Analysis of synovitis patterns in early RA supports the importance of joint-specific factors.

BACKGROUND: Rheumatoid arthritis (RA) is classically considered a systemic disorder, but the role of local factors in driving synovial inflammation is increasingly being recognized. These joint-specific factors may consequently modulate disease phenotype. OBJECTIVES: Our goal was to study the spatial distribution of swelling, tenderness and erosions in a large cohort of early RA (ERA) patients, to assess for patterns of simultaneously-involved joint clusters. We also aimed to investigate the link between arthritis localization and phenotypic features such as bone erosions and response to methotrexate therapy. METHODS: DMARD-naive patients from the ERA UCLouvain Brussels cohort were included. Forty-four joints were clinically assessed for swelling and tenderness before treatment, and 6 months later for methotrexate-treated patients. Clusters of joints were identified using Principal component analysis and Cramer's correlation coefficients. Frequency of bone erosions and joint-specific response to methotrexate were compared across different clusters. RESULTS: 452 ERA patients were included. Analysis of the spatial distribution of swelling and tenderness allowed for the identification of 3 joint clusters that showed significant simultaneous involvement: (i) MTP1-5 joints, (ii) hand joints (MCPs and PIPs), and (iii) larger joints. These clusters were associated with different susceptibility to bone erosions and distinct clinical features, but similar local response (joint swelling resolution) to methotrexate. CONCLUSION: This is the first study investigating the spatial distribution of arthritis in a large cohort of early RA using an unbiased approach. We identify clusters of simultaneously involved joints, supporting the importance of local factors in driving synovitis in RA.

Increased alcohol intake is associated with radiographic severity of knee and hand osteoarthritis in men.

Observational studies have shown controversial associations between alcohol intake and radiographic osteoarthritis (OA). This study investigated whether this association was causal using a Mendelian randomization (MR) study in a population-based cohort in Korean. The study enrolled 2429 subjects (1058 men, 1371 women) from the Dong-gu Study. X-rays of the hand and knee joints were scored using a semi-quantitative grading system to calculate the total score of the hand and knee joints. ALDH2 rs671 genotyping was performed by high-resolution melting analysis. MR instrumental variable analysis and observational multivariable regression analysis were used to estimate the association between genetically predicted alcohol intake and the radiographic severity of OA. Subjects with the G/G genotype had a higher current alcohol intake than those with the G/A and A/A genotypes in both men and women (all P < 0.001). Men with the G/G genotype had higher total knee (P < 0.001) and hand scores (P = 0.042) compared to those with the G/A and A/A genotypes after adjusting for age and body mass index, but not in women. In the observational multivariable regression analysis, each alcohol drink per day in men was associated with increased knee (P = 0.001) and hand joint scores (P = 0.013) after adjustment, but not in women. In our MR analysis, utilizing ALDH2 rs671 genotypes as instrumental variables for alcohol consumption, has shown a significant link between each additional daily alcohol drink and increased radiographic joint severity in men.

2023 EULAR classification criteria for hand osteoarthritis.

OBJECTIVES: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features. METHODS: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. RESULTS: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. CONCLUSIONS: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology.

Gender and age differences in the associations between cortical thickness and hand osteoarthritis severity: data from the Osteoarthritis Initiative.

OBJECTIVE: To evaluate gender differences in the association between metacarpal cortical thickness (Tcort)-a surrogate for bone density-and severity of radiographic hand osteoarthritis (HOA) in a longitudinal observational study. METHOD: Hand radiographs of 3575 participants (2039 F/1536 M) from the Osteoarthritis Initiative were assessed at baseline and 48 months. A reader used a semi-automated software tool to calculate Tcort, a measurement of the cortical thickness, for metacarpals 2-4. Average Tcort at baseline and change in Tcort from baseline to 48 months was determined and stratified by gender and age for 7 5-year age groups. Spearman's rank correlation coefficients were calculated for the association of baseline Tcort and 2 measures of baseline HOA severity: the sum of Kellgren-Lawrence (KL) grade and total number of joints with radiographic HOA. Longitudinally, logistic regression was used to assess the relationship of Tcort loss to new finger joint radiographic HOA, increase in KL grades, and incident hand pain. RESULTS: Male Tcort was higher than females. Significant correlations between Tcort and radiographic severity were noted for women but not men, with stronger associations among women >60 years (rho = -0.25; 95% confidence interval (CI) = -0.31 to -0.19). Statistically significant associations were seen between Tcort change and radiographic osteoarthritis change among women but not men, with substantial gender differences for Tcort change, particularly ages 50 to 70 years (p < 0.01; e.g., Tcort change ages 55 to <60: males = -0.182 (0.118), females = -0.219 (0.124)). CONCLUSION: We found significant HOA-related gender differences in Tcort, suggesting the involvement of female bone loss during and after menopause.

