Detection of structural lesions of the sacroiliac joints in patients with spondyloarthritis: A comparison of T1-weighted 3D spoiled gradient echo MRI and MRI-based synthetic CT versus T1-weighted turbo spin echo MRI.

OBJECTIVES: To investigate the detection of erosion, sclerosis and ankylosis using 1 mm 3D T1-weighted spoiled gradient echo (T1w-GRE) MRI and 1 mm MRI-based synthetic CT (sCT), compared with conventional 4 mm T1w-TSE. MATERIALS AND METHODS: Prospective, cross-sectional study. Semi-coronal 4 mm T1w-TSE and axial T1w-GRE with 1.6 mm slice thickness and 0.8 mm spacing between overlapping slices were performed. The T1w-GRE images were processed into sCT images using a commercial deep learning algorithm, BoneMRI. Both were reconstructed into 1 mm semi-coronal images. T1w-TSE, T1w-GRE and sCT images were assessed independently by 3 expert and 4 non-expert readers for erosion, sclerosis and ankylosis. Cohen's kappa for inter-reader agreement, exact McNemar test for lesion frequencies and Wilcoxon signed-rank test for confidence in lesion detection were used. RESULTS: Nineteen patients with axial spondyloarthritis were evaluated. T1w-GRE increased inter-reader agreement for detecting erosion (kappa 0.42 vs 0.21 in non-experts), increased detection of erosion (57 vs 43 of 152 joint quadrants) and sclerosis (26 vs 17 of 152 joint quadrants) among experts, and increased reader confidence for scoring erosion and sclerosis. sCT increased inter-reader agreement for detecting sclerosis (kappa 0.69 vs 0.37 in experts) and ankylosis (0.71 vs 0.52 in non-experts), increased detection of sclerosis (34 vs 17 of 152 joint quadrants) and ankylosis (20 vs 13 of 76 joint halves) among experts, and increased reader confidence for scoring erosion, sclerosis and ankylosis. CONCLUSION: T1w-GRE and sCT increase sensitivity and reader confidence for the detection of erosion, sclerosis and ankylosis, compared with T1w-TSE. CLINICAL RELEVANCE STATEMENT: These methods improve the detection of sacroiliac joint structural lesions and might be a useful addition to SIJ MRI protocols both in routine clinical care and as structural outcome measures in clinical trials.

Quantification of cross-vendor variation in ADC measurements in vendor-specific prostate MRI-protocols.

PURPOSE: The purpose of this study was to quantify the variability of Apparent Diffusion Coefficient (ADC) and test if there were statistically significant differences in ADC between MRI systems and sequences. METHOD: With a two-chamber cylindrical ADC phantom with fixed ADC values (1,000 and 1,600x10-6 mm2/s) a single-shot (ss) Echo Planar Imaging (EPI), a multi-shot EPI, a reduced field of view DWI (zoom) and a Turbo Spin Echo DWI sequence were tested in six MRI systems from three vendors at 1.5 T and 3 T. Technical parameters were according to Prostate Imaging Reporting and Data System Version 2.1. ADC maps were calculated by vendor specific algorithms. Absolute and relative differences in ADC from the phantom-ADC were calculated and differences between sequences were tested. RESULTS: At 3 T absolute differences from phantom given ADC (∼1,000 and âˆ¼ 1,600x10-6 mm2/s) were -83 - 42x10-6 mm2/s (-8.3%-4.2%) and -48 - 15x10-6 mm2/s (-3%-0.9%), respectively and at 1.5 T absolute differences were -81 - 26x10-6 mm2/s (-2.6%-8.1%) and -74 - 67x10-6 mm2/s (-4.6%-4.2%), respectively. Significant statistical differences in ADC measurements were identified between vendors in all sequences except for ssEPI and zoom at 3 T in the 1,600x10-6 mm2/s phantom chamber. Significant differences were also identified between ADC measurements at 1.5 T and 3 T in some of the sequences and vendors, but not all. CONCLUSION: The variation of ADC between different MRI systems and prostate specific DWI sequences is limited in this phantom study and without apparent clinical relevance. However, prospective multicenter studies of prostate cancer patients are needed for further investigation.

Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): the protocol for a Copenhagen IBD Inception Cohort Study.

INTRODUCTION: Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment. METHODS AND ANALYSIS: IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis. ETHICS AND DISSEMINATION: This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.

Diffusion-weighted MR imaging in chronic non-bacterial osteitis: Proof-of-concept of the apparent diffusion coefficient as an outcome measure.

