly related to pain change. Despite cartilage loss occurring in over 50% of knees, synovitis was not associated with cartilage loss in either tibiofemoral or patellofemoral compartment., Conclusions: Change in synovitis was correlated with change in knee pain, but not loss of cartilage. Treatment of pain in knee osteoarthritis (OA) needs to consider treatment of synovitis.

Magnetic resonance imaging (MRI) can image all the tissues involved in the osteoarthritic joint-not just the cartilage but also the ligaments, synovium, menisci and subchondral bone. Despite these abilities, MRI does not have an established place in the investigation or management of osteoarthritis (OA). This chapter will overview the literature concerning MRI abnormalities in OA, and their relationship to structural progression and symptoms, in order to let the reader decide on the benefits of MRI in their particular practice. The evidence reviewed here will relate to knee OA, reflecting the vast preponderance of MRI studies in the knee.

Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both OA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful OA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the OA process and its response to therapy.

Objective: The aim of this study was to determine the responsiveness, effect size (ES) and smallest detectable difference (SDD) of two Magnetic Resonance Imaging (MRI) measures for osteoarthritis (OA) of the knee: a whole-organ semiquantitative evaluation and cartilage volume., Design: This analysis was performed on a dataset from a randomized, double-blind trial (Roche NI-15713) conducted in 1998 of a novel therapy in subjects with mild-moderate knee OA, with MRI at baseline and 6-month follow-up. The trial measurements included (1) cartilage volume measured using a proprietary software method; and (2) semiquantitative scoring of other parameters important for "whole organ" evaluation of OA knee joint pathology, using the Whole-Organ MRI Score (WORMS). The analysis initially examined the distributional characteristics of WORMS items, such as cartilage morphology. Standardized response mean (SRM), ES, and SDD between baseline and 6-month follow-up were then calculated in the whole group and the placebo group alone., Results: In general, the differences were small and this was reflected in the small ESs and SRMs. There was also a suggestion of a treatment effect with reduction in differences between baseline and follow-up in the treatment group., Conclusion: Of the MRI semiquantitative measures, cartilage morphology, synovitis and osteophytes appeared to be responsive to change and the focus of repeat measures should highlight these articular features. In general, the ESs and SRMs were small.

Objective: The ability to reliably quantify all the structural abnormalities in osteoarthritis (OA) of the knee is a long-standing goal of OA research. On December 5 and 6, 2002, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society, International held a Workshop for Consensus on Osteoarthritis Imaging in Bethesda, MD, with the aim of providing a state-of-the-art review of imaging outcome measures for OA of the knee. As part of the Workshop, data from previous clinical trials and epidemiological studies of OA were analysed with respect to the metrological properties of the measurement methods used. The following report outlines the results of analyses aimed at evaluating the internal construct validity of a whole-organ, ordinal (semi-quantitative) magnetic resonance imaging score (WORMS) using Rasch analysis. The fit of data to the Rasch model offers a measure of the validity of summing different items into a subscale score and the degree to which this score behaves as a unidimensional, interval level measurement tool., Methods: The Rasch model was applied in two OA studies. The first was a clinical cohort comprising OA knee subjects entering a clinical trial; study entry criteria included patients with at least moderate pain, radiographic osteophytes and a minimum of 1.5mm tibiofemoral joint-space width. The second cohort was from the Boston Osteoarthritis Knee Study, an observational cohort of subjects with symptomatic knee OA with pain on most days and a definite osteophyte in either the tibiofemoral or patellofemoral joints. Baseline WORMS scores from both studies were used for the Rasch analysis, performed with RUMM 2020 software., Results: There was a substantial proportion of subjects in both study populations with zero scores in several of the subscales of WORMS. Few of the subscales met the requirements of the Rasch measurement model when summated across all sites, and summations of some postulated compartmentally based sites also failed to fit the Rasch model. The existing scoring categories also required rescoring at many sites., Conclusion: There remain important issues in constructing outcome measurements that summate different features across multiple anatomical sites. The whole-organ scoring system evaluated here is no exception. Resolving these issues will improve the ability of imaging studies to assess complex pathological structural change.

