An introduction to the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas

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

The EULAR–OMERACT rheumatoid arthritis MRI reference image atlas: the metacarpophalangeal joints

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

The development of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas

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

The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the wrist joint

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

The relationship between specific tissue lesions and pain severity in persons with knee osteoarthritis

SummaryIntroductionPain is the most common symptom in knee osteoarthritis (OA), a leading cause of chronic disability, and a major source of the disability attributable to OA in general. Pain severity in knee OA is variable, ranging from barely perceptible to immobilizing. The knee lesions that contribute to pain severity have received little attention.ObjectiveTo examine whether worse pathology of specific knee tissues – i.e. cartilage, bone (attrition, cysts, bone marrow lesions, and osteophytes), menisci (tears and subluxation), ligaments, and synovium (synovitis/effusion) – is associated with more severe knee pain.MethodsOne hundred and forty-three individuals were recruited from the community with primary (idiopathic) knee OA, with definite tibiofemoral osteophytes in at least one knee, and at least some difficulty with knee-requiring activity. Knee magnetic resonance (MR) images were acquired using coronal T1-weighted spin-echo (SE), sagittal fat-suppressed dual-echo turbo SE, and axial and coronal fat-suppressed, T1-weighted 3D-fast low angle shot (FLASH) sequences. The whole-organ magnetic resonance imaging (MRI) scoring (WORMS) method was used to score knee tissue status. Since summing tissue scores across the entire joint, including regions free of disease, may dilute the ability to detect a true relationship between that tissue and pain severity, we used the score from the worst compartment (i.e. with the poorest cartilage morphology) as our primary approach. Knee pain severity was measured using knee-specific, 100mm visual analogue scales. In analyses to evaluate the relationship between knee pain severity and lesion score, median quantile regression was used, adjusting for age and body mass index (BMI), in which a 95% CI excluding 0 is significant.ResultsThe increase in median pain from median quantile regression, adjusting for age and BMI, was significant for bone attrition (1.91, 95% confidence interval (CI) 0.68, 3.13), bone marrow lesions (3.72, 95% CI 1.76, 5.68), meniscal tears (1.99, 95% CI 0.60, 3.38), and grade 2 or 3 synovitis/effusion vs grade 0 (9.82, 95% CI 0.38, 19.27). The relationship with pain severity was of borderline significance for osteophytes and cartilage morphology and was not significant for bone cysts or meniscal subluxation. Ligament tears were too infrequent for meaningful analysis. When compared to the pain severity in knees with high scores for both bone attrition and bone marrow lesions (median pain severity 40mm), knees with high attrition alone (30mm) were not significantly different, but knees with high bone marrow lesion without high attrition scores (15mm) were significantly less painful.ConclusionIn persons with knee OA, knee pain severity was associated with subarticular bone attrition, bone marrow lesions, synovitis/effusion, and meniscal tears. The contribution of bone marrow lesions to pain severity appeared to require the presence of bone attrition

Assessment of the radioanatomic positioning of the osteoarthritic knee in serial radiographs: comparison of three acquisition techniques

SummaryObjectiveRecent studies using various standardized radiographic acquisition techniques have demonstrated the necessity of reproducible radioanatomic alignment of the knee to assure precise measurements of medial tibiofemoral joint space width (JSW). The objective of the present study was to characterize the longitudinal performance of several acquisition techniques with respect to long-term reproducibility of positioning of the knee, and the impact of changes in positioning on the rate and variability of joint space narrowing (JSN).MethodsEighty subjects were randomly selected from each of three cohorts followed in recent studies of the radiographic progression of knee osteoarthritis (OA): the Health ABC study (paired fixed-flexion [FF] radiographs taken at a 36-month interval); the Glucosamine Arthritis Intervention Trial (GAIT) (paired metatarsophalangeal [MTP] radiographs obtained at a 12-month interval), and a randomized clinical trial of doxycycline (fluoroscopically assisted semiflexed anteroposterior (AP) radiographs taken at a 16-month interval).Manual measurements were obtained from each radiograph to represent markers of radioanatomic positioning of the knee (alignment of the medial tibial plateau and X-ray beam, knee rotation, femorotibial angle) and to evaluate minimum JSW (mJSW) in the medial tibiofemoral compartment. The effects on the mean annualized rate of JSN and on the variability of that rate of highly reproduced vs variable positioning of the knee in serial radiographs were evaluated.ResultsParallel or near-parallel alignment was achieved significantly more frequently with the fluoroscopically guided positioning used in the semiflexed AP protocol than with either the non-fluoroscopic FF or MTP protocol (68% vs 14% for both FF and MTP protocols when measured at the midpoint of the medial compartment; 75% vs 26% and 34% for the FF and MTP protocols, respectively, when measured at the site of mJSW; P<0.001 for each). Knee rotation was reproduced more frequently in semiflexed AP radiographs than in FF radiographs (66% vs 45%, P<0.01). In contrast, the FF technique yielded a greater proportion of paired radiographs in which the femorotibial angle was accurately reproduced than the semiflexed AP or MTP protocol (78% vs 59% and 56%, respectively, P<0.01 for each). Notably, only paired radiographs with parallel or near-parallel alignment exhibited a mean rate of JSN (±SD) in the OA knee that was more rapid and less variable than that measured in all knees (0.186±0.274mm/year, standardized response to mean [SRM]=0.68 vs 0.128±0.291mm/year, SRM=0.44).ConclusionThis study confirms the importance of parallel radioanatomic alignment of the anterior and posterior margins of the medial tibial plateau in detecting JSN in subjects with knee OA. The use of radiographic methods that assure parallel alignment during serial X-ray examinations will permit the design of more efficient studies of biomarkers of OA progression and of structure modification in knee OA

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

Objective: In 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 the ability of early MRI findings to predict subsequent structural damage by X-ray. Methods: Pooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses. Results: Progression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively). Conclusions: Early changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs

Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial)

Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA

CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans