Scoring inflammatory activity of the spine by magnetic resonance imaging in ankylosing spondylitis: a multireader experiment

OBJECTIVE: Magnetic resonance imaging (MRI) of the spine is increasingly important in the assessment of inflammatory activity in clinical trials with patients with ankylosing spondylitis (AS). We investigated feasibility, inter-reader reliability, sensitivity to change, and discriminatory ability of 3 different scoring methods for MRI activity and change in activity of the spine in patients with AS. METHODS: Thirty sets of spinal MRI at baseline and after 24 weeks of followup, derived from a randomized clinical trial comparing a tumor necrosis factor (TNF)-blocking drug (n = 20) with placebo (n = 10) and selected to cover a wide range of activity at baseline and change in activity, were presented electronically in a partial latin-square design to 9 experienced readers from different countries (Europe, Canada). Readers scored each set of MRI 3 times, using 3 different methods including the Ankylosing Spondylitis spine Magnetic Resonance Imaging-activity [ASspiMRI-a, grading activity (0-6) per vertebral unit in 23 units]; the Berlin modification of the ASspiMRI-a; and the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system, which scores the 6 vertebral units considered by the reader as the most abnormal, with additional scores for "depth" and "intensity." Both the order of the methods used by each reader and the timepoints (before/after treatment) were randomized. Feasibility of each scoring system was evaluated by measuring the mean time needed to score each set of MRI, and inter-reader reliability was evaluated by smallest detectable change (SDC) and by intraclass correlation coefficients (ICC) for all readers together and for all possible reader pairs separately. Sensitivity to change was investigated by calculating Guyatt's effect size on change scores. Discriminatory ability was assessed using Z-scores (Mann-Whitney test) comparing change in score between patients treated with TNF-blocking drug and placebo. RESULTS: The mean time to score one set of MRI was shortest for the Berlin method. SDC was lowest for the Berlin method and highest for SPARCC. Overall inter-reader ICC per method were between 0.49 and 0.77 for scoring activity status, and between 0.46 and 0.72 for scoring activity change. ICC for all possible reader pairs showed much more fluctuation per method, with lowest observed values of about 0.05 (very low agreement) and highest observed values over 0.90 (excellent agreement). In general, ICC for SPARCC were consistently higher than for other systems. Sensitivity to change differed per reader, and was more consistent with SPARCC than with the other methods, but was in general excellent for all 3 methods. Discrimination between groups (TNF-blocker vs placebo) assessed by Z-scores was good and comparable among methods. CONCLUSION: This experiment demonstrates the feasibility of multiple-reader MRI scoring exercises for method comparison, provides evidence for the feasibility, reliability, sensitivity to change, and discriminatory capacity of all 3 tested scoring systems to be used in assessing spinal activity on MRI in patients with AS in clinical trials. On the basis of these results it is not possible to prioritize one of the 3 methods.     

Training and calibration improve inter-reader reliability of joint damage assessment using magnetic resonance image scoring and computerized erosion volume measurement