Aim: To assess whether simple, limited section analysis can replace detailed volumetric assessment of synovitis in patients with osteoarthritis (OA) of the knee using contrast-enhanced magnetic resonance imaging (MRI)., Materials and Methods: Thirty-five patients with clinical and radiographic OA of the knee were assessed for synovitis using gadolinium-enhanced MRI. The volume of enhancing synovium was quantitatively assessed in four anatomical sites (the medial and lateral parapatellar recesses, the intercondylar notch and the suprapatellar pouch) by summing the volumes of synovitis in consecutive sections. Four different combinations of section analysis were evaluated for their ability to predict total synovial volume., Results: A total of 114 intra-articular sites were assessed. Simple linear regression demonstrated that the best predictor of total synovial volume was the analysis containing the inferior, mid and superior sections of each of the intra-articular sites, which predicted between 40-80% (r(2) = 0.396, p < 0.001 for notch; r(2) = 0.818, p < 0.001 for medial parapatellar recess) of the total volume assessment., Conclusions: The results suggest that a three-section analysis on axial post-gadolinium sequences provides a simple surrogate measure of synovial volume in OA knees.

This paper presents the metacarpophalangeal (MCP) joint magnetic resonance images of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. The illustrations include synovitis in the MCP joints (OMERACT RA magnetic resonance imaging scoring system (RAMRIS), grades 0-3), bone oedema in the metacarpal head and the phalangeal base (grades 0-3), and bone erosion in the metacarpal head and the phalangeal base (grades 0-3, and examples of higher grades). The presented reference images can be used to guide scoring of MCP joints according to the OMERACT RA MRI scoring system.

Based on a previously developed rheumatoid arthritis MRI scoring system (OMERACT 2002 RAMRIS), the development team agreed which joints, MRI features, MRI sequences, and image planes would best illustrate the scoring system in an atlas. After collecting representative examples for all grades for each abnormality (synovitis, bone oedema, and bone erosion), the team met for a three day period to review the images and choose by consensus the most illustrative set for each feature, site, and grade. A predefined subset of images (for example, for erosion--all coronal slices through the bone) was extracted. These images were then re-read by the group at a different time point to confirm the scores originally assigned. Finally, all selected images were photographed and formatted by one centre and distributed to all readers for final approval.

This paper outlines the most important pitfalls which are likely to be encountered in the assessment of magnetic resonance images of the wrist and metacarpophalangeal joints in patients with rheumatoid arthritis. Imaging artefacts and how these can be recognised using various sequences and views are discussed. Normal structures such as interosseous ligaments and nutrient foramina may appear prominent on certain images and need to be identified correctly. Pathological change in the rheumatoid hand involves many tissues and when substantial damage has occurred, it may be difficult to identify individual structures correctly. Bone erosion, bone oedema, synovitis, and tenosynovitis frequently occur together and in close proximity to each other, potentially leading to false positive scoring of any of these. Examples are given to illustrate the various dilemmas the user of this atlas may face when scoring the rheumatoid hand and suggestions are made to assist correct interpretation of what can be very complex images.

This article gives a short overview of the development and characteristics of the OMERACT rheumatoid arthritis MRI scoring system (RAMRIS), followed by an introduction to the use of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. With this atlas, MRIs of wrist and metacarpophalangeal joints of patients with rheumatoid arthritis can be scored for synovitis, bone oedema, and bone erosion, guided by standard reference images.

This paper presents the wrist joint MR images of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. Reference images for scoring synovitis, bone oedema, and bone erosions according to the OMERACT RA MRI scoring (RAMRIS) system are provided. All grades (0-3) of synovitis are illustrated in each of the three wrist joint areas defined in the scoring system--that is, the distal radioulnar joint, the radiocarpal joint, and the intercarpal-carpometacarpal joints. For reasons of feasibility, examples of bone abnormalities are limited to five selected bones: the radius, scaphoid, lunate, capitate, and a metacarpal base. In these bones, grades 0-3 of bone oedema are illustrated, and for bone erosion, grades 0-3 and examples of higher grades are presented. The presented reference images can be used to guide scoring of wrist joints according to the OMERACT RA MRI scoring system.