BACKGROUND: The apparent diffusion coefficient (ADC), as determined by whole-body diffusion-weighted MRI, may be useful as an outcome measure for monitoring response to treatment in chronic non-bacterial osteitis. PURPOSE: To test and demonstrate the feasibility of ADC-measurement methods for use as outcome measure in chronic non-bacterial osteitis. MATERIALS AND METHODS: Using data from a randomized pilot study, feasibility of change-score ADC between baseline and second MRI (ΔADC12) and third MRI (ΔADC13) as outcome measure was assessed in three settings: "whole-lesion," "single-slice per lesion," and "index-lesion per patient". Bone marrow edema lesions were depicted on short tau inversion recovery sequence at baseline and copied to ADC maps at the three time-points. Correlations between the three settings were measured as were analysis of variances. Discriminant validity was assessed as inter- and intra-observer reproducibility and smallest detectable change. RESULTS: 12 subjects were enrolled, and MRI was performed at baseline and weeks 12 and 36. Pearson correlation was high (r > 0.86; p ≤ 0.01) for ΔADC between single-slice-whole-lesion and whole-lesion-index-lesion and tended to be significant for single-slice-index-lesion settings (p = 0.06). For ΔADC12 and ΔADC13, Bland-Altman plots showed small differences (0.02, 0.03) and narrow 95% limits-of-agreement (-0.13-0.09, -0.07-0.05 µm2/s) between whole-lesion and single-slice ROI settings. Inter-observer reproducibility measured by intra-class correlation coefficient was poor-to-fair (range: 0.09-0.31), whereas intra-observer reproducibility was good-to-excellent (range: 0.67-0.90). Smallest detectable changes were between 0.21-0.28 µm2/s. CONCLUSION: ADC change-score as outcome measure was feasible, and the single-slice per lesion ROI setting performed almost equally to whole-lesion setting resulting in reduced assessment time.

Development and Validation of 3 Preliminary MRI Sacroiliac Joint Composite Structural Damage Scores in a 5-year Longitudinal Axial Spondyloarthritis Study.

OBJECTIVE: In axial spondyloarthritis (axSpA), sacroiliac joint (SIJ) erosion is often followed by fat metaplasia in an erosion cavity (backfill), and subsequently ankylosis. We aimed to combine the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ structural score for erosion, backfill, and ankylosis into 3 versions of a novel preliminary axSpA magnetic resonance imaging (MRI) SIJ Composite Structural Damage Score (CSDS) and to test these. METHODS: Thirty-three patients with axSpA, followed for 5 years after initiation of tumor necrosis factor inhibitor, had MRIs of the SIJs at baseline, and yearly thereafter. Three versions of CSDS were calculated based on different weightings of erosion, backfill, and ankylosis: (1) equal weighting: CSDSequal = (erosion × 0.5) + backfill + ankylosis; (2) advanced stages weighting more: CSDSstepwise = (erosion × 1) + (backfill × 4) + (ankylosis × 6); and (3) advanced stages overruling earlier stages ("hierarchical") with "<" meaning "overruled by": CSDShierarchical = (erosion × 1) < (backfill × 4) < (ankylosis × 6). RESULTS: At baseline, all CSDS correlated positively with SPARCC fat and ankylosis scores and modified New York radiography grading, and negatively with the Bath Ankylosing Spondylitis Disease Index and SPARCC SIJ inflammation scores. CSDSstepwise and CSDShierarchical (not CSDSequal) correlated positively with symptom duration and the Bath Ankylosing Spondylitis Metrology Index, and closer with SPARCC ankylosis score and modified New York radiography grading than CSDSequal. The adjusted annual progression rate for CSDSstepwise and CSDShierarchical (not CSDSequal) was higher the first year compared with fourth year (P = 0.04 and P = 0.01). Standardized response mean (baseline to Week 46) was moderate for CSDShierarchical (0.64) and CSDSstepwise (0.59) and small for CSDSequal (0.25). CONCLUSION: Particularly CSDSstepwise and CSDShierarchical showed construct validity and responsiveness, encouraging further validation in larger clinical trials. The potential clinical implication is assessment of SIJ damage progression by 1 composite score.

Whole-body Magnetic Resonance Imaging in Psoriatic Arthritis, Rheumatoid Arthritis, and Healthy Controls: Interscan, Intrareader, and Interreader Agreement and Distribution of Lesions.

OBJECTIVE: Whole-body MRI (WBMRI) is a promising technique for monitoring patients' global disease activity in inflammatory joint diseases. The validation of WBMRI is limited; no studies have evaluated the test-retest agreement (interscan agreement) and only a few have assessed the intra- and interreader agreement. Therefore, we first examined the interscan agreement of WBMRI in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and healthy controls (HC); and second, we evaluated the intra- and interreader agreement and agreement with conventional hand MRI and determined the distribution of lesions. METHODS: WBMRI was performed twice at a 1-week interval in 14 patients with PsA, 10 with RA, and 16 HC. Images were anonymized and read in pairs with unknown chronological order by experienced readers according to the Outcome Measures in Rheumatology (OMERACT) WBMRI, Canada-Denmark MRI, and the RA MRI scoring system (RAMRIS) and the PsA MRI scoring system (PsAMRIS). Ten image sets were reanonymized for assessment of intra- and interreader agreement. Agreement was calculated on lesion level by percentage exact agreement (PEA) and Cohen κ, and for sum scores by absolute agreement, single-measure intraclass correlation coefficient (ICC). RESULTS: WBMRI of the spine and peripheral joints and entheses generally showed moderate to almost perfect interscan agreement with PEA ranging from 95% to 100%, κ 0.71-1.00, and ICC 0.95 to 1.00. Intra- and interreader data generally showed moderate to almost perfect agreement. Agreement with conventional MRI varied. More lesions were found in patients than in HC. CONCLUSION: WBMRI showed good interscan agreement, implying that repositioning of the patient between examinations does not markedly affect scoring of lesions. Intra- and interreader agreement were moderate to almost perfect.

Validation of assessment methods for the apparent diffusion coefficient in a clinical trial of axial spondyloarthritis patients treated with golimumab.

PURPOSE: To compare three region-of-interest (ROI) settings in the assessment of ADC in a clinical trial, and to evaluate the effectiveness of ADC in assessing therapy-induced changes and predicting clinical outcomes. METHODS: In a 52-week clinical trial involving patients with axial spondyloarthritis, mean sacroiliac joint (SIJ) ADC measurements using structured, lesion-based, and index-lesion ROI-settings were assessed at baseline and weeks 4, 16, and 52. Variation among the three ROI-settings, correlations with Spondyloarthritis Research Consortium of Canada (SPARCC)-bone marrow edema (BME) SIJ inflammation indices, standardized response means (SRMs), and effectiveness in predicting clinical outcomes were analyzed. RESULTS: Forty of the 53 patients had at least one assessable SIJ lesion on ADC at baseline. The mean of the structured ROI ADC (ADCstruc) was 230 µmm2/s (standard deviation [SD] = 120). This was significantly lower (p < 0.01) than the means of the lesion-based ROI ADC (ADClesion = 420 µmm2/s, SD = 210) and index-lesion ROI ADC (ADCindex = 471 µmm2/s, SD = 278), which did not differ. ADC correlated with SPARCC-BME scores at baseline (p < 0.01) as did changes over time in ADC- and SPARCC-BME (p<0.05). At all follow-up time points, responsiveness was high for ADClesion (SRM > 0.92) and ADCindex (SRM > 0.87) while moderate for ADCstruc (SRM:0.54-0.67). Baseline ADC and changes in ADC did not predict clinical outcomes. CONCLUSIONS: Lesion-based and index-lesion ROI ADC could both be used to evaluate the effectiveness of tumor necrosis factor inhibitor therapy. None of the methods could predict clinical outcomes.

Dual-energy CT in gout patients: Do all colour-coded lesions actually represent monosodium urate crystals?

BACKGROUND: Dual-energy CT (DECT) can acknowledge differences in tissue compositions and can colour-code tissues with specific features including monosodium urate (MSU) crystals. However, when evaluating gout patients, DECT frequently colour-codes material not truly representing MSU crystals and this might lead to misinterpretations. The characteristics of and variations in properties of colour-coded DECT lesions in gout patients have not yet been systematically investigated. The objective of this study was to evaluate the properties and locations of colour-coded DECT lesions in gout patients. METHODS: DECT of the hands, knees and feet were performed in patients with suspected gout using factory default gout settings, and colour-coded DECT lesions were registered. For each lesion, properties [mean density (mean of Hounsfield Units (HU) at 80 kV and Sn150kV), mean DECT ratio and size] and location were determined. Subgroup analysis was performed post hoc evaluating differences in locations of lesions when divided into definite MSU depositions and possibly other lesions. RESULTS: In total, 4033 lesions were registered in 27 patients (23 gout patients, 3918 lesions; 4 non-gout patients, 115 lesions). In gout patients, lesions had a median density of 160.6 HU and median size of 6 voxels, and DECT ratios showed an approximated normal distribution (mean 1.06, SD 0.10), but with a right heavy tail consistent with the presence of smaller amounts of high effective atomic number lesions (e.g. calcium-containing lesions). The most common locations of lesions were 1st metatarsophalangeal (MTP1), knee and midtarsal joints along with quadriceps and patella tendons. Subgroup analyses showed that definite MSU depositions (large volume, low DECT ratio, high density) had a similar distribution pattern, whereas possible calcium-containing material (high DECT ratio) and non-gout MSU-imitating lesions (properties as definite MSU depositions in non-gout patients) were primarily found in some larger joints (knee, midtarsal and talocrural) and tendons (Achilles and quadriceps). MTP1 joints and patella tendons showed only definite MSU depositions. CONCLUSION: Colour-coded DECT lesions in gout patients showed heterogeneity in properties and distribution. MTP1 joints and patella tendons exclusively showed definite MSU depositions. Hence, a sole focus on these regions in the evaluation of gout patients may improve the specificity of DECT scans.

Whole-Body Magnetic Resonance Imaging Assessment of Joint Inflammation in Rheumatoid Arthritis-Agreement With Ultrasonography and Clinical Evaluation.

Objective: To compare joint inflammation seen by whole-body magnetic resonance imaging (WBMRI), with "whole-body" ultrasound and clinical assessments, in patients with active rheumatoid arthritis (RA) before and during tumor necrosis factor-inhibitor (TNF-I, adalimumab) treatment. Methods: In 18 patients with RA, clinical assessment for joint tenderness and swelling, WBMRI, and ultrasound were obtained at baseline and week 16. Wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP), elbow (except for WBMRI), shoulder, knee, ankle, and metatarsophalangeal joints were examined. Joint inflammation was defined by WBMRI as the presence of synovitis and/or osteitis and by ultrasound as gray-scale synovial hypertrophy grade >2 and/or color Doppler grade >1. On patient level, agreement was assessed by Spearman correlation coefficients (rho) for sum scores for 28 joints (i.e., wrists, MCPs, PIPs, elbows, shoulders, and knees) between clinical examination (DAS28CRP), ultrasound (US28), and WBMRI (WBMRI26; elbows not included). On joint level, agreement on inflammation between WBMRI, ultrasound, and clinical findings was calculated with Cohen's kappa (κ). Results: At patient level, WBMRI26 and US28 sum scores showed good correlation (rho = 0.72; p < 0.01) at baseline, but not at follow-up (rho = 0.25; p = 0.41). At joint level, moderate agreement was seen for hand joints (κ = 0.41-0.44); for other joints κ <0.40. No correlation with DAS28CRP was seen. No statistically significant correlations were observed between changes in WBMRI26, US28, and DAS28CRP during treatment. Conclusions: WBMRI and ultrasound joint inflammation sum scores at patient level showed good agreement in clinically active RA patients before TNF-I initiation, whereas agreement was poorer at joint level, and after treatment.

Test-retest repeatability of the apparent diffusion coefficient in sacroiliac joint MRI in patients with axial spondyloarthritis and healthy individuals.

BACKGROUND: The apparent diffusion coefficient (ADC) may be used as a biomarker to diagnose axial spondyloarthritis (axSpA) and monitor therapeutic response. PURPOSE: To measure the repeatability of the ADC in healthy individuals and in patients with axSpA with and without active sacroiliitis in a test-retest set-up, and to correlate ADC to conventional magnetic resonance imaging (MRI) bone marrow edema (BME) scores and clinical findings. MATERIAL AND METHODS: A total of 25 patients with axSpA and 24 sex- and age-matched healthy individuals were prospectively examined with MRI twice within 10 days. Short tau inversion recovery (STIR), T1-weighted and diffusion-weighted imaging sequences were performed. Mono-exponential ADC maps were based on four b-values: 0; 50; 500; and 800. Inter-study repeatability and intra-reader reproducibility were investigated in subgroups, as were associations with conventional MRI and clinical findings. RESULTS: The inter-study repeatability for the median ADC was moderate for all individuals (intraclass correlation coefficient [ICC] 0.66); it was good in patients with axSpA (ICC 0.79) and poor in healthy individuals (ICC 0.27). Significant differences in ADC were found between women and men (P = 0.03), and between patients with versus without BME on STIR (P = 0.01). ADC was associated with an MRI BME score and with age in women. CONCLUSION: ADC seems to be a repeatable parameter in patients with axSpA but not in healthy individuals. ADC is correlated with MRI sacroiliac joint BME score and with age in women.

Association between MRI findings and patient-reported outcomes in patients with rheumatoid arthritis in clinical remission and at relapse.

OBJECTIVE: To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse. METHODS: Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n = 70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests. RESULTS: Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P < .01), independent of clinical and radiographic measures, and was also associated with most of the hand-related HAQ items (P < .03). In multivariate models including MRI, SvH scores were not associated with PROs. MRI-assessed inflammation was not associated with PROs at remission or relapse. CONCLUSION: Magnetic resonance imaging-assessed wrist/hand damage, but not inflammation, in patients with established RA is associated with patient-reported physical impairment at remission and relapse. The amount of damage in the wrist/hand is associated with reduced hand function.

Whole-body Magnetic Resonance Imaging Inflammation in Peripheral Joints and Entheses in Axial Spondyloarthritis: Distribution and Changes during Adalimumab Treatment.

OBJECTIVE: To investigate the distribution of whole-body magnetic resonance imaging (WB-MRI) inflammatory lesions of peripheral joints and entheses, and their response to adalimumab (ADA) treatment and agreement with clinical measures of disease activity in patients with axial spondyloarthritis (axSpA). METHODS: Explorative analysis of an investigator-initiated randomized controlled trial of ADA. WB-MRI was performed at weeks 0, 6, 24, and 48. Detailed analyses of WB-MRI lesions in peripheral joints and entheses were performed, including agreement with clinical measures of disease activity. RESULTS: WB-MRI inflammatory lesions were most frequently observed in the acromioclavicular, metatarsophalangeal, and wrist joints (> 10% of joints), and at the greater trochanter, calcaneal insertion of the Achilles tendon, and ischial tuberosity (> 15% of entheses). Inflammation resolved in ≥ 2/3 of involved sternoclavicular, metacarpophalangeal, first carpometacarpal, hip, and tarsometatarsal joints, and pubic symphyses and medial femoral condyles. In contrast, inflammation resolved in ≤ 1/6 of involved acromioclavicular joints, knee joints, and supraspinatus tendon insertions at humerus. Tenderness of joints and entheses agreed poorly with WB-MRI inflammation (κ < 0.40). Joint tenderness resolved more frequently in MRI-positive than MRI-negative joints (8/13, 62% vs 9/34, 26%) after 6 weeks of active treatment. CONCLUSION: Inflammatory lesions of peripheral joints and entheses in patients with predominantly axSpA, and changes therein, can be mapped using WB-MRI, and it may contribute to differentiate between inflammatory and noninflammatory joint tenderness. (Trial registration: ClinicalTrials NCT01029847).

Dose tapering and discontinuation of biological therapy in rheumatoid arthritis patients in routine care - 2-year outcomes and predictors.

Objectives: A cohort of routine care RA patients in sustained remission had biological DMARD (bDMARDs) tapered according to a treatment guideline. We studied: the proportion of patients whose bDMARD could be successfully tapered or discontinued; unwanted consequences of tapering/discontinuation; and potential baseline predictors of successful tapering and discontinuation. Methods: One-hundred-and-forty-three patients (91% receiving TNF inhibitor and 9% a non-TNF inhibitor) with sustained disease activity score (DAS28-CRP)⩽2.6 and no radiographic progression the previous year were included. bDMARD was reduced to two-thirds of standard dose at baseline, half after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP ⩾ 2.6 and ΔDAS28-CRP ⩾ 1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level. Results: One-hundred-and-forty-one patients completed 2-year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving two-thirds of standard dose, 39 (28%) half dose and 22 (16%) having discontinued; and 54 patients (38%) were receiving full dose. ΔDAS28-CRP0-2yrs was 0.1((-0.2)-0.4) (median (interquartile range)) and mean ΔTotal-Sharp-Score0-2yrs was 0.01(1.15)(mean(s.d.)). Radiographic progression was observed in nine patients (7%). Successful tapering was independently predicted by: ⩽1 previous bDMARD, male gender, low baseline MRI combined inflammation score or combined damage score. Negative IgM-RF predicted successful discontinuation. Conclusion: By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and combined damage scores were independent predictors for successful tapering.

Inflammatory and structural changes in vertebral bodies and posterior elements of the spine in axial spondyloarthritis: construct validity, responsiveness and discriminatory ability of the anatomy-based CANDEN scoring system in a randomised placebo-controlled trial.

BACKGROUND: The Canada-Denmark (CANDEN) definitions of spinal MRI lesions allow a detailed anatomy-based evaluation of inflammatory and structural lesions in vertebral bodies and posterior elements of the spine in patients with axial spondyloarthritis (axSpA). The objective was to examine the reliability, responsiveness and discrimination of scores for spinal inflammation, fat, bone erosion and new bone formation based on the CANDEN system and to describe patterns of inflammatory and structural lesions and their temporal development. METHODS: 49 patients with axSpA from an investigator-initiated, randomised, placebo-controlled trial of adalimumab underwent spinal MRI at weeks 0/6/24/48. MR images were scored according to the CANDEN system and the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Total scores, and various subscores, were created by summing individual lesion scores. RESULTS: The CANDEN spine inflammation score had high responsiveness, similar to the SPARCC MRI spine index (Guyatt's responsiveness index 1.88 and 1.67, respectively), and discriminated between adalimumab and placebo treatment already at 6 weeks' follow-up (P=0.03). Anterior/posterior corner inflammation subscores showed similar responsiveness. Inter-reader reliability for the CANDEN spine inflammation and fat scores was good to very good for status and change scores (intraclass correlation coefficient (ICC)=0.71-0.92). Reliability for CANDEN new bone formation and erosion scores was good to very good for status scores (ICC=0.61-0.75) but, due to minimal progression, poor for change scores (ICC≤0.40). CONCLUSIONS: The CANDEN spine inflammation score showed good responsiveness, discrimination between active treatment and placebo and reliability. The CANDEN spine structural scores had good cross-sectional reliability, but longer studies are needed to investigate their sensitivity to change. TRIAL REGISTRATION NUMBER: NCT01029847; Results.

Whole-body Magnetic Resonance Imaging in Axial Spondyloarthritis: Reduction of Sacroiliac, Spinal, and Entheseal Inflammation in a Placebo-controlled Trial of Adalimumab.

OBJECTIVE: To investigate whether adalimumab (ADA) reduces whole-body (WB-) magnetic resonance imaging (MRI) indices for inflammation in the entheses, peripheral joints, sacroiliac joints, spine, and the entire body in patients with axial spondyloarthritis (axSpA). METHODS: An investigator-initiated, randomized, placebo-controlled, double-blinded 48-week followup trial included 49 patients with axSpA, who had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.0 despite treatment with nonsteroidal antiinflammatory drugs and a clinical indication for tumor necrosis factor inhibitor treatment. Patients were randomized to subcutaneous ADA 40 mg or placebo every other week for 6 weeks; thereafter, all patients received ADA. Conventional MRI and WBMRI were performed at weeks 0, 6, 24, and 48. The primary WBMRI endpoint was the proportion of patients with an improvement in WBMRI total inflammation index above the smallest detectable change (SDC) at Week 6. RESULTS: The primary WBMRI endpoint (improvement of SDC > 2.3) was met in 11 (44%) patients in the ADA group and 3 (13%) patients in the placebo group (p = 0.025, Fisher's exact test). The primary conventional MRI endpoint, the minimally important change in Spondyloarthritis Research Consortium of Canada Spine MRI Inflammation Index at Week 6, was achieved by 9 (36%) patients in the ADA group and 4 (17%) patients in the placebo group (p = 0.20). The primary clinical endpoint, BASDAI reduction > 50% or 2.0 at Week 24, was attained by 32 (65%) patients. CONCLUSION: ADA provided significant reductions in WBMRI indices of peripheral, axial, and whole-body inflammation in patients with axSpA. WBMRI is promising for objective assessment and monitoring of peripheral and axial disease activity in future clinical trials.

Development and Validation of MRI Sacroiliac Joint Scoring Methods for the Semiaxial Scan Plane Corresponding to the Berlin and SPARCC MRI Scoring Methods, and of a New Global MRI Sacroiliac Joint Method.