OBJECTIVE: To assess the inter-reader reliability of 3 rheumatologist readers before and after training using 2 methods of assessment: magnetic resonance imaging (MRI) computerized erosion volume assessment and MRI scoring using the OMERACT-5 Rheumatoid Arthritis MRI Score (OM-5 RAMRIS) criteria. METHODS: Erosion volumes were measured in 10 patients [5 wrist and 5 metacarpophalangeal (MCP) joint studies] with rheumatoid arthritis. Erosion scores were derived from this group and 8 additional subjects to provide a total of 18 subjects (10 wrist and 8 MCP joint studies) with MRI scores for comparison. Subjects were selected from existing MRI databases to provide a spectrum of joint damage for assessment. Initial reading was undertaken after the 2 inexperienced readers were provided with instructions regarding OSIRIS computer software and definitions of the OMERACT score; no other formal training was undertaken. One month after the initial reading, the 2 inexperienced readers undertook a 3 hour training session and all 3 readers then took part in 2 subsequent 2 hour calibration sessions. Each reader then reread the original MRI studies using the computerized erosion volume method and the OMERACT MRI RA score. The interval between the baseline and post-training reading was 2 months. All reading was undertaken on a computer workstation and readers were blinded to other readers' results. RESULTS: For the wrist MRI studies, inter-reader agreement improved considerably after training for both the computerized MRI volume method and the OMERACT MRI score [intraclass correlation coefficients (ICC) 0.21 and 0.46, respectively, pre-training; 0.92 and 0.85 post-training]. The correlation between all readers' scores and volumes was excellent at baseline and post-training. For the MCP joint studies, inter-reader agreement was moderate at baseline for the erosion volume and score (ICC 0.51 and 0.61). While there was some improvement in agreement post-training for the scoring method (ICC 0.75), there was no significant improvement for the erosion volumes (ICC 0.58). CONCLUSION: Overall, inter-reader agreement for erosion scoring and volume measurement was higher for the wrist joint. The lack of improvement in the MCP joint region for the erosion volume measurements appears to relate primarily to difficulties in estimating the erosion border in the proximal MCP joints using the manual outlining tool. This limits the usefulness of erosion volume measurements in this joint region.     

OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 5: an international multicenter reliability study using computerized MRI erosion volume measurements

Scoring erosions on magnetic resonance imaging (MRI) is one method of estimating damage in patients with rheumatoid arthritis (RA), but it has limitations. The aim of this pilot study was to assess the feasibility and inter-reader reliability of computer assisted erosion volume estimation in patients with RA. Intra-reader and inter-occasion reliability was also assessed, and different slice thicknesses were compared in terms of erosion volume estimation. A 3 mm slice thickness 3D gradient-echo sequence followed by a 1 mm sequence was performed at baseline and repeated within 24 h with metacarpophalangeal (MCP) joints 2 to 5 of the dominant hand included in the field of view. Three readers were instructed to grade MCP 2 and 3 using the OMERACT grading system and then to measure the erosion volume of the same joints using OSIRIS software. The inter-reader reliability of the grading method and the volume method was calculated, as well as the inter-occasion reliability, by comparing results from each reader from baseline to the followup scan. One reader performed repeat volume measurements on 5 patients to assess the intra-reader reliability. Five patients were included in the study. Expressed in terms of intraclass correlation coefficients (ICC), the inter-reader and inter-occasion reliability of the volume method were comparable to the existing OMERACT scoring system, but large systematic differences in volume estimations were found between readers. The intra-reader reliability was excellent. Good correlation was demonstrated between the total erosion scores and the total erosion volumes. For both erosion volumes and erosion scores, 1 mm and 3 mm acquisitions produced variable results between readers, with no clear pattern of underestimation or overestimation for either slice thickness. The volume estimation method was more time consuming, taking roughly 5 times as long as the scoring method. Computerized MRI erosion volume measurements are feasible, with high intra-observer and inter-occasion reliabilities. Despite high ICC, the inter-observer reliability is not sufficient for multicenter use without prior reader training and calibration. The optimal slice thickness was not determined.     

Validation of whole‐body against conventional magnetic resonance imaging for scoring acute inflammatory lesions in the sacroiliac joints of patients with spondylarthritis

Objective

To compare the performance of whole‐body magnetic resonance imaging (MRI) versus conventional MRI in assessing acute inflammatory lesions of the sacroiliac (SI) joints in patients with established and active spondylarthritis (SpA) using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. This study is validating whole‐body MRI against the current MRI standard for assessing active inflammatory lesions of the SI joints in patients with SpA.

Methods

Thirty‐two SpA patients with clinically active disease (Bath Ankylosing Spondylitis Disease Activity Index score ≥4) fulfilling the modified New York criteria were scanned by whole‐body and conventional MRI of the SI joints. The MRIs were scored independently in random order by 3 readers blinded to patient identity. Active inflammatory lesions of the SI joints were recorded on a Web‐based SPARCC index. Pearson's correlation coefficients were used to compare scores for whole‐body and conventional MRI for each reader, whereas intraclass correlation coefficients (ICCs) were used to compare interobserver reliability.

