Double inversion recovery MRI versus contrast-enhanced MRI for evaluation of knee synovitis in juvenile idiopathic arthritis.

BACKGROUND: Double inversion recovery (DIR) MRI has the potential to accentuate the synovium without using contrast agents, as it allows simultaneous signal suppression of fluid and fat. The purpose of this study was (1) to compare DIR MRI to conventional contrast-enhanced (CE) MRI for delineation of the synovium in the knee in children with juvenile idiopathic arthritis (JIA) and (2) to assess the agreement between DIR MRI and CE-MRI regarding maximal synovial thickness measurements. RESULTS: In this prospective study, 26 children with JIA who consecutively underwent 3.0-T knee MRI between January 2018 and January 2021 were included (presence of knee arthritis: 13 [50%]; median age: 14 years [interquartile range [IQR]: 11-17]; 14 girls). Median confidence to depict the synovium (0-100 mm visual analogue scale; scored by 2 readers [consensus based]) was 88 (IQR: 79-97) for DIR MRI versus 100 (IQR: 100-100) for CE-MRI (p value = < .001). Maximal synovial thickness per child (millimeters; scored by 4 individual readers) on DIR MRI was greater (p value = < .001) in the children with knee arthritis (2.4 mm [IQR: 2.1-3.1]) than in those without knee arthritis (1.4 mm [IQR: 1.0-1.6]). Good inter-technique agreement for maximal synovial thickness per child was observed (rs = 0.93 [p value = < .001]; inter-reader reliability: ICC DIR MRI = 0.87 [p value = < .001], ICC CE-MRI = 0.90 [p value = < .001]). CONCLUSION: DIR MRI adequately delineated the synovium in the knee of children with JIA and enabled synovial thickness measurement similar to that of CE-MRI. Our results demonstrate that DIR MRI should be considered as a child-friendly alternative to CE-MRI for evaluation of synovitis in children with (suspected) JIA.

Synovial signal intensity on static contrast-enhanced MRI for evaluation of disease activity in juvenile idiopathic arthritis - A look at the bright side of the knee.

BACKGROUND: Knowledge on the role of synovial signal intensity (SI) grading on static contrast-enhanced (CE) MRI of the knee for assessment of disease activity in juvenile idiopathic arthritis (JIA) is lacking. OBJECTIVES: To assess the value of synovial SI on static CE-MRI of the knee for evaluation of disease activity in children with JIA. MATERIALS AND METHODS: Children with clinically inactive and clinically active JIA who underwent static CE-MRI of the knee were included. Synovial SI was evaluated on post-contrast T1-weighted fat-saturated images using a 0.02 cm2 region of interest drawn in the area of the synovium that contained visually the highest SI. To control for potential time-dependent post-contrast enhancement variability, a ratio between the SI of the synovium to the musculus gastrocnemius was calculated. RESULTS: We included 427 JIA patients (clinically inactive JIA: 150 [35,1%]; clinically active JIA: 277 [64.9%]), 65.3% female, with a mean age of 13.3 ± 3.2 years. Mean SI synovium-to-muscle ratio was 2.1 ± 0.7 in patients with clinically inactive JIA versus 2.2 ± 0.8 in patients with clinically active JIA. Subgroup analysis showed no significant difference in SI synovium-to-muscle ratio between JIA patients with clinically inactive disease and JIA patients with clinically active disease (p-value 0.22). CONCLUSIONS: Evaluation of the brightness of the synovium on static CE-MRI of the knee for assessment of JIA disease activity should be avoided, as this might lead to incorrect clinical conclusions.

Comparison of contrast-enhanced MRI features of the (teno)synovium in the wrist of patients with juvenile idiopathic arthritis and pediatric controls.

To directly compare and describe the differences between juvenile idiopathic arthritis (JIA) patients and pediatric controls regarding features of the synovial and tenosynovial membrane on contrast-enhanced magnetic resonance imaging (MRI) of the wrist. T1-weighted contrast-enhanced MRI scans of 25 JIA patients with clinically active wrist arthritis and 25 children without a history of joint complaints nor any clinical signs of joint inflammation were evaluated by two readers blinded to clinical data. The synovium was scored at five anatomical sites based on thickening of the synovium (0-3 scale) and synovial enhancement (0-2 scale). Thickening and/or enhancement of the tenosynovium was scored at four anatomical sites using a 0-3 scale. Significantly higher scores for synovial thickening (median 4 vs. 1, p < 0.001) and synovial enhancement (median 4 vs. 1, p < 0.001) are found in the wrist of JIA patients as compared to controls. JIA patients experienced the highest synovial scores at the mid-/inter-carpal, 2nd -5th carpometacarpal, and radiocarpal joints. No significant difference in tenosynovial scores is found between both groups (median 0 vs. 0, p = 0.220). This study highlights the higher synovial thickening/enhancement scores on contrast-enhanced MRI of the wrist in JIA patients compared to pediatric controls. Tenosynovial thickening and/or enhancement was rarely present in both groups. In JIA patients, synovial thickening and enhancement were particularly present at three anatomical sites. These results substantially support rheumatologists and radiologists when navigating through MRI of the wrist in search for JIA disease activity.