OBJECTIVE: To develop semiaxial magnetic resonance imaging (MRI) scoring methods for assessment of sacroiliac joint (SIJ) bone marrow edema (BME) in patients with axial spondyloarthritis, and to compare the reliability with equivalent semicoronal scoring methods. METHODS: Two semiaxial SIJ MRI scoring methods were developed based on the principles of the semicoronal Berlin and Spondyloarthritis Research Consortium of Canada (SPARCC) methods. A global quadrant-based method was also developed. Baseline and 12-week MRI of the SIJ from 51 patients participating in a randomized double-blind placebo-controlled trial of adalimumab 40 mg every other week versus placebo were scored by the semiaxial and the corresponding semicoronal methods. Results were compared by linear regression analysis. The reproducibility and sensitivity were evaluated by intraclass correlation coefficients (ICC) and smallest detectable change [SDC, absolute values and percentage of the highest observed score (SDC-HOS)]. RESULTS: Interreader and intrareader ICC were moderate to very high for semiaxial scoring methods (baseline 0.83-0.88 and 0.85-0.97; change 0.33-0.78), while high to very high for semicoronal scoring methods (baseline 0.90-0.92 and 0.93-0.97; change 0.77-0.89). Association between semiaxial and semicoronal scores were high for both the Berlin and SPARCC method (baseline: R2 = 0.93 and 0.88; change: R2 = 0.82 and 0.87, respectively), while lower for the global method (baseline: R2 = 0.79; change: R2 = 0.54). The SDC-HOS were 9.8-18.6% and 5.9-10.7% for the semiaxial and semicoronal methods, respectively. CONCLUSION: Detection of SIJ BME in the semiaxial scan plane is feasible and reproducible. However, a slightly lower reliability of all 3 semiaxial methods supports the general practice of using the coronal scan-plane in therapeutic studies.

Magnetic resonance imaging assessed inflammation in the wrist is associated with patient-reported physical impairment, global assessment of disease activity and pain in early rheumatoid arthritis: longitudinal results from two randomised controlled trials.

OBJECTIVES: To examine whether MRI assessed inflammation and damage in the wrist of patients with early rheumatoid arthritis (RA) are associated with patient-reported outcomes (PROs). METHODS: Wrist and hand MRIs of 210 patients with early RA from two investigator-initiated, randomised controlled studies (CIMESTRA/OPERA) were assessed according to the Outcome Measures in Rheumatology RA MRI score (RAMRIS) for synovitis, tenosynovitis, osteitis, bone erosions and joint space narrowing (JSN) at baseline, 1 and 5 years follow-up. These features, and changes therein, were assessed for associations with health assessment questionnaires (HAQ), patient global visual analogue scales (VAS-PtGlobal) and VAS-pain using Spearman's correlations, generalised estimating equations and univariate/multivariable linear regression analyses. MRI features were further tested for trends against specific hand-related HAQ items using Jonckheere trend tests. RESULTS: MRI inflammation, but not damage, showed statistically significant associations with HAQ, VAS-PtGlobal and VAS-pain for status and change scores, independently of C reactive protein and swollen joint count. MRI-assessed synovitis was most consistently associated with PROs, particularly VAS-PtGlobal and VAS-pain. MRI-assessed synovitis and tenosynovitis mean scores were positively associated with patient-reported difficulty to cut meat and open a milk carton (p<0.01), and similar patterns were seen for other hand-related HAQ items. Incorporating metacarpophalangeal joints in the analyses did not strengthen the associations between MRI pathology and PROs. CONCLUSIONS: MRI-assessed inflammation, but not damage, in early RA wrists is associated with patient-reported physical impairment, global assessment of disease activity and pain and influences the physical function in the hand. TRIAL REGISTRATION NUMBER: NCT00660647.

Increased galectin-3 may serve as a serologic signature of pre-rheumatoid arthritis while markers of synovitis and cartilage do not differ between early undifferentiated arthritis subsets.

BACKGROUND: Undifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings. METHODS: One hundred and eleven UA patients were followed-up for at least 12 months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminant capacity of galectin-3 against arthritis subsets. RESULTS: Galectin-3 was increased in pre-rheumatoid arthritis (RA) (4.6 µg/l, interquartile range (IQR) 3.8-5.5) versus non-RA (4.0 µg/l, IQR 3.1-4.9; p = 0.03) and controls (3.8 µg/l, IQR 3.0-4.8; p = 0.009). PIIANP was equally depressed in either subset (p < 0.01). Galectin-3 in non-RA and HYA in UA did not differ from healthy controls. In the entire UA cohort, galectin-3 correlated with the MRI bone marrow edema score, while PIIANP correlated with the MRI erosion score, and HYA with the synovitis and erosion scores. ROC curve analysis showed that baseline galectin-3 discriminated well between pre-RA and non-RA with univariate area under the curve (AUC) of 0.64 (95% confidence interval (CI) 0.53-0.76) while AUC for galectin-3 + anti-CCP increased to 0.71 (95% CI 0.59-0.83). CONCLUSIONS: Galectin-3 in serum was increased in patients with early UA of pre-RA origin. Cartilage remodeling assessed by PIIANP was diminished in UA irrespective of subsequent clinical differentiation, while HYA did not differ from controls. ROC analysis showed a potential for galectin-3 to discriminate between pre-RA and non-RA. TRIAL REGISTRATION: KF 11 315829. Registered 25 July 2006.

