Robert Hemke

EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice

To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13u2005277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion.

Reliability and responsiveness of the Juvenile Arthritis MRI Scoring (JAMRIS) system for the knee

ObjectivesTo assess the reliability and responsiveness of a new Juvenile Arthritis MRI Scoring (JAMRIS) system for evaluating disease activity of the knee.MethodsTwenty-five juvenile idiopathic arthritis (JIA) patients with clinical knee involvement were studied using open-bore 1-T MRI. MRI features of synovial hypertrophy, bone marrow changes, cartilage lesions and bone erosions were independently scored by five readers using the JAMRIS system. In addition, the JAMRIS system was determined to be a follow-up parameter by two readers to evaluate the response to therapy in 15 consecutive JIA patients.ResultsInter-reader (ICCs 0.86–0.95) and intra-reader reliability (ICCs 0.92–1.00) for the scoring of JAMRIS features was good. Reliability of the actual scores and changes in scores over time was good for all items: ICCs 0.89–1.00, 0.87–1.00, respectively. Concerning therapy response, the mean synovial hypertrophy scores decreased significantly (mean 1.1 point; Pu2009<u20090.001, SRMu2009=u2009−0.65). No change was observed with respect to bone marrow change, cartilage lesion and bone erosion scores.ConclusionsThe JAMRIS proved to be a simple and highly reliable assessment score in the evaluation of JIA disease activity of the knee. The JAMRIS system may serve as an objective and accurate outcome measure in future research and clinical trials.Key Points• MRI is increasingly used to diagnose and assess juvenile idiopathic arthritis.• A simple and reliable scoring method would help monitor progress and research.• The Juvenile Arthritis MRI Scoring (JAMRIS) system provides reliable objective measures.• JAMRIS evaluates synovial hypertrophy, bone marrow changes, cartilage lesions and bone erosions.• The JAMRIS system can detect therapeutic response and should help future research.

The diagnostic accuracy of unenhanced MRI in the assessment of joint abnormalities in juvenile idiopathic arthritis

AbstractObjectivesTo assess the diagnostic accuracy and reliability of MRI without contrast enhancement in the evaluation of JIA knee joint abnormalities.MethodsJIA patients with clinically active knee involvement were prospectively studied using an 1-T open-bore magnet. MRI features were independently evaluated by two readers using the JAMRIS system. The first reading included unenhanced images, whereas complete image sets were available for the second reading.ResultsImaging findings from 73 patients were analysed. Agreement between Gd-enhanced (+Gd) and Gd-unenhanced (−Gd) MRI scores of bone marrow changes, cartilage lesions and bone erosions was good concerning sensitivity, specificity, negative predictive value and positive predictive value. Inter-observer agreement was good for both −Gd and +Gd scores (ICCu2009=u20090.91–1.00, 0.93–1.00, respectively). Regarding the assessment of synovial hypertrophy, specificity of −Gd was high (0.97), but the sensitivity of unenhanced MRI was only 0.62. Inter-reader agreement for +Gd MRI was ICCu2009=u20090.94; however, omitting post-Gd acquisitions increased inter-reader variation (ICCu2009=u20090.86).ConclusionsIf Gd-enhanced MRI is the reference standard, omitting Gd contrast medium is irrelevant for the assessment of bone marrow changes, cartilage lesions and bone erosions as joint abnormalities in JIA. Omitting intravenous Gd in the MRI assessment of joints in JIA is inadvisable, because it decreases the reliability of detecting synovial disease.Key Points• Magnetic resonance imaging is increasingly used to assess juvenile idiopathic arthritis.n • Synovial hypertrophy, a marker of JIA activity, is well shown by MRI.n • Omitting intravenous contrast medium decreases the reliability of synovial hypertrophy scores.n • Bone marrow, cartilage and erosions can be reliably evaluated without contrast enhancement.n • In the evaluation of JIA disease activity, unenhanced MRI is inadvisable.