Imaging techniques such as musculoskeletal ultrasonography (MUS) and magnetic resonance imaging (MRI) are playing an increasingly important role in the assessment of patients with inflammatory arthritis. Such modalities are now used routinely in the evaluation of joint, tendon and soft tissue inflammation and bone damage in many early arthritis clinics. They have the ability to directly visualise, characterise and quantify the earliest inflammatory changes and have proved not only to be useful additional complimentary clinical tools to improve the speed and accuracy of diagnosis, direct appropriate treatment, monitor response to therapy, measure disease progression and outcome but also continue to contribute to our understanding of disease pathogenesis. These imaging methods may therefore offer a significant advantage as they endorse the principles of early diagnosis and optimal targeted therapy essential to providing the most favourable long term outcome for patients with inflammatory arthritis. This article reviews the current evidence supporting the role of MUS and MRI in the assessment of patients with inflammatory arthritis.

Advances in ultrasound (US) and magnetic resonance imaging (MRI) techniques have provided new methods for evaluating early rheumatoid arthritis (RA). Their diagnostic properties in terms of detecting primary pathology of RA (i.e., erosions, bone changes, synovitis, tenosynovitis, and effusion) are reviewed. High-resolution US plays a significant role in therapeutic and diagnostic procedures. MRI also assists in the understanding of RA pathogenesis and joint mechanics.

We examined inter-reader agreement of the revised OMERACT 5 Rheumatoid Arthritis MRI Score (RAMRIS v3). Magnetic resonance (MR) images of 10 sets of metacarpophalangeal (MCP) joints 2-5 and 8 sets of rheumatoid arthritis (RA) wrists [1.5 T, coronal and axial T1 and T2 spin-echo, +/- fat saturation (FS), +/- intravenous gadolinium (Gd)] were scored for (1) synovitis using a global score (0-3) and a direct measurement of synovial thickness (mm) and (2) three bone lesions: erosions, defects and edema, (score 0-10 by the volume of the lesion as a proportion of the "assessed bone volume" by 10% increments). Six readers from 5 multinational centers performed all scoring. Three statistical methods were used to analyze the data: (1) single-measure fixed effects intraclass correlations (sICC) and average-measure fixed effects ICC (avICC), (2) percentage exact and close agreement, and (3) the smallest detectable difference (SDD). The sICC were moderate to good (between 0.60 and 0.91) for half of the joint sites for the 2 synovitis scoring methods, and for bone erosions and bone edema. After adjusting for 6 readers, the avICC was very good to excellent (0.80-0.98) for two-thirds of the joint sites by lesion, excluding bone defects that performed relatively poorly, primarily because few readers scored these lesions. The aggregated scores with the best reliability were those with a wide range of scores, high ICC, low SDD, and low percentage SDD (< 33%). The metacarpophalangeal (MCP) bone erosion (sICC 0.58, avICC 0.89, %SDD +/- 27), wrist bone erosion scores (0.72, 0.94, +/- 31%), the wrist synovitis global (0.74, 0.94, +/- 32%), and synovial maximal thickness (0.6, 0.94, +/- 32%) met these conditions. MCP joint synovitis global (0.76, 0.95, +/-35%), MCP joint bone edema (0.63, 0.91, +/- 34%), and wrist bone edema (0.78, 0.95, +/- 38%) performed marginally less well. Bone defects performed poorly (MCP joint 0.18, 0.46, +/- 56%; wrist 0.06, 0.24, +/- 55%). The revised OMERACT 5 RAMRIS has acceptable inter-reader reliability for measures of disease activity (synovitis global and bone edema scores) and damage (bone erosion score). Whether the score is sensitive to change will be determined by its performance in longitudinal and intervention studies.

The rationale for an OMERACT Module on the use of magnetic resonance imaging (MRI) in the assessment of rheumatoid arthritis (RA) is outlined. This article also details the way in which the RA MRI Working Group developed and undertook a series of structured exercises to evaluate the reliability and sensitivity to change of the RA-MRI score (RAMRIS).

This article describes the 2002 OMERACT rheumatoid arthritis magnetic resonance image scoring system (RAMRIS) for evaluation of inflammatory and destructive changes in RA hands and wrists, which was developed by an international MRI-OMERACT group. MRI definitions of important RA joint pathologies, and a "core set" of basic MRI sequences for use in RA are also suggested.