Results

The Pearson's correlation coefficients between whole‐body and conventional MRI per rater were 0.94, 0.87, and 0.93. The mean sum scores for conventional versus whole‐body MRI were statistically significantly higher for all 3 readers, although all patients showing inflammatory lesions on conventional MRI also demonstrated them on whole‐body MRI. The ICCs(2,1) were 0.69, 0.78, and 0.95 for conventional MRI, and 0.79, 0.85, and 0.96 for whole‐body MRI for the 3 possible reader pairs.

Conclusion

Whole‐body and conventional MRI scores show a strong correlation and comparable reliability for the detection of inflammatory lesions of the SI joints.     

Is there a preferred method for scoring activity of the spine by magnetic resonance imaging in ankylosing spondylitis?

This report summarizes the discussion during a module update at OMERACT 8 on scoring methods for activity in the spine on magnetic resonance imaging. The conclusion was that the 3 available scoring methods are all very good with respect to discrimination and feasibility: the Ankylosing Spondylitis spine MRI score for activity (ASspiMRI-a), the Berlin method (a modification of the ASspiMRI-a), and the Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Index for Assessment of Spinal Inflammation in AS (SPARCC). All 3 methods were judged to be similar with respect to responsiveness and discrimination, although the differences in between-reader intraclass correlation coefficients (ICC) were judged to be relevant (the SPARCC method provided consistently higher ICC). The Berlin and SPARCC methods were preferred most frequently. The development of a new method combining the best elements of all methods is an additional possibility.     

Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study

OBJECTIVES: To describe a novel scoring system for the assessment of tenosynovitis by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis, and assess its intra- and inter-reader reliability in a multireader, longitudinal setting. METHODS: Flexor and extensor tenosynovitis were evaluated at the level of the wrist in 10 different anatomical areas, graded semi-quantitatively from grade 0 to 3 (total score 0-30), based on the maximum width of post-contrast enhancement within each anatomical area on axial T1-weighted MR images. Ten sets of baseline and 1-year follow-up MR images of the wrists of patients with rheumatoid arthritis with early and established disease were scored independently by four readers twice on 2 consecutive days. Intra- and inter-reader agreements were evaluated. RESULTS: The intrareader intraclass correlation coefficients (ICCs) were high for status scores (median ICCs 0.84-0.88) and slightly lower for change score (0.74). The smallest detectable difference (SDD) in % of the maximum score was 11.2-11.5% for status scores and 13.3% for change scores. Inter-reader single-measure ICCs were acceptable for both status scores (median 0.73-0.74) and change scores (0.67), while average-measures ICCs were very high for both status and change score (all > or =0.94). The median scoring time per patient (baseline and follow-up images) was 7 min (range 3-10). CONCLUSIONS: The introduced tenosynovitis scoring system demonstrates a high degree of multireader reliability, is feasible, and may be used as an adjuvant to the existing OMERACT RAMRIS score, allowing improved quantification of inflammatory soft tissue changes in patients with rheumatoid arthritis.     

Validation of the spondyloarthritis research consortium of Canada magnetic resonance imaging spinal inflammation index: is it necessary to score the entire spine?