Contrast-enhanced MRI compared with the physical examination in the evaluation of disease activity in juvenile idiopathic arthritis

ObjectivesTo assess the value of magnetic resonance imaging (MRI) in discriminating between active and inactive juvenile idiopathic arthritis (JIA) patients and to compare physical examination outcomes with MRI outcomes in the assessment of disease status in JIA patients.MethodsConsecutive JIA patients with knee involvement were prospectively studied using an open-bore MRI. Imaging findings from 146 JIA patients were analysed (59.6xa0% female; mean age, 12.9xa0years). Patients were classified as clinically active or inactive. MRI features were evaluated using the JAMRIS system, comprising validated scores for synovial hypertrophy, bone marrow oedema, cartilage lesions and bone erosions.ResultsInter-reader reliability was good for all MRI features (intra-class correlation coefficient [ICC]u2009=u20090.87–0.94). No differences were found between the two groups regarding MRI scores of bone marrow oedema, cartilage lesions or bone erosions. Synovial hypertrophy scores differed significantly between groups (Pu2009=u20090.016). Nonetheless, synovial hypertrophy was also present in 14 JIA patients (35.9xa0%) with clinically inactive disease. Of JIA patients considered clinically active, 48.6xa0% showed no signs of MRI-based synovitis.ConclusionsMRI can discriminate between clinically active and inactive JIA patients. However, physical examination is neither very sensitive nor specific in evaluating JIA disease activity compared with MRI. Subclinical synovitis was present in >35xa0% of presumed clinically inactive patients.Key points• MRI is sensitive for evaluating juvenile idiopathic arthritis (JIA) disease activity.• Contrast-enhanced MRI can distinguish clinically active and inactive JIA patients.• Subclinical synovitis is present in 35.9u2009% of presumed clinically inactive patients.• Physical examination is neither sensitive nor specific in evaluating JIA disease activity.

Current Status of Efforts on Standardizing Magnetic Resonance Imaging of Juvenile Idiopathic Arthritis: Report from the OMERACT MRI in JIA Working Group and Health-e-Child

Objective. To report on the progress of an ongoing research collaboration on magnetic resonance imaging (MRI) in juvenile idiopathic arthritis (JIA) and describe the proceedings of a meeting, held prior to Outcome Measures in Rheumatology (OMERACT) 12, bringing together the OMERACT MRI in JIA working group and the Health-e-Child radiology group. The goal of the meeting was to establish agreement on scoring definitions, locations, and scales for the assessment of MRI of patients with JIA for both large and small joints. Methods. The collaborative work process included premeeting surveys, presentations, group discussions, consensus on scoring methods, pilot scoring, conjoint review, and discussion of a future research agenda. Results. The meeting resulted in preliminary statements on the MR imaging protocol of the JIA knee and wrist and determination of the starting point for development of MRI scoring systems based on previous studies. It was also considered important to be descriptive rather than explanatory in the assessment of MRI in JIA (e.g., “thickening” instead of “hypertrophy”). Further, the group agreed that well-designed calibration sessions were warranted before any future scoring exercises were conducted. Conclusion. The combined efforts of the OMERACT MRI in JIA working group and Health-e-Child included the assessment of currently available material in the literature and determination of the basis from which to start the development of MRI scoring systems for both the knee and wrist. The future research agenda for the knee and wrist will include establishment of MRI scoring systems, an atlas of MR imaging in healthy children, and MRI protocol requisites.

Frequency of joint involvement in juvenile idiopathic arthritis during a 5-year follow-up of newly diagnosed patients: implications for MR imaging as outcome measure.