The aim of this multireader, multicenter study was to assess the inter-reader reliability of the score in the assessment of disease status and progression. The exercise involved 10 sets of metacarpophalangeal (MCP, 2nd to 5th) joints and 10 sets of wrist magnetic resonance images that were scored by experienced readers from 5 international centers. Synovitis was scored for each site using a global score (0-3). Bone abnormalities were assessed at 8 MCP joint sites and 15 wrist sites according to proportion of bone volume (0-10 for erosions and defects and 0-3 for edema). Intraclass correlation coefficients (ICC) and smallest detectable differences for synovitis, erosions, and edema were acceptable, although better for status scores than progression scores. The agreement for MCP joints was better than wrists. Limited variation in the images for some findings resulted in low ICC. Bone defects had the poorest agreement and have been omitted from new scoring recommendations. Despite limited training, multicenter readers demonstrated acceptable levels of agreement.

Magnetic resonance image (MRI) scanning is a new method for imaging and quantifying joint inflammation and damage in rheumatoid arthritis (RA). Over the past 4 years, the OMERACT MR Imaging Group has been developing and testing the RA-MRI scoring system (RAMRIS) for use in RA. The OMERACT filter demands that an ideal outcome measure satisfy the elements of truth, discrimination, and feasibility. The RAMRIS as it currently stands incorporates measures of joint inflammation and damage including bone erosion, edema, and synovitis. Tendonitis has not been scored because of feasibility issues; joint space narrowing, reflecting cartilage damage, has also been excluded as reliability was low at the small joints of the hands. Anatomical coverage of the score is currently restricted to the wrists and hands but can provide a basis for a more comprehensive score. The MR measurement of synovitis correlates closely with histological evidence and work continues on validating MR erosions with reference to radiographic techniques. The RAMRIS has demonstrated good reliability for bone erosion and synovitis at the wrists and metacarpophalangeal joints subject to reader training, with slightly lower levels of reader agreement for bone edema. Reliability was less satisfactory in discriminating between 2 time points, and further work is required if the score is to be used to monitor change. Feasibility also needs to be considered for the practical application of the score, including the time taken for scanning and scoring, as well as cost and safety issues. The OMERACT RAMRIS provides a framework for scoring inflammation and damage in RA upon which further modifications can be built. It has been endorsed by the MRI working group and OMERACT 6 participants as useful for inclusion as an outcome measure in clinical trials.

Magnetic resonance imaging (MRI) allows direct visualization of inflammation and destruction in rheumatoid arthritis (RA) joints. However, MRI scoring methods have not yet been standardized or appropriately validated. Our aim was to examine interreader agreement for a simple system of scoring RA changes on MRI among 5 centers that had not undertaken intergroup calibration. MRI of RA wrist and metacarpophalangeal (MCP) joints were scored by experienced readers in 5 centers in different countries. In substudy 1, 5 sets of 2nd-5th MCP joints from UK [Technique A: 1.5 T, coronal and axial T1 and T2 spin-echo, -/+ fat saturation (FS), -/+ iv gadolinium (Gd)] were scored for synovitis (score 0-3) and bone lesions (0-3). In substudy 2, we evaluated 19 sets of 2nd-5th MCP joints [10 sets from UK (Technique A) and 9 sets from the US (Technique B: 1.5 T; coronal T1 spin-echo and T2* gradient-echo + FS, no Gd)] and 19 wrist joints [9 from the US (Technique B) and 10 from Denmark (Technique C: 1.0 T; coronal and axial T1 spin-echo, no FS, -/+ Gd)]. Synovitis (0-3), bone lesions (0-3), and joint space narrowing (JSN, 0-3) were scored in each MCP joint and in 3 different regions of the wrist. Bone erosions and lesions in each bone were scored 0-5. Substudy 1 served to test and redesign the score sheets. In substudy 2, the scores of synovitis and bone lesions by the 5 groups were the same or differed by only one grade in 73% and 85% of joints, respectively. On MRI that included 2 imaging planes and iv Gd (Techniques A and C), these rates were 86% (synovitis) and 97% (bone lesions). Corresponding intraclass correlation coefficients (quadratic weighted kappas) were 0.44-0.68, mean 0.58 (synovitis), and 0.44-0.69, mean 0.62 (bone lesion), i.e., in the moderate to good range. Unweighted kappa values were in the low to moderate range, generally lowest for JSN (< 0.20), better for synovitis and bone erosions, and best for bone lesions, being generally highest for MRI with 2 planes pre- and post-Gd and in MCPjoints compared with wrists. These preliminary results suggest that the basic interpretation of MRI changes in RA wrist and MCP joints is relatively consistent among readers from different countries and medical backgrounds, but that further training, calibration, and standardization of imaging protocols and grading schemes will be necessary to achieve acceptable intergroup reproducibility in assessing synovitis and bone destruction in RA multicenter studies.