OBJECTIVE: The Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) spinal inflammation index has been developed to objectively measure inflammation in ankylosing spondylitis (AS) and to assess change in response to therapeutic intervention. Scoring of the entire spine limits feasibility and a scoring method that records inflammation in only the more severely affected spinal segments may improve feasibility without sacrificing performance. METHODS: MRI films of 68 patients with AS were assessed in random order by 2 blinded readers. Interreader reliability was assessed by intraclass correlation coefficient. Pre- and posttreatment MRI films of 29 patients randomized to placebo or anti-tumor necrosis factor alpha (anti-TNFalpha) therapy were read by readers blinded to chronology, and responsiveness was assessed by effect size and standardized response mean. The performance of scores based on 6, 8, 10, and all 23 spinal discovertebral units (DVU) was compared. RESULTS: The median number of affected spinal levels per patient was 6.0 and 62% of all affected levels were included when analysis was limited to only the 6 most severely affected levels per patient. Comparison of DVU scores that were limited to only the more severely affected DVU (6-, 8-, 10-DVU score) with scores for all 23 spinal DVU showed excellent interreader reliability for status and change scores (Spearman's correlation >0.90) as well as similar construct validity. Responsiveness to anti-TNFalpha therapy was greater when the more limited scoring methods were used and was greatest with the 6-DVU score. CONCLUSION: The SPARCC MRI spinal inflammation index performs better when analysis is limited to a maximum of 6 most severely affected levels compared with assessment of the entire spine. This should improve its feasibility in clinical trials and research.     

OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 3: an international multicenter reliability study using the RA-MRI Score

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.     

Validation of the Spondyloarthritis Research Consortium of Canada magnetic resonance imaging spinal inflammation index: Is it necessary to score the entire spine?

Objective

The Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) spinal inflammation index has been developed to objectively measure inflammation in ankylosing spondylitis (AS) and to assess change in response to therapeutic intervention. Scoring of the entire spine limits feasibility and a scoring method that records inflammation in only the more severely affected spinal segments may improve feasibility without sacrificing performance.

Methods

MRI films of 68 patients with AS were assessed in random order by 2 blinded readers. Interreader reliability was assessed by intraclass correlation coefficient. Pre‐ and posttreatment MRI films of 29 patients randomized to placebo or anti–tumor necrosis factor α (anti‐TNFα) therapy were read by readers blinded to chronology, and responsiveness was assessed by effect size and standardized response mean. The performance of scores based on 6, 8, 10, and all 23 spinal discovertebral units (DVU) was compared.

Results

The median number of affected spinal levels per patient was 6.0 and 62% of all affected levels were included when analysis was limited to only the 6 most severely affected levels per patient. Comparison of DVU scores that were limited to only the more severely affected DVU (6‐, 8‐, 10‐DVU score) with scores for all 23 spinal DVU showed excellent interreader reliability for status and change scores (Spearman's correlation >0.90) as well as similar construct validity. Responsiveness to anti‐TNFα therapy was greater when the more limited scoring methods were used and was greatest with the 6‐DVU score.

Conclusion

The SPARCC MRI spinal inflammation index performs better when analysis is limited to a maximum of 6 most severely affected levels compared with assessment of the entire spine. This should improve its feasibility in clinical trials and research.

     

Radiological scoring methods in ankylosing spondylitis. Reliability and change over 1 and 2 years

OBJECTIVE: To compare reliability and change over time of radiological scoring methods in ankylosing spondylitis (AS). METHODS: Two trained observers scored 217 sets of radiographs from baseline and from one and 2 years' followup. Sacroiliac (SI) joints were grade 0-4 by the New York method and Stoke Ankylosing Spondylitis Spine Score (SASSS). Hips and cervical and lumbar spine were graded 0-4 by Bath Ankylosing Spondylitis Radiology Index (BASRI). BASRI spinal scores and New York SI are combined into BASRI-spine (score 2-12) and with the addition of BASRI-hips into BASRI-total (2-16). Cervical and lumbar spine were also scored in detail (SASSS, 0-36 each) and were combined into SASSS-total or "modified" SASSS (both range 0-72). To assess change a smallest detectable difference (SDD) was estimated for data on a quasi-interval scale. RESULTS: The SI scoring methods showed intra and interobserver kappa between 0.36 and 0.70. The BASRI-hip reached kappa between 0.59 and 0.84. Combined SASSS scores were most reliable, with intra and interobserver intraclass correlation coefficients (ICC) between 0.90 and 0.96. The ICC of the combined BASRI scores were also very good, ranging from 0.85 to 0.95. For SI New York, SI SASSS, and BASRI-hip, 0.3-1.2% of patients deteriorated 1 grade; 7.5% deteriorated 1 grade (6.3% of maximum score) in BASRI-spine and BASRI-total, and observers agreed in up to 48% of the cases that no change occurred. The SDD was lowest (7.5; 10% of maximum score) for "modified" SASSS. Only 0.8% of patients deteriorated more than the SDD and observers agreed in up to 92% of the cases that no change occurred. CONCLUSION: Radiological scoring methods for AS are moderately to excellently reliable. Under the selected scoring conditions (concealed time order, average of 2 observers, SDD based on interobserver data, unselected patient population) there was too little change over 2 years to be detected reliably by the scoring methods.     

OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 4: an international multicenter longitudinal study using the RA-MRI Score

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.     

Spondyloarthritis research Consortium of Canada magnetic resonance imaging index for assessment of sacroiliac joint inflammation in ankylosing spondylitis

OBJECTIVE: To develop a feasible magnetic resonance imaging (MRI)-based scoring system for sacroiliac joint inflammation in patients with ankylosing spondylitis (AS) that requires minimal scan time, does not require contrast enhancement, evaluates lesions separately at each articular surface, and limits the number of sacroiliac images that are scored. METHODS: A scoring method based on the assessment of increased signal denoting bone marrow edema on T2-weighted STIR sequences was used. MRI films were assessed blindly in random order at 2 sites by multiple readers. Intra- and interreader reliability was assessed by intraclass correlation coefficient (ICC); the 24-week response of patients with AS randomized to placebo:infliximab (3:8) was assessed by effect size and standardized response mean. The reliability and responsiveness of the scoring method were compared for STIR and gadolinium diethylenetriaminepentaacetic (Gd-DTPA)-enhanced MRI sequences. RESULTS: We scanned 11 patients with AS with clinically active disease and 11 additional patients randomized to the trial of infliximab therapy. ICC for total sacroiliac joint STIR score ranged from 0.90 to 0.98 (P < 0.00001) and interobserver ICC for combined readers from the 2 sites was 0.84 (P < 0.0001). ICC for change scores was lower for STIR (ICC 0.53) than for Gd-DTPA-enhanced sequences (ICC 0.79). Responsiveness was poor, although fusion was evident in one-third of patients who received treatment (placebo:infliximab) and inflammation scores were low. CONCLUSION: The Spondyloarthritis Research Consortium of Canada MRI index is a feasible and reproducible index for measuring sacroiliac joint inflammation in patients with AS.     

Reproducibility and sensitivity to change of four scoring methods for the radiological assessment of osteoarthritis of the hand

BACKGROUND: Osteoarthritis (OA) of the hand could be a relevant model to study the progression of OA in structure-modification trials. Various methods are proposed to assess hand OA and its progression radiologically. OBJECTIVE: To compare intra-reader and inter-reader precision and sensitivity to change of four radiological scoring methods proposed in hand OA. METHODS: 2 trained readers scored separately 105 pairs of radiographs (baseline; year 1), selected from patients enrolled in a randomised controlled trial, for inter-reader reliability and sensitivity to change. They scored twice 60 pairs among the 105 for cross-sectional and longitudinal intra-reader reliability. Radiological hand OA assessment used: global, Kellgren-Lawrence (KL), Kallman and Verbruggen scoring methods. Inter- and intra-reader reliabilities were studied using intraclass coefficient (ICC) and the Bland-Altman method. Sensitivity to change was compared by calculating the standardised response means. RESULTS: Transversal intra-reader reproducibility ICCs ranged from 0.922 to 0.999. Verbruggen ranked the highest, followed by the KL and Kallman methods. Inter-rater reliability was higher for the Verbruggen scores, followed by the KL, global and Kallman scores (ICC 0.706-0.999). Longitudinal intra-reader reliability (baseline; year 1) was better using the Kallman and KL (ICC 0.986 and 0.990), followed by the Verbruggen (0.941) or global methods (0.939). Standardised response means ranged from 0.24 (KL) to 0.29 (Kallman). CONCLUSION: All four methods compared well with respect to reliabilities. However, the Verbruggen and Kallman methods performed better. The method most sensitive to change was the Kallman method, followed by Verbruggen and global scores. This study also suggests that structural changes could be detected in hand OA over a 1-year period.     