Exploring contrast-enhanced MRI findings of the clinically non-inflamed symptomatic pediatric wrist.

BACKGROUND: Knowledge of the synovial and tenosynovial appearance of the clinically non-arthritic symptomatic juvenile wrist using contrast-enhanced magnetic resonance imaging (MRI) is sparse. OBJECTIVES: To analyze contrast-enhanced MRI findings of the clinically non-inflamed symptomatic pediatric wrist, focusing on the enhancing synovial and tenosynovial membrane. To evaluate the coexistent presence of (teno)synovial enhancement, joint fluid, bony depressions and medullary changes suggestive of bone marrow edema. MATERIALS AND METHODS: We included 20 children (15 girls; age range: 7.5-17.6 years) who underwent contrast-enhanced MRI of the wrist, based on initial clinical indication, and eventually turned out to be unaffected by arthritic or orthopedic disorders. Various imaging characteristics of the synovium, tenosynovium, joint fluid, bone tissue and bone marrow were evaluated using existing MRI scoring systems. RESULTS: In 3/20 (15%) children, mild or moderate-severe synovial enhancement was observed and 2/20 (10%) children showed mild tenosynovial enhancement/thickening. Joint fluid (11/20 children; 55%), bony depressions (20/20 children; 100%) and medullary changes suggestive of bone marrow edema (6/20; 30%) were found in a substantial percentage of children. The most frequently observed combination of coexisting imaging characteristics was bony depressions with ≥2 mm joint fluid, which was found in 7/20 (35%) children. Simultaneous presence of synovial and tenosynovial enhancement/thickening, bony depressions and medullary changes suggestive of bone marrow edema was observed in one child. CONCLUSION: Several juvenile idiopathic arthritis-relevant MRI characteristics can be observed in the clinically non-inflamed symptomatic pediatric wrist.

Experiences, perspectives and expectations of adolescents with juvenile idiopathic arthritis regarding future work participation; a qualitative study.

BACKGROUND: Having Juvenile idiopathic Arthritis (JIA) has widespread implications for a person's life. Patients have to deal with recurring arthritis, characterized by pain often accompanied by a loss of energy. Since JIA often persists into adulthood, patients with JIA are likely to encounter difficulties in their working life. We expect that the experiences in school life may be comparable to the barriers and opportunities which patients affected by JIA encounter in adult working life. Therefore, the aim of this study was to elicit the experiences during school life and the perspectives and expectations regarding future work participation of adolescents with JIA. METHODS: This study used individual, semi-structured interviews and followed a predefined interview guide. Participants between 14 and 18 years of age (n = 22) were purposively selected to achieve a broad range of participant characteristics. Open coding was performed, followed by axial coding and selective coding. RESULTS: Great differences were seen in the support and understanding that adolescents received in dealing with JIA at school, leisure activities and work. Varying approaches were mentioned on how to pursue a desired vocation. Perspectives regarding disclosure varied. Participants wished to be approached like any other healthy adolescent. Expectations regarding work participation were positively expressed. CONCLUSION: This study showed that participants often disregarded having JIA when making plans for their future career. Facilitating an open discussion about the possible limitations accompanying JIA with educators and employers might prevent overburden and increase the chance of starting a career which would accommodate the patient with JIA in the near and distant future.

Juvenile Idiopathic Arthritis: Diffusion-weighted MRI in the Assessment of Arthritis in the Knee.

Background Diffusion-weighted imaging (DWI) can depict the inflamed synovial membrane in arthritis. Purpose To study the diagnostic accuracy of DWI for the detection of arthritis compared with the clinical reference standard and to compare DWI to contrast material-enhanced MRI for the detection of synovial inflammation. Materials and Methods In this institutional review board-approved prospective study, 45 participants with juvenile idiopathic arthritis (JIA) or suspected of having JIA (seven boys, 38 girls; median age, 14 years [interquartile range, 12-16 years]) were included between December 2015 and December 2018. Study participants underwent pre- and postcontrast 3.0-T MRI of the knee with an additional DWI sequence. For the clinical reference standard, a multidisciplinary team determined the presence or absence of arthritis on the basis of clinical, laboratory, and imaging findings (excluding DWI). Two data sets were scored by two radiologists blinded to all clinical data; data set 1 contained pre- and postcontrast sequences (contrast-enhanced MRI), and data set 2 contained precontrast and DWI sequences (DWI). Diagnostic accuracy was determined by comparing the scores of the DWI data set to those of the clinical reference standard. Second, DWI was compared with contrast-enhanced MRI regarding detection of synovial inflammation. Results Sensitivity for detection of arthritis for DWI was 93% (13 of the 14 participants with arthritis were correctly classified with DWI; 95% confidence interval [CI]: 64%, 100%) and specificity was 81% (25 of 31 participants without arthritis were correctly classified with DWI; 95% CI: 62%, 92%). Scores for synovial inflammation at DWI and contrast-enhanced MRI agreed in 37 of 45 participants (82%), resulting in a sensitivity of 92% (12 of 13 participants; 95% CI: 62%, 100%) and specificity of 78% (25 of 32 participants; 95% CI: 60%, 90%) with DWI when contrast-enhanced MRI was considered the reference standard. Conclusion Diffusion-weighted imaging (DWI) was accurate in detecting arthritis in pediatric participants with juvenile idiopathic arthritis (JIA) or suspected of having JIA and showed agreement with contrast-enhanced MRI. The results indicate that DWI could replace contrast-enhanced MRI for imaging of synovial inflammation in this patient group. © RSNA, 2020 Online supplemental material is available for this article.

MRP8/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis.

OBJECTIVE: To study two neutrophil activation markers, myeloid-related protein (MRP) 8/14 and neutrophil elastase (NE), for their ability to predict treatment response and flare in patients with JIA. METHODS: Using samples from two cohorts (I and II), we determined MRP8/14 and NE levels of 32 (I) and 81 (II) patients with new-onset, DMARD-naïve arthritis and compared patients who responded to treatment (defined as fulfilling ≥ adjusted ACRpedi50 response and/or inactive disease) with non-responders (defined as fulfilling < adjusted ACRpedi50 response and/or active disease) at 6 and 12 months. Secondly, we compared biomarker levels of 54 (I) and 34 (II) patients with clinically inactive disease who did or did not suffer from a flare of arthritis after 6 or 12 months. Receiver operating characteristic analyses were carried out to study the predictive value of MRP8/14 and NE for treatment response and flare. RESULTS: For both cohorts, baseline MRP8/14 and NE levels for patients who did or did not respond to treatment were not different. Also, MRP8/14 and NE levels were not different in patients who did or did not flare. Receiver operating characteristic analysis of MRP8/14 and NE demonstrated areas under the curve <0.7 in both cohorts. CONCLUSION: In our cohorts, MRP8/14 and NE could not predict treatment response. Also, when patients had inactive disease, neither marker could predict flares.

Prolonged time between intravenous contrast administration and image acquisition results in increased synovial thickness at magnetic resonance imaging in patients with juvenile idiopathic arthritis.

BACKGROUND: Post-contrast synovial thickness measurement is necessary for scoring disease activity in juvenile idiopathic arthritis (JIA). However, the timing of post-contrast sequences varies widely among institutions. This variation in timing could influence thickness measurements. OBJECTIVE: To measure thickness of the synovial membrane on early and late post-contrast knee magnetic resonance (MR) images of patients with JIA. MATERIALS AND METHODS: Dynamic contrast-enhanced T1-weighted knee MR images of 53 children with JIA with current or past knee arthritis were used to study synovial thickness at time point 1 (about 1 min) and time point 2 (about 5 min after contrast administration). Two experienced readers, who were blinded for the time point, independently measured synovial thickness at a predefined, marked location in the patellofemoral compartment on randomized images. Synovial thickness at the two time points was compared using the Wilcoxon signed rank test. Repeatibility of the synovial thickness measurements was studied using intraclass correlation coefficients and Bland-Altman plots. RESULTS: Median synovial thickness of the 53 patients (median age: 13.5 years, 59% female) increased with prolonged post-contrast interval with a synovial thickness of 1.4 mm at time point 1 and a synovial thickness of 1.5 mm at time point 2 (P<0.001). Repeated synovial thickness measurements showed an intraclass correlation coefficient (ICC) of 0.75, P<0.05 for time point 1 and an ICC of 0.91, P<0.05 for time point 2. CONCLUSION: Post-contrast synovial membrane thickness measurements are time-dependent. Therefore, standardization of post-contrast image acquisition timing is important to achieve consistent grading of synovial inflammation.

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

The original version of this article, published on 12 June 2017, unfortunately contained a mistake.

Normal MRI findings of the knee in patients with clinically active juvenile idiopathic arthritis.

OBJECTIVE: In a number of patients with clinically active juvenile idiopathic arthritis (JIA), contrast-enhanced MRI shows no signs of synovitis. The objective of this study was to assess the frequency and the patient characteristics in clinically active JIA patients in which MRI showed no signs of synovitis. METHODS: From our cohort of 313 patients in which contrast-enhanced MRI of the knee had been performed, we selected 72 JIA patients with clinically active disease involving the target joint. The validated Juvenile Arthritis MRI Scoring (JAMRIS) system was used to evaluate synovial thickening. Patients were divided into two groups based on MRI outcome: Group 1: thickened synovium on MRI (JAMRIS score ≥1) or Group 2: normal synovium on MRI (JAMRIS score 0). Patient characteristics and disease activity parameters were then compared. RESULTS: In 35% (25/72) of these patients, MRI results contrasted with the clinical assessment (Group 2). In comparison to Group 1, the patients with discrepant findings were significantly older at the date of examination and JIA had been diagnosed at later age (median age of 13.2 vs. 10.9 and median age 10.0 vs. 8.0 respectively). In Group 2 there were significantly more patients with RF-negative polyarticular disease. CONCLUSION: Patients with RF-negative polyarticular JIA who had been diagnosed at a later age and were older at the time of MRI were most likely to be considered clinically active while MRI showed no signs of synovitis. These particular JIA patients may benefit from monitoring of disease activity by MRI to prevent overtreatment.

Imaging in juvenile idiopathic arthritis - international initiatives and ongoing work.

Imaging is increasingly being integrated into clinical practice to improve diagnosis, disease control and outcome in children with juvenile idiopathic arthritis. Over the last decades several international groups have been launched to standardize and validate different imaging techniques. To enhance transparency and facilitate collaboration, we present an overview of ongoing initiatives.

Juvenile idiopathic arthritis: magnetic resonance imaging of the clinically unaffected knee.

BACKGROUND: Synovial thickening detected on magnetic resonance imaging (MRI) is present in a significant number of children with clinically inactive juvenile idiopathic arthritis (JIA). OBJECTIVE: To evaluate patient characteristics and disease activity parameters in a cohort of children with clinically inactive JIA, both with and without synovial thickening, in order to clarify the observed discrepancy between clinical and MRI assessments. MATERIALS AND METHODS: We prospectively enrolled 52 clinically inactive JIA patients (median age 13.3 years, 63.5% girls) who underwent MRI of the knee as major target joint in JIA. Children were divided into two groups based on MRI outcome: group 1, with synovial thickening on MRI; and group 2, with no synovial thickening on MRI. We used the Juvenile Arthritis MRI Scoring system to evaluate synovial thickness. We compared patient characteristics and disease activity parameters between the groups. RESULTS: Synovial thickening on MRI was present in 18 clinically inactive patients (group 1, 34.6%). The age was significantly lower for the patients in group 1 (median 10.7 versus 14.4, P=0.008). No significant differences were observed in any of the other patient characteristics nor the disease activity parameters tested. CONCLUSION: Synovial thickening on MRI was present in nearly 35% of the children with clinically inactive JIA. Children with synovial thickening on MRI were significantly younger than those without. This might indicate that younger patients are at risk of subclinical disease activity and under-treatment, although the exact clinical relevance of synovial thickening on MRI has not been determined.

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

OBJECTIVES: To 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. METHODS: For 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. RESULTS: We 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). CONCLUSIONS: The 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.

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

OBJECTIVES: To compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA). METHODS: Regions 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. RESULTS: Thirty-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). CONCLUSIONS: Similar 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.

Determinants of clinical right ventricular failure after congenital heart surgery in adults.

OBJECTIVES: Right ventricular (RV) failure after cardiac surgery is a clinical entity with high morbidity and mortality. Patients with congenital heart disease (CHD) often undergo right-sided cardiac surgery. The authors aimed to identify determinants of RV failure after cardiac surgery to differentiate patients with increased risk. DESIGN: A retrospective chart review. SETTING: University hospital. PARTICIPANTS: Adults with CHD operated on between January 2001 and January 2011. INTERVENTIONS: Clinical characteristics, laboratory tests, surgical data, and intensive care unit outcome were obtained from medical records. MEASUREMENTS AND MAIN RESULTS: The diagnosis of clinical RV failure was made by careful review of the medical records by 2 independent physicians. Patients only were identified as having RV failure if (1) they had elevated jugular venous pressure, (2) they had impaired postoperative RV function on transthoracic echocardiography, and (3) a diagnosis of RV failure was documented clearly in the medical charts by the treating physician. Data of 412 consecutive patients (median age 36 [range 18-74] years, 56% male) were studied. Eighteen patients had clinical RV failure (4.4%) postoperatively, of whom 6 patients died. Patients undergoing left- and both-sided surgery had an equal risk of developing clinical RV failure as compared with patients undergoing right-sided surgery. In multivariate logistic regression analysis, preoperative impaired RV function, supraventricular tachycardia, and cardiopulmonary bypass time >150 minutes were the strongest determinants of clinical RV failure (p<0.05, for all). CONCLUSIONS: RV failure after cardiac surgery is a serious complication, and occurs regardless of the side of surgery. A tailored approach in patients with CHD at highest risk of RV failure should be considered.