Charlotte M. Nusman

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.

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 (n = 43) and inactive disease (n = 34). 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 (P = 0.008), median ME (P = 0.015), MIS (P = 0.001) and iAUC (P = 0.002) were observed in clinically active compared with inactive patients. TIC shape 5 showed higher presence in the clinically inactive patients (P = 0.036).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 patients • Significantly higher numbers of TIC shape 4 were observed in clinically active patients • DCE-MRI parameters ME, MIS and iAUC differ between active and inactive patients • The pixel-by-pixel analysis method allows direct visualization of the heterogeneously distributed disease • The DCE-MRI TIC shape method may serve as a quantitative outcome measure

Automated determination of bone age and bone mineral density in patients with juvenile idiopathic arthritis: a feasibility study

IntroductionChronic inflammation combined with glucocorticoid treatment and immobilization puts juvenile idiopathic arthritis (JIA) patients at risk of impaired growth and reduced bone mineral density (BMD). Conventional methods for evaluating bone age and BMD are time-consuming or come with additional costs and radiation exposure. In addition, an automated measurement of bone age and BMD is likely to be more consistent than visual evaluation. In this study, we aimed to evaluate the feasibility of an automated method for determination of bone age and (cortical) bone mineral density (cBMD) in severely affected JIA patients. A secondary objective was to describe bone age and cBMD in this specific JIA population eligible for biologic treatment.MethodsIn total, 69 patients with standard hand radiographs at the start of etanercept treatment and of calendar age within the reliability ranges (2.5 to 17 years for boys and 2 to 15 years for girls) were extracted from the Dutch Arthritis and Biologicals in Children register. Radiographs were analyzed using the BoneXpert method, thus automatically determining bone age and cBMD expressed as bone health index (BHI). Agreement between measurements of the left- and right-hand radiographs and a repeated measurement of the left hand were assessed with the intraclass correlation coefficient (ICC). Regression analysis was used to identify variables associated with Z-scores of bone age and BHI.ResultsThe BoneXpert method was reliable in the evaluation of radiographs of 67 patients (radiographs of 2 patients were rejected because of poor image quality). Agreement between left- and right-hand radiographs (ICC = 0.838 to 0.996) and repeated measurements (ICC = 0.999 to 1.000) was good. Mean Z-scores of bone age (-0.36, P = 0.051) and BHI (-0.85, P < 0.001) were lower compared to the healthy population. Glucocorticoid use was associated with delayed bone age (0.79 standard deviation (SD), P = 0.028), and male gender was associated with a lower Z-score of BHI (0.65 SD, P = 0.021).ConclusionsBoneXpert is an easy-to-use method for assessing bone age and cBMD in patients with JIA, provided that radiographs are of reasonable quality and patients’ bone age lies within the age ranges of the program. The population investigated had delayed bone maturation and lower cBMD than healthy children.

MRI Protocol for the Assessment of Juvenile Idiopathic Arthritis of the Wrist: Recommendations from the OMERACT MRI in JIA Working Group and Health-e-Child

To the Editor: Magnetic resonance imaging (MRI) is the only imaging tool that allows us to assess all relevant structures in juvenile idiopathic arthritis (JIA): the synovium, cartilage, bone, ligaments, and tendon sheaths. The interpretation of the MRI of the wrist in patients with JIA is challenging because of the complex anatomy and the presence of normal variants mimicking pathology1,2. There is a need for a consensus of MRI interpretation in children with JIA and a universal protocol for MRI acquisition, which can enable uniformity of identification of all involved structures. From 2012 onward, an international collaborative network of clinical and radiological experts on imaging in JIA has set out to standardize the challenging MRI acquisition and interpretation of JIA … Address correspondence to Dr. C.M. Nusman, Academic Medical Center, Radiology, Meibergdreef 9, Amsterdam, 1105 AZ, the Netherlands. E-mail: c.m.nusman{at}amc.nl

Dynamic contrast-enhanced magnetic resonance imaging of the wrist in children with juvenile idiopathic arthritis.