Complementing the 3 papers that precede it, this paper explains the rationale for the activities of an OMERACT working party on magnetic resonance imaging (MRI) evaluation of rheumatoid arthritis (RA), sets out provisional recommendations for the acquisition and scoring of MRI of the hand and wrist in RA, and delineates some of the many residual problems that need to be addressed.

ObjectivePopulation-based osteoarthritis (OA) cohorts provide vital data on risk factors and outcomes of OA, however the methods to define OA vary between cohorts. We aimed to provide recommendations for combining knee and hip OA data in extant and future population cohort studies, in order to facilitate informative individual participant level analyses.MethodInternational OA experts met to make recommendations on: 1) defining OA by X-ray and/or pain; 2) compare The National Health and Nutrition Examination Survey (NHANES)-type OA pain questions; 3) the comparability of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) scale to NHANES-type OA pain questions; 4) the best radiographic scoring method; 5) the usefulness of other OA outcome measures. Key issues were explored using new analyses in two population-based OA cohorts (Multicenter Osteoarthritis Study; MOST and Osteoarthritis Initiative OAI).ResultsOA should be defined by both symptoms and radiographs, with symptoms alone as a secondary definition. Kellgren and Lawrence (K/L) grade ≥2 should be used to define radiographic OA (ROA). The variable wording of pain questions can result in varying prevalence between 41.0% and 75.4%, however questions where the time anchor is similar have high sensitivity and specificity (91.2% and 89.9% respectively). A threshold of 3 on a 0-20 scale (95% CI 2.1, 3.9) in the WOMAC pain subscale demonstrated equivalence with the preferred NHANES-type question.ConclusionThis research provides recommendations, based on expert agreement, for harmonising and combining OA data in existing and future population-based cohorts.

This paper presents an atlas for the Outcome Measures in Rheumatology Clinical Trials (OMERACT) thumb base osteoarthritis MRI scoring system (TOMS). The atlas includes reference images of each grade of each feature that is assessed in TOMS (synovitis grade 0-3, subchondral bone defects grade 0-3, osteophytes grade 0-3, cartilage assessment grade 0-3, subluxation and bone marrow lesions grade 0-3) in the first carpometacarpal and scapho-trapezio-trapezoid joint. The presented reference images can be used to guide scoring of thumb base MRIs in patients with hand osteoarthritis according to the OMERACT TOMS.

Objective: We conducted a systematic review in order to understand the relationship between imaging-visualised meniscus pathologies, hyaline cartilage, joint replacement and pain in knee osteoarthritis (OA).Design: A search of the Medline, Excerpta Medica database (EMBASE) and Cochrane library databases was performed for original publications reporting association between imaging-detected meniscal pathology (extrusion or tear/damage) and longitudinal and cross-sectional assessments of hyaline articular cartilage loss [assessed on magnetic resonance imaging (MRI)], incident joint replacement and pain (longitudinal and cross-sectional) in knee OA. Each association was qualitatively characterised by a synthesis of data from each analysis, based upon study design and quality scoring (including risk of bias assessment and adequacy of covariate adjustment using Cochrane recommended methodology).Results: In total 4,878 abstracts were screened and 82 publications were included (comprising 72 longitudinal analyses and 49 cross-sectional). Using high quality, well-adjusted data, meniscal extrusion and meniscal tear/damage were associated with longitudinal progression of cartilage loss, cross-sectional cartilage loss severity and joint replacement, independently of age, sex and body mass index (BMI). Medial and lateral meniscal tears were associated with cartilage loss when they occurred in the body and posterior horns, but not the anterior horns. There was a lack of high quality, well-adjusted meniscal pathology and pain publications and no clear independent association between meniscal extrusion or tear/damage with pain severity, progression in pain or incident frequent knee symptoms.Conclusion: Meniscal features have strong associations with cartilage loss and joint replacement in knee OA, but weak associations with knee pain. Systematic review PROSPERO registration number: CRD 42020210910. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40–75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren–Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300 mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75 mg, P = 0.165; vs 150 mg, P = 0.939; vs 300 mg, P = 0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis. [ABSTRACT FROM AUTHOR]