Erosive Hand Osteoarthritis: Recent Advances and Future Treatments.

PURPOSE OF THE REVIEW: Erosive hand osteoarthritis (EHOA) is an aggressive form of hand osteoarthritis that leads to significant disability, and recent data suggests that it is increasing in prevalence. This review provides an update of our current understanding of epidemiology, genetic associations, biomarkers, pathogenesis, and treatment of EHOA, with particular focus on studies published within the last 5 years. RECENT FINDINGS: New studies of EHOA have identified new genetic loci associated with disease, including variants in genes involved in inflammation and bone remodeling. Preclinical studies implicate pathways of innate immunity, including some that may be causal in the condition. Recent novel studies showed that inflammatory features identified by ultrasound and MRI are associated with development of erosive lesions over time on conventional radiography. In the future, these imaging modalities may be useful in identifying patients at risk of adverse outcomes. Promising new findings in genetics, biomarkers, and treatment targets will hopefully allow for future therapeutic options for this debilitating condition.

Association between radiographic hand osteoarthritis and bone microarchitecture in a population-based sample.

BACKGROUND: Subchondral bone plays an important role in the pathogenesis of radiographic osteoarthritis (OA). However, the bony changes that occur in hand OA (HOA) are much less understood. This study aimed to describe the association between radiographic HOA and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of the hand and radius in a population-based sample. METHODS: A total of 201 participants (mean age 72, 46% female) from the Tasmanian Older Adult Cohort (TASOAC) study underwent HRpQCT assessment of the 2nd distal and proximal interphalangeal (DIP, PIP), 1st carpometacarpal (CMC) joint, and distal radius. Radiographic HOA was assessed at the 2nd DIP, PIP joints, and the 1st CMC joint using the OARSI atlas. RESULTS: Proximal osteophyte and joint space narrowing (JSN) scores were consistently more strongly associated with HRpQCT measures compared to the distal site with positive associations for indices of bone size (total and trabecular bone area and cortical perimeter but inconsistent for cortical area) and negative associations for volumetric bone mineral density (vBMD). There was a decrease in trabecular number and bone volume fraction with increasing osteophyte and JSN score as well as an increase in trabecular separation and inhomogeneity. Osteophyte and JSN scores in the hand were not associated with HRpQCT measures at the distal radius. CONCLUSIONS: This hypothesis generating data suggests that bone size and trabecular disorganization increase with both osteophyte formation and JSN (proximal more than distal), while local vBMD decreases. This process appears to be primarily at the site of pathology rather than nearby unaffected bone.

Dorso-ventral osteophytes of interphalangeal joints correlate with cartilage damage and synovial inflammation in hand osteoarthritis: a histological/radiographical study.