BackgroundDynamic contrast-enhanced MRI provides information on the heterogeneity of the synovium, the primary target of disease in children with juvenile idiopathic arthritis (JIA).ObjectiveTo evaluate the feasibility of dynamic contrast-enhanced MRI in the wrist of children with JIA using conventional descriptive measures and time-intensity-curve shape analysis. To explore the association between enhancement characteristics and clinical disease status.Materials and methodsThirty-two children with JIA and wrist involvement underwent dynamic contrast-enhanced MRI with movement-registration and were classified using validated criteria as clinically active (n = 27) or inactive (n = 5). Outcome measures included descriptive parameters and the classification into time-intensity-curve shapes, which represent the patterns of signal intensity change over time. Differences in dynamic contrast-enhanced MRI outcome measures between clinically active and clinically inactive disease were analyzed and correlation with the Juvenile Arthritis Disease Activity Score was determined.ResultsComprehensive evaluation of disease status was technically feasible and the quality of the dynamic dataset was improved by movement registration. The conventional descriptive measure maximum enhancement differed significantly between clinically active and inactive disease (P = 0.019), whereas time-intensity-curve shape analysis showed no differences. Juvenile Arthritis Disease Activity Score correlated moderately with enhancing volume (P = 0.484).ConclusionDynamic contrast-enhanced MRI is a promising biomarker for evaluating disease status in children with JIA and wrist involvement. Conventional descriptive dynamic contrast-enhanced MRI measures are better associated with clinically active disease than time-intensity-curve shape analysis.

Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis: a promising imaging biomarker as an alternative to gadolinium-based contrast agents

AbstractObjectivesTo compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA).MethodsRegions of interest (ROI) were drawn in the synovium of JIA patients on T1 DCE and T2 DWI, followed by extraction of the maximum enhancement (ME), maximum initial slope (MIS), time to peak (TTP), % of different time intensity curve shapes (TIC) and apparent diffusion coefficient (ADC) of the ROIs. Mann-Whitney-U test was used for comparing parameters between MRI-active and -inactive patients (defined by the juvenile arthritis MRI scoring system). Spearman’s rank was used to analyse the correlation between DCE and DWI.ResultsThirty-five JIA patients (18 MRI active and 17 MRI inactive) were included. Median age was 13.1 years and 71% were female. ME, MIS, TTP, % TIC 5 and ADC were significantly different in MRI-active versus MRI-inactive JIA with median ADC 1.49 × 10-3mm2/s in MRI-active and 1.25 × 10-3mm2/s in MRI-inactive JIA, p = 0.001, 95% confidence interval of difference in medians =0.11-0.53 × 10-3mm2/s. ADC correlated to ME, MIS and TIC 5 shapes (r = 0.62, r = 0.45, r = -0.51, respectively, all p < 0.05).ConclusionsSimilar to DCE parameters, DWI-derived ADC is significantly different in MRI-active JIA as compared to MRI-inactive JIA. The non-invasiveness of DWI combined with its possibility to detect synovial inflammation shows the potential of DWI.Key Points• MRI can quantify: dynamic contrast-enhanced and diffusion-weighted MRI can quantify synovitis • Both DWI and DCE can differentiate active from inactive JIA • The DWI-derived apparent diffusion coefficient (ADC) is higher in active JIA • DWI is non-invasive and thus safer and more patient-friendly • DWI is a potentially powerful and non-invasive imaging biomarker for JIA

Magnetic Resonance Imaging (MRI) of the Knee as an Outcome Measure in Juvenile Idiopathic Arthritis: An OMERACT Reliability Study on MRI Scales

Objective. There is increasing evidence that early therapeutic intervention improves longterm joint outcome in juvenile idiopathic arthritis (JIA). Given the existence of highly effective treatments, there is an urgent need for reliable and accurate measures of disease activity and joint damage in JIA. Our objective was to assess the reliability of 2 magnetic resonance imaging (MRI) scoring methods: the Juvenile Arthritis MRI Scoring (JAMRIS) system and the International Prophylaxis Study Group (IPSG) consensus score, for evaluating disease status of the knee in patients with JIA. Methods. Four international readers independently scored an MRI dataset of 25 JIA patients with clinical knee involvement. Synovial thickening, joint effusion, bone marrow changes, cartilage lesions, bone erosions, and subchondral cysts were scored using the JAMRIS and IPSG systems. Further, synovial enhancement, infrapatellar fat pad heterogeneity, tendinopathy, and enthesopathy were scored. Interreader reliability was analyzed by using the generalized κ, ICC, and the smallest detectable difference (SDD). Results. ICC regarding interreader reliability ranged from 0.33 (95% CI 0.12–0.52, SDD = 0.29) for enthesopathy up to 0.95 (95% CI 0.92–0.97, SDD = 3.19) for synovial thickening. Good interreader reliability was found concerning joint effusion (ICC 0.93, 95% CI 0.89–0.95, SDD = 0.51), synovial enhancement (ICC 0.90, 95% CI 0.85–0.94, SDD = 9.85), and bone marrow changes (ICC 0.87, 95% CI 0.80–0.92, SDD = 10.94). Moderate to substantial reliability was found concerning cartilage lesions and bone erosions (ICC 0.55–0.72, SDD 1.41–13.65). Conclusion. The preliminary results are promising for most of the scored JAMRIS and IPSG items. However, further refinement of the scoring system is warranted for unsatisfactorily reliable items such as bone erosions, cartilage lesions, and enthesopathy.