To assess the sequence and type of active joints in a cohort of newly diagnosed juvenile idiopathic arthritis (JIA) patients with full access to current treatment at first visit and during a follow-up period of 5-years, in order to identify an index joint/group of joints for magnetic resonance imaging in JIA. Patient charts of all consecutive newly diagnosed JIA patients with a follow-up duration of at least 5xa0years were analyzed. Patients were derived from two tertiary pediatric rheumatology centers. Patient characteristics and data concerning the presence of joints with arthritis and the use of medication were recorded. Findings from 95 JIA patients [39 (41xa0%) oligoarticular and 56 (59xa0%) polyarticular] were analyzed. At first visit, distribution of active joints among patients was as follows: knee (nxa0=xa070, 74xa0%), ankle (nxa0=xa055, 58xa0%), elbow (nxa0=xa023, 24xa0%), wrist (nxa0=xa023, 24xa0%), metacarpophalangeal (MCP) (nxa0=xa020, 21xa0%), proximal interphalangeal (PIP) (nxa0=xa013, 14xa0%), hip (nxa0=xa06, 6xa0%), shoulder (nxa0=xa05, 5xa0%), and distal interphalangeal (DIP) (nxa0=xa04, 4xa0%) joints. After a follow-up period of 5 years, the cumulative percentage of patients with specific joint involvement changed into: knee (nxa0=xa088, 93xa0%), ankle (nxa0=xa079, 83xa0%), elbow (nxa0=xa043, 45xa0%), wrist (nxa0=xa038, 40xa0%), MCP (nxa0=xa036, 38xa0%), PIP (nxa0=xa029, 31xa0%), shoulder (nxa0=xa020, 21xa0%), hip (nxa0=xa017, 19xa0%), and DIP (nxa0=xa09, 10xa0%) joints. Despite changes in treatment strategies over the years, the knee remains the most commonly involved joint at onset and during follow-up in JIA, followed by the ankle, elbow, and wrist. For the evaluation of outcome with MRI, the knee appears the most appropriate joint in JIA.

Pixel-by-pixel analysis of DCE-MRI curve shape patterns in knees of active and inactive juvenile idiopathic arthritis patients

AbstractObjectivesTo compare DCE-MRI parameters and the relative number of time–intensity curve (TIC) shapes as derived from pixel-by-pixel DCE-MRI TIC shape analysis between knees of clinically active and inactive juvenile idiopathic arthritis (JIA) patients.MethodsDCE-MRI data sets were prospectively obtained. Patients were classified into two clinical groups: active disease (nu2009=u200943) and inactive disease (nu2009=u200934). Parametric maps, showing seven different TIC shape types, were created per slice. Statistical measures of different TIC shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV), volume transfer constant (Ktrans), extravascular space fractional volume (Ve) and reverse volume transfer constant (kep) of each voxel were calculated in a three-dimensional volume-of-interest of the synovial membrane.ResultsImaging findings from 77 JIA patients were analysed. Significantly higher numbers of TIC shape 4 (Pu2009=u20090.008), median ME (Pu2009=u20090.015), MIS (Pu2009=u20090.001) and iAUC (Pu2009=u20090.002) were observed in clinically active compared with inactive patients. TIC shape 5 showed higher presence in the clinically inactive patients (Pu2009=u20090.036).ConclusionsThe pixel-by-pixel DCE-MRI TIC shape analysis method proved capable of differentiating clinically active from inactive JIA patients by the difference in the number of TIC shapes, as well as the descriptive parameters ME, MIS and iAUC.Key Points• The pixel-by-pixel TIC shape method differentiates clinically active and inactive JIA patientsn • Significantly higher numbers of TIC shape 4 were observed in clinically active patientsn • DCE-MRI parameters ME, MIS and iAUC differ between active and inactive patientsn • The pixel-by-pixel analysis method allows direct visualization of the heterogeneously distributed diseasen • The DCE-MRI TIC shape method may serve as a quantitative outcome measure

Contrast-enhanced MRI of the knee in children unaffected by clinical arthritis compared to clinically active juvenile idiopathic arthritis patients