• Pain and the progressive loss of articular cartilage characterise knee osteoarthritis. • FORWARD was a phase II trial of sprifermin in patients with knee osteoarthritis. • This post-hoc analysis explored an advanced disease patient subgroup. • In the subgroup, sprifermin improved cartilage thickness and pain symptoms vs placebo. • The patient subgroup identified may represent a target population for future trials. To assess pain outcomes and cartilage thickness change in a subgroup at risk (SAR) of further progression in the FORWARD trial of knee osteoarthritis patients treated with sprifermin. Patients were randomised 1:1:1:1:1 to: sprifermin 100 µg every 6 months (q6mo), 100 µg q12mo, 30 µg q6mo, 30 µg q12mo, or placebo for 18 months. SAR was defined as baseline medial or lateral minimum joint-space width (mJSW) 1.5–3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score 40–90 units. Follow-up to 3 years was included in the analysis. Treatment benefit was explored by repeated measures, linear dose-effect trends by timepoint. The SAR comprised 161 (29%) of 549 patients. Mean difference (95% CI) in WOMAC pain at year 3 for sprifermin 100 µg q6mo vs placebo SAR was -8.75 (-22.42, 4.92) for SAR vs 0.97 (-6.22, 8.16) for the intent-to-treat population. SAR placebo patients lost more cartilage over 2 years than the modified ITT (mITT) placebo arm (mean change from baseline, mm [SD]: -0.05 [0.10] vs -0.02 [0.07]). Net total femorotibial joint thickness gain with sprifermin 100 µg q6mo (adjusted mean difference from placebo [95% CI] was similar in the SAR and in the mITT group: 0.06 [0.01, 0.11] vs 0.05 [0.03, 0.07]). Selection for low mJSW and moderate-to-high pain at baseline resulted in more rapid disease progression and demonstrated translation of structure modification (with maintained net benefit on total cartilage thickness) into symptomatic benefit. This subgroup may represent a target population for future trials. : NCT01919164. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of 'alternative' therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects. [ABSTRACT FROM AUTHOR]

Objectives: Meniscal pathology is integral to knee osteoarthritis (OA) and its progression; it provides a progression biomarker and a potential treatment target. Magnetic resonance imaging (MRI) demonstrates large heterogeneity in meniscal damage; this structural complexity means measurement is difficult. The aim of this study was to apply novel 3D image analysis to determine which meniscal pathologies demonstrated most change during OA progression.Methods: Knee images were selected from the progression cohort of the Osteoarthritis Initiative choosing participants with risk factors for medial OA progression. Medial and lateral menisci were manually segmented then analysed using a statistical shape model of the tibia as a reference surface. Responsiveness was assessed at 1 year using standardised response means (SRMs) for four constructs: meniscal volume, extrusion volume, thickness and tibial coverage; anatomical sub-regions of these constructs were also explored.Results: Paired images from 86 participants (median age 61.5, 49% female, 56% obese) were included. Reliability of the novel meniscal measurements was very good intraclass correlation coefficients (ICCs all > 0.98). Meniscal volume and extrusion demonstrated no significant change. Moderate responsiveness was observed for medial meniscus thickness (SRM -0.35) and medial tibial coverage (SRM -0.36). No substantial change was seen for the lateral meniscus measures. Sub-region analysis did not improve responsiveness; while greater change was seen in the posterior medial compartment, it was associated with increased variance of the change.Conclusions: The location of meniscal damage was consistently in the posterior medial region, and two measurements (thickness and tibial coverage) were most responsive. Meniscal measures should add to discriminatory power in OA progression assessment. [ABSTRACT FROM AUTHOR]