Contrast-enhanced MRI findings of the knee in healthy children; establishing normal values

ObjectivesTo define normative standards for the knee in healthy children using contrast-enhanced MRI, focusing on normal synovial membrane thickness. Secondly, presence of joint fluid and bone marrow oedema was evaluated.MethodsFor this study, children without disorders potentially resulting in (accompanying) arthritis were included. Patients underwent clinical assessments, followed by contrast-enhanced MRI. MRI features were evaluated in consensus using the Juvenile Arthritis MRI Scoring (JAMRIS) system. Additionally, the presence of joint fluid was evaluated. No cartilage lesions or bone abnormalities were observed.ResultsWe included 57 healthy children. The overall mean thickness of the normal synovial membrane was 0.4 mm (min–max; 0.0–1.8mm). The synovium was thickest around the cruciate ligaments and retropatellar and suprapatellar regions. The mean overall diameter of the largest pocket of joint fluid was 2.8 mm (min–max; 0.9–8.0mm). Bone marrow changes were observed in three children (all in the apex patellae).ConclusionsThe normal synovial membrane was maximally 1.8 mm thick, indicating that the JAMRIS cut-off value of 2 mm can be considered a valid measure for evaluating synovial hypertrophy. Some joint fluid and bone marrow changes suggestive of bone marrow oedema in the apex patellae can be seen in healthy children.Key Points• Knowledge on the normal synovial appearance using contrast-enhanced MR is lacking.• In healthy children, normal synovial membrane is maximally 1.8 mm thick.• Normal synovium is thickest around the cruciate ligaments, retropatellar and suprapatellar.• Bone marrow oedema in the apex patellae is seen in healthy children.

Construct validity of pixel-by-pixel DCE-MRI: Correlation with conventional MRI scores in juvenile idiopathic arthritis

OBJECTIVES To assess the capability of the pixel-by-pixel DCE-MRI time intensity curve (TIC)-shape analysis method in the evaluation of juvenile idiopathic arthritis (JIA) disease activity by correlating DCE-MRI parameters with semi-quantitative conventional-MRI scores of synovitis. METHODS Clinical, laboratory, and (DCE)-MRI datasets of 85 JIA patients were prospectively obtained. TIC-shapes of each voxel were classified into one of seven predefined color-coded TIC shape categories. Spatial information on the relative amount of TIC-shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV) was calculated of the synovial membrane. The grade of synovitis was scored on conventional MR images by two readers using the validated JAMRIS system. The Bonferroni method was used to correct for multiple testing, therefore, a P value of <0.0056 is considered significant (0.05/9=0.0056). RESULTS The semi-quantitative JAMRIS synovitis score correlated substantially with the ME, EV, and iAUC (Rs=0.658, P<0.001; Rs=0.618, P<0.001; Rs=0.639, P<0.001), and moderately with MIS (Rs=0.453, P<0.001). A poor correlation was observed between the relative number of TIC-shapes 2-5 and the JAMRIS synovitis score (Rs=0.209, P=0.054; Rs=0.328, P=0.002; Rs=0.241, P=0.023; Rs=-0.241, P=0.026). CONCLUSION In this explorative study, both TIC shape and semi-quantitative DCE-MRI analysis methods showed moderate to substantial correlations with conventional MRI scores of disease activity, indicating that this methods are feasible. Further research is warranted whether DCE-MRI holds potential to become an objective and quantitative method for the evaluation of disease activity in JIA.

Bone health of patients with juvenile idiopathic arthritis: a comparison between dual-energy X-ray absorptiometry and digital X-ray radiogrammetry

OBJECTIVES Juvenile idiopathic arthritis (JIA) affects bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) is the most widely used technique to determine BMD. Digital X-ray radiogrammetry (DXR) is a feasible method for determination of cortical BMD on hand radiographs. This study aimed to compare DXR and DXA in the assessment of BMD in JIA patients. METHODS Thirty-five JIA patients with available DXA and hand radiograph within the same time period were included from the Dutch Arthritis and Biologicals in Children register. Outcome measures for BMD were Bone Health Index from DXR and BMD total body, BMD lumbar spine and Bone Mineral Apparent Density from DXA. All measures were transformed to Z-scores. Correlations were assessed with Pearson correlation coefficients. RESULTS Median age of the patients (60% female) was 11.7 years. Pearson correlation coefficient was significant for the absolute scores: 0.568-0.770 (p<0.001). No significant correlation was found between the Z-scores of DXA and DXR. CONCLUSIONS The BMD assessment from the DXR was correlated to DXA measures in a cohort of JIA patients, although only in absolute scores. Future steps for implementation of DXR in clinical practice include evaluation of responsiveness to change, predictive value and comparison with other imaging techniques.