Imagent improves endocardial border delineation,inter-reader agreement,and the accuracy of segmental wall motion assessment

BACKGROUND: This study was conducted to assess the ability of a new echocardiographic contrast agent, Imagent (perflexane lipid microspheres; Alliance Pharmaceutical Corp., San Diego, CA), to improve endocardial border delineation (EBD) and assessment of segmental wall motion (SWM). This was achieved by analysis of inter-reader agreement by echocardiography and comparison with an independent imaging technique, magnetic resonance imaging (MRI). METHODS: Two separate, independent, prospective, randomized, controlled, multicenter trials were conducted at 26 centers and included a total of 409 efficacy-evaluable patients. In Study A 206 patients were randomized to receive either Imagent or saline and in Study B, 203 patients received Imagent with a subset imaged by both echocardiography and MRI. All patients were required to have suboptimal baseline images using fundamental imaging. Images were optimized at baseline prior to contrast and the settings maintained post-contrast. Imagent, a suspension of perfluorohexane-filled spheres with flexible lipid shells, was administered as an IV bolus at 0.125 mg/kg body weight. Gated MRI studies were performed within 48 hours of dosing in a subset of 26 subjects. Six expert independent blinded readers reviewed unpaired noncontrast and contrast exams and scored EBD and SWM. Analysis of inter-reader agreement was performed by comparing the SWM score (1 to 5) recorded by each reader pair. In addition, unanimity between readers for SWM was evaluated. For comparison to MRI, the results from echo readers 4, 5, and 6 were each compared with a single independent MRI reader. RESULTS: The patients enrolled in these clinical trials displayed markedly suboptimal images with 49% and 71% (Study A and Study B) of the segments determined by the readers to be suboptimal prior to contrast administration. All readers recorded statistically significant (P < 0.0001) improvement in total EBD scores following the administration of Imagent. Comparison of noncontrast SWM scores for each pair of echo readers resulted in agreement in an average of 39%, of segments in Study A, and 31% of the segments in Study B. Use of Imagent improved agreement in SWM scores to 65% in Study A, and 48% of segments in Study B (P < 0.0001) for all reader pairs in both studies. Reader unanimity in SWM scores increased from 13% to 41% of the segments with the administration of Imagent. Blinded review of the noncontrast echo examinations resulted in agreement with MRI derived SWM scores in 15% of the segments. The administration of Imagent improved this agreement to 47%, of the segments (P < pr = 0.0005 for each blinded reader). CONCLUSIONS: Use of Imagent during echocardiographic imaging improves EBD, providing a significant improvement in inter-reader agreement in SWM evaluation with echo and greater than a threefold improvement in SWM scoring accuracy with MRI.     

Imaging Findings Suggestive of Axial Spondyloarthritis in Diffuse Idiopathic Skeletal Hyperostosis

Objective

To describe the magnetic resonance imaging (MRI) findings in diffuse idiopathic skeletal hyperostosis (DISH) patients and to assess the proportion of DISH patients whose MRI findings would fulfill the Assessment of Spondyloarthritis International Society (ASAS) criteria for a positive MRI of axial spondyloarthritis (SpA).

Methods

This study involved all DISH patients who had a spine or sacroiliac (SI) joint MRI performed between January 2009 and December 2014. Sociodemographic and clinical data were collected. Available radiographs and MRI were analyzed and blindly scored by an experienced reader, using the Spondyloarthritis Research Consortium of Canada (SPARCC) scores for both spine and SI joint MRI.