Objectives: To review the association between patellofemoral joint (PFJ) imaging features and patellofemoral pain (PFP).Design: A systematic review of the literature from AMED, CiNAHL, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PEDro, EMBASE and SPORTDiscus was undertaken from their inception to September 2014. Studies were eligible if they used magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US) or X-ray (XR) to compare PFJ features between a PFP group and an asymptomatic control group in people <45 years of age. A pooled meta-analysis was conducted and data was interpreted using a best evidence synthesis.Results: Forty studies (all moderate to high quality) describing 1043 people with PFP and 839 controls were included. Two features were deemed to have a large standardised mean difference (SMD) based on meta-analysis: an increased MRI bisect offset at 0° knee flexion under load (0.99; 95% CI: 0.49, 1.49) and an increased CT congruence angle at 15° knee flexion, both under load (1.40 95% CI: 0.04, 2.76) and without load (1.24; 95% CI: 0.37, 2.12). A medium SMD was identified for MRI patella tilt and patellofemoral contact area. Limited evidence was found to support the association of other imaging features with PFP. A sensitivity analysis showed an increase in the SMD for patella bisect offset at 0° knee flexion (1.91; 95% CI: 1.31, 2.52) and patella tilt at 0° knee flexion (0.99; 95% CI: 0.47, 1.52) under full weight bearing.Conclusion: Certain PFJ imaging features were associated with PFP. Future interventional strategies may be targeted at these features.Prospero Registration Number: CRD 42014009503. [ABSTRACT FROM AUTHOR]

To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13 277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion. [ABSTRACT FROM AUTHOR]

Summary Background Radiographic measures of osteoarthritis (OA) are based upon two dimensional projection images. Active appearance modelling (AAM) of knee magnetic resonance imaging (MRI) enables accurate, 3D quantification of joint structures in large cohorts. This cross-sectional study explored the relationship between clinical characteristics, radiographic measures of OA and 3D bone area (tAB). Methods Clinical data and baseline paired radiographic and MRI data, from the medial compartment of one knee of 2588 participants were obtained from the NIH Osteoarthritis Initiative (OAI). The medial femur (MF) and tibia (MT) tAB were calculated using AAM. ‘OA-attributable’ tAB (OA-tAB) was calculated using data from regression models of tAB of knees without OA. Associations between OA-tAB and radiographic measures of OA were investigated using linear regression. Results In univariable analyses, height, weight, and age in female knees without OA explained 43.1%, 32.1% and 0.1% of the MF tAB variance individually and 54.4% when included simultaneously in a multivariable model. Joint space width (JSW), osteophytes and sclerosis explained just 5.3%, 14.9% and 10.1% of the variance of MF OA-tAB individually and 17.4% when combined. Kellgren Lawrence (KL) grade explained approximately 20% of MF OA-tAB individually. Similar results were seen for MT OA-tAB. Conclusion Height explained the majority of variance in tAB, confirming an allometric relationship between body and joint size. Radiographic measures of OA, derived from a single radiographic projection, accounted for only a small amount of variation in 3D knee OA-tAB. The additional structural information provided by 3D bone area may explain the lack of a substantive relationship with these radiographic OA measures. [ABSTRACT FROM AUTHOR]

Summary: Objective: To summarize literature on the responsiveness and reliability of MRI-based measures of knee osteoarthritis (OA) structural change. Methods: A literature search was conducted using articles published up to the time of the search, April 2009. 1338 abstracts obtained with this search were preliminarily screened for relevance and of these, 243 were selected for data extraction. For this analysis we extracted data on reliability and responsiveness for every reported synovial joint tissue as it relates to MRI measurement in knee OA. Reliability was defined by inter- and intra-reader intra-class correlation (ICC), or coefficient of variation, or kappa statistics. Responsiveness was defined as standardized response mean (SRM) - ratio of mean of change over time divided by standard deviation of change. Random-effects models were used to pool data from multiple studies. Results: The reliability analysis included data from 84 manuscripts. The inter-reader and intra-reader ICC were excellent (range 0.8–0.94) and the inter-reader and intra-reader kappa values for quantitative and semi-quantitative measures were all moderate to excellent (range 0.52–0.88). The lowest value (kappa=0.52) corresponded to semi-quantitative synovial scoring intra-reader reliability and the highest value (ICC=0.94) for semi-quantitative cartilage morphology. The responsiveness analysis included data from 42 manuscripts. The pooled SRM for quantitative measures of cartilage morphometry for the medial tibiofemoral joint was −0.86 (95% confidence intervals (CI) −1.26 to −0.46). The pooled SRM for the semi-quantitative measurement of cartilage morphology for the medial tibiofemoral joint was 0.55 (95% CI 0.47–0.64). For the quantitative analysis, SRMs are negative because the quantitative value, indicating a loss of cartilage, goes down. For the semi-quantitative analysis, SRMs indicating a loss in cartilage are positive (increase in score). Conclusion: MRI has evolved substantially over the last decade and its strengths include the ability to visualize individual tissue pathologies, which can be measured reliably and with good responsiveness using both quantitative and semi-quantitative techniques. [Copyright &y& Elsevier]

Summary: Objective: To summarize literature on the concurrent and predictive validity of MRI-based measures of osteoarthritis (OA) structural change. Methods: An online literature search was conducted of the OVID, EMBASE, CINAHL, PsychInfo and Cochrane databases of articles published up to the time of the search, April 2009. 1338 abstracts obtained with this search were preliminarily screened for relevance by two reviewers. Of these, 243 were selected for data extraction for this analysis on validity as well as separate reviews on discriminate validity and diagnostic performance. Of these 142 manuscripts included data pertinent to concurrent validity and 61 manuscripts for the predictive validity review. For this analysis we extracted data on criterion (concurrent and predictive) validity from both longitudinal and cross-sectional studies for all synovial joint tissues as it relates to MRI measurement in OA. Results: Concurrent validity of MRI in OA has been examined compared to symptoms, radiography, histology/pathology, arthroscopy, CT, and alignment. The relation of bone marrow lesions, synovitis and effusion to pain was moderate to strong. There was a weak or no relation of cartilage morphology or meniscal tears to pain. The relation of cartilage morphology to radiographic OA and radiographic joint space was inconsistent. There was a higher frequency of meniscal tears, synovitis and other features in persons with radiographic OA. The relation of cartilage to other constructs including histology and arthroscopy was stronger. Predictive validity of MRI in OA has been examined for ability to predict total knee replacement (TKR), change in symptoms, radiographic progression as well as MRI progression. Quantitative cartilage volume change and presence of cartilage defects or bone marrow lesions are potential predictors of TKR. Conclusion: MRI has inherent strengths and unique advantages in its ability to visualize multiple individual tissue pathologies relating to pain and also predict clinical outcome. The complex disease of OA which involves an array of tissue abnormalities is best imaged using this imaging tool. [Copyright &y& Elsevier]

Summary: Objective: The Osteoarthritis Research Society International initiated a number of working groups to address a call from the US Food and Drug Administration (FDA) on updating draft guidance on conduct of osteoarthritis (OA) clinical trials. The development of disease-modifying osteoarthritis drugs (DMOADs) remains challenging. The Assessment of Structural Change (ASC) Working Group aimed to provide a state-of-the-art critical update on imaging tools for OA clinical trials. Methods: The Group focussed on the performance metrics of conventional radiographs (CR) and magnetic resonance imaging (MRI), performing systematic literature reviews for these modalities. After acquiring these reviews, summary and research recommendations were developed through a consensus process. Results: For CR, there is some evidence for construct and predictive validity, with good evidence for reliability and responsiveness of metric measurement of joint space width (JSW). Trials off at least 1 and probably 2 years duration will be required. Although there is much less evidence for hip JSW, it may provide greater responsiveness than knee JSW. For MRI cartilage morphometry in knee OA, there is some evidence for construct and predictive validity, with good evidence for reliability and responsiveness. The responsiveness of semi-quantitative MRI assessment of cartilage morphology, bone marrow lesions and synovitis was also good in knee OA. Conclusions: Radiographic JSW is still a recommended option for trials of structure modification, with the understanding that the construct represents a number of pathologies and trial duration may be long. MRI is now recommended for clinical trials in terms of cartilage morphology assessment. It is important to study all the joint tissues of the OA joint and the literature is growing on MRI quantification (and its responsiveness) of non-cartilage features. The research recommendations provided will focus researchers on important issues such as determining how structural change within the relatively short duration of a trial reflects long-term change in patient-centred outcomes. [Copyright &y& Elsevier]