OBJECTIVE: To detect dorsally located osteophytes (OP) on lateral x-ray views and to correlate their presence with the extent of structural joint damage, determined by histologic grading (cartilage damage and synovial inflammation) and radiographic scoring in hand osteoarthritis (HOA). METHODS: Distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints were obtained from post mortem specimens (n = 40). Multiplanar plain x-rays were taken (dorso/palmar (dp) and lateral views). Radiographic OA was determined by the Kellgren and Lawrence classification. Joint samples were prepared for histological analysis and cartilage damage was graded according to the Mankin scoring system. Inflammatory changes of the synovial membrane were scored using the general synovitis score (GSS). Spearman's correlation was applied to examine the relationship between histological and radiographical changes. Differences between groups were determined by Mann-Whitney test. RESULTS: Bony proliferations that were only detectable on lateral views but reminiscent of OPs on dp images were termed dorso-ventral osteophytes (dvOPs). All joints displaying dvOPs were classified as OA and the presence of dvOPs in DIP and PIP joints correlated with the extent of histological and radiographic joint damage, as well as with patient age. Joint damage in osteoarthritic DIP and PIP joints without any dvOPs was less severe compared to joints with dvOPs. Synovial inflammation was mainly present in joints displaying dvOPs and correlated with joint damage. CONCLUSION: dvOPs are associated with increasing structural alterations in DIP and PIP joints and can be seen as markers of advanced joint damage. Detecting dvOPs can facilitate the diagnosis process and improve damage estimation in HOA.

Common variants of RARRES2 and RETN contribute to susceptibility to hand osteoarthritis and related pain.

Aim: To examine the relationship of the RETN and RARRES2 genes with hand osteoarthritis (HOA) susceptibility risk, clinical severity and pain. Methods: A total of 3740 subjects comprising 1180 participants with HOA and 2560 controls were enrolled. Genetic association was evaluated at both single marker and haplotype levels using PLINK. Results: Two significant hits, single-nucleotide polymorphism (SNP) rs4721 from RARRES2 and SNP rs3745368 from RETN, were identified as being related to an increased risk of HOA. Significant associations were obtained for SNP rs3745368 with Kellgren-Lawrence grade in HOA patients and SNP rs4721 with pain analog scales of HOA patients. Conclusion: The authors' results indicate that RARRES2 and RETN affect HOA risk and are associated with clinical features and severity in patients with HOA.

Erosive hand osteoarthritis: latest findings and outlook.

Osteoarthritis (OA) most commonly affects knee joints, and the next most commonly affected sites are the hands and hips. Three distinct hand OA phenotypes have been described: erosive hand OA (EHOA), nodal hand OA - also known as non-erosive hand OA (non-EHOA) - and first carpometacarpal joint OA. EHOA predominantly affects women and is the most aggressive form of hand OA, characterized by a severe clinical onset and progression, leading to joint damage, disability and reduction of quality of life. Clinical signs of inflammation associated with EHOA include the acute onset of pain, swelling and redness. Moreover, EHOA is characterized by radiographic features such as central erosion, saw-tooth and gull-wing lesions and, rarely, ankylosis. The aim of this Review is to report the latest findings on epidemiology, clinical features, pathology and aetiopathogenesis, biomarkers, imaging modalities and treatments for EHOA. The ongoing development of new hand OA classification criteria should facilitate standardization between studies.

A novel fluorescence optical imaging scoring system for hand synovitis in rheumatoid arthritis-validity and agreement with ultrasound.

OBJECTIVES: To develop and validate a new semiquantitative fluorescence optical imaging (FOI) scoring system-the FOI Enhancement-Generated RA Score (FOIE-GRAS) for synovitis assessment in the hand. METHODS: The development of FOIE-GRAS was based on consensus of four experts in musculoskeletal imaging. Forty-six RA patients, eligible for treatment intensification and with ≥1 clinically swollen joints in the hands, and 11 healthy controls were included. FOI, ultrasound and clinical assessment of both hands were obtained at baseline and for RA patients after 3 and 6 months' follow-up. Twenty RA patients had an FOI rescan after 4 h. Synovitis was scored using FOIE-GRAS and the OMERACT ultrasound synovitis scoring system. All FOI images were scored by two readers. Inter-scan, inter- and intra-reader reliability were determined. Furthermore, FOIE-GRAS agreement with ultrasound and responsiveness was assessed. RESULTS: FOIE-GRAS synovitis was defined as early enhancement, and scores were based on the degree of coverage of the specific joint region after 3 s (0-3). Inter-scan, intra- and inter-reader intraclass correlations coefficients (ICC) were good to excellent for all baseline scores (0.76-0.98) and moderate to good for change (0.65-76).The FOIE-GRAS had moderate agreement with ultrasound (ICC 0.30-0.54) for total score, a good standardized response mean (>0.80), and moderate correlation with clinical joint assessment and DAS28-CRP. The median (interquartile range) reading time per FOI examination was 133 (109, 161) s. Scores were significantly lower in controls [1 (0, 4)] than RA patients [11 (6, 19)]. CONCLUSION: The FOIE-GRAS offers a feasible and reliable assessment of synovitis in RA, with a moderate correlation with ultrasound and DAS28-CRP, and good responsiveness.