Results

A total of 53 symptomatic DISH patients was included in the analysis. The mean ± SD SPARCC score of the spine was 18.3 ± 23.4. Thirty‐five patients (67.3%) had at least 1 fatty corner. Thirty patients (57.7%) met the ASAS definition of a spine MRI suggestive of axial SpA, but only 6 patients (15.8%) with an available SI joint MRI had sacroiliitis according to ASAS criteria. Only 1 patient (3.3%) had ≥3 erosions on the SI joint.

Conclusion

Inflammatory lesions of the spine are common on the MRI of symptomatic DISH patients, and more than half fulfilled the ASAS criteria for a spine MRI suggestive of axial SpA. However, only a few patients met the ASAS definition of active sacroiliitis, suggesting that MRI of the SI joint but not of the spine might allow the differential diagnosis of DISH versus axial SpA in the elderly.     

Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study

OBJECTIVE: To compare the efficacy of adalimumab versus placebo in reducing spinal and sacroiliac (SI) joint inflammation, by magnetic resonance imaging (MRI) in patients with active ankylosing spondylitis (AS). METHODS: This was a randomized, multicenter, double-blind, placebo-controlled study. Patients (n = 82) received 40 mg adalimumab or placebo every other week during an initial 24-week double-blind period. MRIs of both the spine and SI joints were obtained at baseline, week 12, and week 52. Spinal and SI joint inflammation were measured using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. RESULTS: The spine SPARCC score in placebo-treated patients increased by a mean of 9.4% from baseline, compared with a mean decrease of 53.6% in adalimumab-treated patients (P < 0.001); the SI joint SPARCC score decreased by a mean of 12.7% from baseline in placebo-treated patients and by 52.9% in adalimumab-treated patients (P = 0.017). The response in adalimumab-treated patients was maintained at week 52. Placebo-treated patients were switched to open-label adalimumab treatment at week 24 and experienced similar reductions in spinal and SI joint inflammation by week 52. Similar large reductions in the spine and SI joint SPARCC scores were noted, even in patients who failed to meet the ASsessment in Ankylosing Spondylitis (International Working Group) criteria (nonresponders) at 12 weeks. In adalimumab-treated patients, a reduced C-reactive protein concentration at week 12 was significantly associated with improvement in the spine SPARCC score (P = 0.018). CONCLUSION: Adalimumab significantly reduced both spinal and SI joint inflammation in patients with active AS after 12 weeks of treatment, and these improvements were maintained for up to 52 weeks.     

What is the most appropriate radiologic scoring method for ankylosing spondylitis? A comparison of the available methods based on the Outcome Measures in Rheumatology Clinical Trials filter

OBJECTIVE: To select the most appropriate radiologic scoring method for the evaluation of radiographic progression in ankylosing spondylitis (AS) in clinical trials. METHODS: The validity of the currently available methods, the Bath Ankylosing Spondylitis Radiology Index (BASRI), the Stoke Ankylosing Spondylitis Spine Score (SASSS), and the modified SASSS (M-SASSS), was tested according to the aspects of the Outcome Measures in Rheumatology Clinical Trials filter: truth, discrimination (reliability and sensitivity to change), and feasibility, using radiographs of 133 patients at 4 different time points (baseline, 1 year, 2 years, and 4 years). One observer scored these sets in chronological order. To assess interobserver reliability, a second observer scored radiographs of 20 patients at the 4 different time points. RESULTS: After 4 years, 9% and 8% of patients showed changes >0 in the sacroiliac (SI) joints and hips, respectively. Independent of the method chosen, approximately 40% of patients showed changes in both the lumbar and cervical spine. Therefore, it was concluded that, for the assessment of progression, SI joints and hips are of minor importance. The intraclass correlation coefficient (ICC) varied from 0.87 to 0.98 and ICCs for intraobserver scores varied from 0.96 to 0.99. Concerning progression scores, only the ICC for the M-SASSS measured after 2 years remained acceptable (0.82). The intraobserver scores for progression after 2 years of followup were an ICC of 0.93 for the BASRI, an ICC of 0.79 for the SASSS, and an ICC of 0.95 for the M-SASSS. Concerning sensitivity to change, it was found that the M-SASSS classified the highest percentage of patients with a change >0. CONCLUSION: The M-SASSS is the most appropriate method by which to score the radiographic progression in AS patients in clinical trials.     

Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: A multicenter,randomized, double‐blind,placebo‐controlled study

Objective

To compare the efficacy of adalimumab versus placebo in reducing spinal and sacroiliac (SI) joint inflammation, by magnetic resonance imaging (MRI) in patients with active ankylosing spondylitis (AS).

Methods

This was a randomized, multicenter, double‐blind, placebo‐controlled study. Patients (n = 82) received 40 mg adalimumab or placebo every other week during an initial 24‐week double‐blind period. MRIs of both the spine and SI joints were obtained at baseline, week 12, and week 52. Spinal and SI joint inflammation were measured using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index.

Results

The spine SPARCC score in placebo‐treated patients increased by a mean of 9.4% from baseline, compared with a mean decrease of 53.6% in adalimumab‐treated patients (P < 0.001); the SI joint SPARCC score decreased by a mean of 12.7% from baseline in placebo‐treated patients and by 52.9% in adalimumab‐treated patients (P = 0.017). The response in adalimumab‐treated patients was maintained at week 52. Placebo‐treated patients were switched to open‐label adalimumab treatment at week 24 and experienced similar reductions in spinal and SI joint inflammation by week 52. Similar large reductions in the spine and SI joint SPARCC scores were noted, even in patients who failed to meet the ASsessment in Ankylosing Spondylitis (International Working Group) criteria (nonresponders) at 12 weeks. In adalimumab‐treated patients, a reduced C‐reactive protein concentration at week 12 was significantly associated with improvement in the spine SPARCC score (P = 0.018).

Conclusion

Adalimumab significantly reduced both spinal and SI joint inflammation in patients with active AS after 12 weeks of treatment, and these improvements were maintained for up to 52 weeks.

     

OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Summary of OMERACT 6 MR Imaging Module

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.     

Hounsfield Units measured in low dose CT reliably assess vertebral trabecular bone density changes over two years in axial spondyloarthritis

ObjectivesTo describe low dose Computed Tomography (ldCT) Hounsfield Units (HU) two-year change-from-baseline values (expressing trabecular bone density changes) and analyse their inter-reader reliability per vertebra in radiographic axial spondyloarthritis (r-axSpA).MethodsWe used 49 patients with r-axSpA from the multicentre two-year Sensitive Imaging in Ankylosing Spondylitis (SIAS) study. LdCT HU were independently measured by two trained readers at baseline and two years. Mean (standard deviation, SD) for the change-from-baseline HU values were provided per vertebra by reader. Intraclass correlation coefficients (ICC; absolute agreement, two-way random effect), Bland-Altman plots and smallest detectable change (SDC) were obtained. Percentages of vertebrae in which readers agreed on the direction of change and on change >|SDC| were computed.ResultsOverall, 1,053 (98% of all possible) vertebrae were assessed by each reader both at baseline and two years. Over two years, HU mean change values varied from -23 to 28 and 29 for reader 1 and 2, respectively. Inter-reader reliability of the two-year change-from-baseline values per vertebra was excellent: ICC:0.91-0.99; SDC:6-10; Bland-Altman plots were homoscedastic, with negligible systematic error between readers. Readers agreed on the direction of change in 88-96% and on change >|SDC| in 58-94% of vertebrae, per vertebral level, from C3 to L5. Overall, similar results were obtained across all vertebrae.ConclusionLdCT measurement of HU is a reliable method to assess two-year changes in trabecular bone density at each vertebra from C3-L5. Being reliable across all vertebrae, this methodology can aid the study of trabecular bone density changes over time in r-axSpA, a disease affecting the whole spine.