Biparametric versus multiparametric MRI in the diagnosis of prostate cancer.

BACKGROUND: Since multiparametric magnetic resonance imaging (mp-MRI) of the prostate exceeds 30 min, minimizing the evaluation time of significant (Gleason scores > 6) prostate cancer (PCa) would be beneficial. A reduced protocol might be sufficient for the diagnosis. PURPOSE: To study whether a short unenhanced biparametric MRI (bp-MRI) matches mp-MRI in detecting significant PCa. MATERIAL AND METHODS: A total of 204 men (median age, 65 years; mean ± SD, 64.1; range 45-75 years; median serum PSA level, 14 ng/mL; range, 2.2-120 ng/mL; median prostate volume, 60 mL; range, 23-263 mL) fulfilled the criteria for being enrolled. They underwent mp-MRI and prostate biopsy from January through June 2014. Of the included patients, 9.3% underwent prostatectomy, 90.7% had TRUS-bx, and 10.8 had MRI-targeted TRUS-bx. Two radiologists separately assessed the mp-MRI examination (T2-weighted [T2W] imaging, diffusion-weighted imaging [DWI], apparent diffusion coefficient map [ADC-map] and dynamic contrast-enhanced imaging [DCE]). Two months later, the bp-MRI version (T2W imaging, DWI, and ADC-map) was evaluated. RESULTS: Reader 1: Assessing mp-MRI: 0 false negatives, sensitivity of 1, and specificity 0.04. Assessing bp-MRI: four false negatives, sensitivity of 0.94, and specificity 0.15. Reader 2: Assessing mp-MRI: five false negatives, sensitivity of 0.93, and specificity 0.16. Assessing bp-MRI: three false negatives, sensitivity of 0.96, and specificity 0.15. Intra-reader agreement Cohen's Kappa (κ) was 0.87 for reader 1 (95% confidence interval [CI], 0.83-0.92) and 0.84 for reader 2 (95% CI 0.78-0.89). CONCLUSION: Bp-MRI is as good as mp-MRI at detecting PCa. A large prospective study seems to be strongly warranted.

Preoperative CT versus diffusion weighted magnetic resonance imaging of the liver in patients with rectal cancer; a prospective randomized trial.

Introduction. Colorectal cancer is one of the most frequent cancers in the world and liver metastases are seen in up to 19% of patients with colorectal cancers. Detection of liver metastases is not only vital for sufficient treatment and survival, but also for a better estimation of prognosis. The aim of this study was to evaluate the feasibility of diffusion weighted MRI of the liver as part of a combined MR evaluation of patients with rectal cancers and compare it with the standard preoperative evaluation of the liver with CT. Methods. Consecutive patients diagnosed with rectal cancers were asked to participate in the study. Preoperative CT and diffusion weighted MR (DWMR) were compared to contrast enhanced laparoscopic ultrasound (CELUS). Results. A total of 35 patients were included, 15 patients in Group-1 having the standard CT evaluation of the liver and 20 patients in Group-2 having the standard CT evaluation of the liver and DWMR of the liver. Compared with CELUS, the per-patient sensitivity/specificity was 50/100% for CT, and for DWMR: 100/94% and 100/100% for Reader 1 and 2, respectively. The per-lesion sensitivity of CT and DWMR were 17% and 89%, respectively compared with CELUS. Furthermore, one patient had non-resectable metastases after DWMR despite being diagnosed with resectable metastases after CT. Another patient was diagnosed with multiple liver metastases during CELUS, despite a negative CT-scan. Discussion. DWMR is feasible for preoperative evaluation of liver metastases. The current standard preoperative evaluation with CT-scan results in disadvantages like missed metastases and futile operations. We recommend that patients with rectal cancer, who are scheduled for MR of the rectum, should have a DWMR of the liver performed at the same time.