Associations between fluorescence optical imaging and magnetic resonance imaging and symptoms in hand osteoarthritis.

OBJECTIVES: To investigate whether Fluorescence Optical Imaging (FOI) enhancement and MRI-defined synovitis are associated with pain and physical function in hand OA patients. METHODS: Bilateral FOI scans and MRI of the dominant hand were available for 221 patients. Finger joints were examined for tenderness on palpation. Pain in individual finger joints during the last 24 h and last 6 weeks and hand pain intensity by the Australian/Canadian hand index and Numeric Rating Scale were self-reported. On joint level, we applied logistic regression with generalized estimating equations to examine whether FOI enhancement and MRI-defined synovitis were associated with pain in the same joint. On subject level, we applied linear regression to assess whether FOI and MRI sum scores were associated with pain intensity and physical function. RESULTS: Metacarpophalangeal and thumb base joints were excluded from analyses due to little/no FOI enhancement. Finger joints with FOI enhancement on the composite image had higher odds (95% CI) of pain during the last 6 weeks [grade 1: 1.4 (1.2-1.6); grade 2-3: 2.1 (1.7-2.6)]. Similar results were found for joint pain during the last 24 h and joint tenderness in fingers. Numerically stronger associations were found between MRI-defined synovitis and finger joint pain/tenderness. FOI and MRI sum scores demonstrated no/weak associations with hand pain and physical function. CONCLUSION: FOI enhancement and MRI-defined synovitis were associated with pain in the same finger joint. None of the imaging modalities demonstrated consistent associations with pain, stiffness and physical function on subject level.

Elevated resting heart rate is associated with increased radiographic severity of knee but not hand joints.

Although the resting heart rate (RHR) predicts the clinical outcomes of cardiovascular disease, chronic obstructive lung disease, diabetes mellitus, and the risk of cancer, its role in patients with musculoskeletal diseases, such as osteoarthritis (OA), remains unclear. We explored the association of the RHR with the extents of radiographic changes in the knees and hands of 2369 subjects from the Dong-gu Study. The radiographic hand and knee joint findings were graded semi-quantitatively; we calculated total hand and knee joint scores. Multiple linear regression was performed to examine the associations between the RHR and the radiographic characteristics of these joints. For the knee joints, the RHR was associated positively with the total (p < 0.01), osteophyte (p < 0.01), joint space narrowing (JSN; p < 0.01), and tibial attrition (p = 0.02) scores after adjustment for age, sex, body mass index, smoking status, alcohol consumption, educational and physical activity levels, and comorbidities. For the hand joints, the RHR was associated positively with the JSN (p = 0.01) and subchondral cyst (p < 0.01) scores after such adjustment. The RHR was not associated with the total, osteophyte, sclerosis, erosion, or malalignment score for the hand joints. This study is the first to reveal an association between the RHR and the radiographic severity of knee, but not hand, OA.

Increased adiponectin levels are associated with higher radiographic scores in the knee joint, but not in the hand joint.

Several studies have evaluated the association between serum adiponectin levels and knee and hand osteoarthritis (OA); mixed results have been reported. We investigated the relationship between OA and serum adiponectin levels according to the radiographic features of knee and hand OA. A total of 2402 subjects was recruited from the Dong-gu Study. Baseline characteristics were collected via a questionnaire, and X-rays of knee and hand joints were scored using a semi-quantitative grading system. The relationship between serum adiponectin levels and radiographic severity was evaluated by linear and logistic regression analysis. Subjects in the higher serum adiponectin levels tertiles were older and had a lower body mass index (BMI) than those in the lower tertiles. Regarding knee joint scores, serum adiponectin levels was positively associated with the total (P < 0.001), osteophyte (P = 0.003), and joint space narrowing (JSN) scores (P < 0.001) after adjustment for age, sex, BMI, smoking, alcohol consumption, education, and physical activity. In terms of hand joint scores, no association was found between serum adiponectin levels and the total, osteophyte, JSN, subchondral cyst, sclerosis, erosion, or malalignment score after the above-mentioned adjustments. Similarly, subjects with serum adiponectin levels above the median had higher total radiographic scores in the knee joints, but not in the hand joints, after adjustment. An increased serum adiponectin levels was associated with a higher radiographic score in the knee joint, but not in the hand joint, suggesting the involvement of different pathophysiologic mechanisms in the development of OA between those joints.

Familial Clustering of Erosive Hand Osteoarthritis in a Large Statewide Cohort.

OBJECTIVE: Erosive hand osteoarthritis (OA) is a severe and rapidly progressing subset of hand OA. Its etiology remains largely unknown, which has hindered development of successful treatments. This study was undertaken to test the hypothesis that erosive hand OA demonstrates familial clustering in a large statewide population linked to genealogical records, and to determine the association of potential risk factors with erosive hand OA. METHODS: Patients diagnosed as having erosive hand OA were identified by searching 4,741,840 unique medical records from a comprehensive statewide database, the Utah Population Database (UPDB). Affected individuals were mapped to pedigrees to identify high-risk families with excess clustering of erosive hand OA as defined by a familial standardized incidence ratio (FSIR) of ≥2.0. The magnitude of familial risk of erosive hand OA in related individuals was calculated using Cox regression models. Association of potential erosive hand OA risk factors was analyzed using multivariate conditional logistic regression and logistic regression models. RESULTS: We identified 703 affected individuals linked to 240 unrelated high-risk pedigrees with excess clustering of erosive hand OA (FSIR ≥2.0, P < 0.05). The relative risk of developing erosive hand OA was significantly elevated in first-degree relatives (P < 0.001). There were significant associations between a diagnosis of erosive hand OA and age, sex, diabetes, and obesity (all P < 0.05). CONCLUSION: Familial clustering of erosive hand OA observed in a statewide database indicates a potential genetic contribution to the etiology of the disease. Age, sex, diabetes, and obesity are risk factors for erosive hand OA. Identification of causal gene variants in these high-risk families may provide insight into the genes and pathways that contribute to erosive hand OA onset and progression.

Seronegative Oligoarthritis Preceding Psoriasis by 9.5 Years.

We report a case of psoriatic arthritis where oligoarthritis preceded the skin lesions. A 57-year-old man complained of left third-finger pain. Laboratory examinations were negative for anti-cyclic citrullinated peptide antibodies and rheumatoid factor; he was treated for suspected rheumatoid arthritis. Six years later, X-ray revealed enthesitis of his fingers and wrist joint. At 9.5 years after the initial visit, skin lesions appeared in the left auricular region and buttock and dermatopathology findings indicated psoriasis vulgaris. The final diagnosis was psoriatic arthritis. In cases of seronegative oligoarthritis, psoriatic arthritis must be considered because some patients demonstrate osteoarticular lesions preceding skin lesions.

Need for Greater Attention to Joint Damage in Rhupus Patients: Results from an Ultrasound Study.