AbstractObjectivesTo evaluate enhancing synovial thickness upon contrast-enhanced magnetic resonance imaging (MRI) of the knee in children unaffected by clinical arthritis compared with clinically active juvenile idiopathic arthritis (JIA) patients. A secondary objective was optimization of the scoring method based on maximizing differences on MRI between these groups.MethodsTwenty-five children without history of joint complaints nor any clinical signs of joint inflammation were age/sex-matched with 25 clinically active JIA patients with arthritis of at least one knee. Two trained radiologists, blinded for clinical status, independently evaluated location and extent of enhancing synovial thickness with the validated Juvenile Arthritis MRI Scoring system (JAMRIS) on contrast-enhanced axial fat-saturated T1-weighted MRI of the knee.ResultsEnhancing synovium (≥2xa0mm) was present in 13 (52xa0%) unaffected children. Using the total JAMRIS score for synovial thickening, no significant difference was found between unaffected children and active JIA patients (pu2009=u20090.091). Additional weighting of synovial thickening at the JIA-specific locations enabled more sensitive discrimination (pu2009=u20090.011).ConclusionsMild synovial thickening is commonly present in the knee of children unaffected by clinical arthritis. The infrapatellar and cruciate ligament synovial involvement were specific for JIA, which—in a revised JAMRIS—increases the ability to discriminate between JIA and unaffected children.Key Points• Synovial inflammation is the primary disease feature in juvenile idiopathic arthritis (JIA).• Appearance of the synovium on contrast-enhanced MRI in unaffected children is unknown.• Validation of existing scoring methods requires comparison between JIA and unaffected children.• Mild enhancing synovial thickening was detected in half of the unaffected children.n • Location-weighting for JIA-specific locations increased discriminative value of the scoring methods (pu2009=u20090.011).

Feasibility of diffusion-weighted magnetic resonance imaging in patients with juvenile idiopathic arthritis on 1.0-T open-bore MRI.

ObjectiveTo evaluate the feasibility of non-invasive diffusion-weighted imaging (DWI) of the knee of children with juvenile idiopathic arthritis (JIA) and, further, to analyze the apparent diffusion coefficient (ADC) levels to distinguish synovium from effusion.Materials and methodsStandard magnetic resonance imaging of the knee including post-contrast imaging was obtained in eight patients (mean age, 12xa0years 8xa0months, five females) using an open-bore magnetic resonance imaging system (1.0 T). In addition, axially acquired echo-planar DWI datasets (b-values 0, 50, and 600) were prospectively obtained and the diffusion images were post-processed into ADC50–600 maps. Two independent observers selected a region of interest (ROI) for both synovium and effusion using aligned post-contrast images as landmarks. Mann–Whitney U test was performed to compare ADC synovium and ADC effusion.ResultsDWI was successfully obtained in all patients. When data of both observers was combined, ADC synovium was lower than ADC effusion in the ROI in seven out of eight patients (median, 1.92u2009×u200910−3xa0mm2/s vs. 2.40u2009×u200910−3xa0mm2/s, pu2009=u20090.006, respectively). Similar results were obtained when the two observers were analyzed separately (observer 1: pu2009=u20090.006, observer 2: pu2009=u20090.04).ConclusionsIn this pilot study, on a patient-friendly 1.0-T open-bore MRI, we demonstrated that DWI may potentially be a feasible non-invasive imaging technique in children with JIA. We could differentiate synovium from effusion in seven out of eight patients based on the ADC of synovium and effusion. However, to select synovium and effusion on DWI, post-contrast images were still a necessity.

Selecting Magnetic Resonance Imaging (MRI) Outcome Measures for Juvenile Idiopathic Arthritis (JIA) Clinical Trials: First Report of the MRI in JIA Special Interest Group

Recent advances in magnetic resonance imaging (MRI) techniques have substantially improved the evaluation of joint pathologies in juvenile idiopathic arthritis (JIA). Because of the current availability of highly effective antirheumatic therapies and the unique and useful features of MRI, there is a growing need for an accurate and reproducible MRI assessment scoring system for JIA, such as the rheumatoid arthritis MRI Scoring (RAMRIS) for patients with rheumatoid arthritis (RA). To effectively evaluate the efficacy of treatment in clinical research trials, we need to develop and validate scoring methods to accurately measure joint outcomes, standardize imaging protocols for data acquisition and interpretation, and create imaging atlases to differentiate physiologic and pathologic joint findings in childhood and adolescence. Such a standardized, validated, JIA-MRI scoring method could be used as an outcome measure in clinical trials.