BACKGROUND The aim of this study was to evaluate the prevalence of inflammation and bone destruction of hand joints in rhupus patients through ultrasound examination. MATERIAL AND METHODS Ten rhupus patients and 33 systemic lupus erythematosus (SLE) patients with hand arthropathy were recruited in this single-center study, and the clinical features and ultrasound manifestations of these patients were analyzed. RESULTS We discovered that rhupus patients were older (47.31±4.35 years vs. 38.58±2.50 years, P=0.040), had longer duration of disease (median 72 months vs. median 12 months, P=0.040), had a higher positive rate (70% vs. 10.71%, P<0.001), and had higher titers of anti-CCP antibody (42.633±14.520 vs. 2.121±0.970, P<0.001) than SLE patients with arthropathy. More importantly, the prevalence rates of synovial hyperplasia (90% vs. 42.42%, P=0.008), synovitis (90% vs. 18.18%, P<0.001), synovial hyperplasia (70% vs. 10.71%, P<0.001), and bone destruction (70% vs. 6.06%, P<0.001) were higher in rhupus patients than in SLE patients with arthropathy. CONCLUSIONS Rhupus patients are more prone to develop synovitis, synovial hyperplasia, and bone destruction. Therefore, more attention should be paid to protection of the joints in rhupus patients.

Prevalence of subclinical synovitis of the hand in patients with systemic lupus erythematosus.

OBJECTIVES: To determine the prevalence of subclinical synovitis in Lupus patients without peripheral joint symptoms, in those with arthralgias without arthritis and those with episodic arthritis but without radiological structural damage. METHODS: We conducted a multicentre cross-sectional study. Patients with lupus from those three categories were recruited to take part in a greyscale ultrasound scan performed by an expert blinded rheumatologist. Data from a historical control group from a previous study was also included for comparisons. Images were assessed separately in order to determine the presence and level of synovitis following Eular recommendations. RESULTS: Ninety-six patients (88.5% female) with an average age of 40 ± 6.2 years old, were included. SLICC/ACR score was 0.6 ± 0.3 in the group without joint symptoms (group 0), 0.8 ± 0.3 in the group with arthralgias (group I) and 1.1 ± 0.4 in the group with episodic arthritis. The global prevalence of subclinical synovitis was 38.5%. In group 0, that prevalence was 30%. The time since onset of symptoms of patients with subclinical synovitis was longer than the rest of the patients (9.4 ± 2.2 vs 6.5 ± 4.0 years, P < 0.001). No other remarkable association was founded with clinical features of the disease. CONCLUSIONS: This is the first study focused on subclinical synovitis in patients with lupus. Other previous studies had included patients with different levels of arthropathy. Subclinical synovitis does exist in lupus patients in over a third of patients. Its meaning remains unclear and must be a topic of further studies.

Assessment of structural lesions, synovitis and bone marrow lesions in erosive hand osteoarthritis on MRI (0.3T) compared to the radiographic anatomical Verbruggen-Veys score.

OBJECTIVE: To evaluate prevalence of structural lesions, synovitis and bone marrow lesions (BMLs) on MRI performed with a 0.3T imaging system in patients with erosive hand osteoarthritis (EHOA) and to compare them to the anatomic radiographic Verbruggen-Veys score (VV). DESIGN: For this Cross-sectional study, fifty-five EHOA patients were studied with 0.3T contrast-enhanced MRI and radiography (RX) of their dominant hand. Structural lesions were scored according to the OMERACT Hand Osteoarthritis MRI Scoring System as follows: osteophytes and erosions were graded from 0 to 3. On joint destruction lesion synovitis and BMLs were graded from 0 to 1. And on MRI, we evaluated the presence of several structural features: N: normal, O: osteophytic lesions, E: erosive lesions, E/O: osteophytic and erosive lesions and D: joint destruction. RX was scored according to the VV system. Relations between MRI features and VV stages were analysed. RESULTS: MRI identified more structural lesions than RX (77.3% versus 74.8%) and particularly more erosive lesions (E or E/O) than VV Phase E (33.5% versus 20.2%). E/O and D were mostly found on MRI. Synovitis and BMLs were significantly associated with E/O and D with the following odds ratios (ORs): 8.4 (95% CI 1.8-13.6); OR: 13.7 (95% CI 2.9-21.0); OR: 15.7 (95% CI 3.2-23.5); OR: 38.5 (95% CI 9.5-57.0), respectively. CONCLUSION: MRI 0.3T appears completely relevant for EHOA lesion analysis. First, MRI shows more erosive lesions than RX in EHOA; second, it allows for the analysis of synovitis and BMLs to be associated with more specific structural MRI features (E/O and D).