Publications by authors named "Anouk M Barendregt"

17 Publications

  • Page 1 of 1

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

Pediatr Radiol 2020 09 13;50(10):1387-1396. Epub 2020 Jul 13.

Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Academic Medical Center Amsterdam Movement Sciences, University of Amsterdam, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1007/s00247-020-04739-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445206PMC
September 2020

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

Pediatr Rheumatol Online J 2020 Apr 15;18(1):33. Epub 2020 Apr 15.

Amsterdam UMC, Department Coronel Institute of Occupational Health. Amsterdam Public Health research institute, P.O. Box 22700, Amsterdam, DE, NL-1100, The Netherlands.

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.
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http://dx.doi.org/10.1186/s12969-020-00429-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158382PMC
April 2020

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

Radiology 2020 05 10;295(2):373-380. Epub 2020 Mar 10.

From the Department of Radiology and Nuclear Medicine (A.M.B., E.C.v.G., A.J.N., M.M., R.H.), Department of Pediatric Immunology, Rheumatology and Infectious Disease (A.M.B., E.C.v.G., D.S.M., A.N.S.a.R., J.M.v.d.B., T.W.K.), and Department of Pediatrics (C.M.N.), Amsterdam University Medical Centers, location AMC, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Department of Radiology, Lucas Center for Imaging, Stanford University, Stanford, Calif (V.M.); Department of Pediatric Rheumatology, Reade, Amsterdam, the Netherlands (K.M.D.); and Department of Pediatrics, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands (K.M.D.).

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
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http://dx.doi.org/10.1148/radiol.2020191685DOI Listing
May 2020

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

Rheumatology (Oxford) 2020 09;59(9):2392-2401

Department of Paediatric Immunology, Rheumatology and Infectious Disease, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam.

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.
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http://dx.doi.org/10.1093/rheumatology/kez590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449815PMC
September 2020

T-mapping for assessing knee joint cartilage in children with juvenile idiopathic arthritis - feasibility and repeatability.

Pediatr Radiol 2020 03 9;50(3):371-379. Epub 2019 Nov 9.

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, location AMC, Meibergdreef 9, Room G1-226, 1105 AZ, Amsterdam, The Netherlands.

Background: Ongoing arthritis in children with juvenile idiopathic arthritis (JIA) can result in cartilage damage.

Objective: To study the feasibility and repeatability of T for assessing knee cartilage in JIA and also to describe T values and study correlation between T and conventional MRI scores for disease activity.

Materials And Methods: Thirteen children with JIA or suspected JIA underwent 3-tesla (T) knee MRI that included conventional sequences and a T sequence. Segmentation of knee cartilage was carried out on T images. We used intraclass correlation coefficient to study the repeatability of segmentation in a subset of five children. We used the juvenile arthritis MRI scoring system to discriminate inflamed from non-inflamed knees. The Mann-Whitney U and Spearman correlation compared T between children with and without arthritis on MRI and correlated T with the juvenile arthritis MRI score.

Results: All children successfully completed the MRI examination. No images were excluded because of poor quality. Repeatability of T measurement had an intraclass correlation coefficient (ICC) of 0.99 (P<0.001). We observed no structural cartilage damage and found no differences in T between children with (n=7) and without (n=6) inflamed knees (37.8 ms vs. 31.7 ms, P=0.20). However, we observed a moderate correlation between T values and the juvenile arthritis MRI synovitis score (r=0.59, P=0.04).

Conclusion: This pilot study suggests that T is a feasible and repeatable quantitative imaging technique in children. T values were associated with the juvenile arthritis MRI synovitis score.
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http://dx.doi.org/10.1007/s00247-019-04557-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026305PMC
March 2020

Emerging quantitative MR imaging biomarkers in inflammatory arthritides.

Eur J Radiol 2019 Dec 19;121:108707. Epub 2019 Oct 19.

Amsterdam University Medical Centers, location AMC, Department of Radiology and Nuclear Medicine, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands; Amsterdam Movement Sciences Research Institute, Amsterdam University Medical Centers, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands; Department of Radiology, University College London Hospital, 235 Euston Rd, NW12BU, London, United Kingdom. Electronic address:

Purpose: To review quantitative magnetic resonance imaging (qMRI) methods for imaging inflammation in connective tissues and the skeleton in inflammatory arthritis. This review is designed for a broad audience including radiologists, imaging technologists, rheumatologists and other healthcare professionals.

Methods: We discuss the use of qMRI for imaging skeletal inflammation from both technical and clinical perspectives. We consider how qMRI can be targeted to specific aspects of the pathological process in synovium, cartilage, bone, tendons and entheses. Evidence for the various techniques from studies of both adults and children with inflammatory arthritis is reviewed and critically appraised.

Results: qMRI has the potential to objectively identify, characterize and quantify inflammation of the connective tissues and skeleton in both adult and pediatric patients. Measurements of tissue properties derived using qMRI methods can serve as imaging biomarkers, which are potentially more reproducible and informative than conventional MRI methods. Several qMRI methods are nearing transition into clinical practice and may inform diagnosis and treatment decisions, with the potential to improve patient outcomes.

Conclusions: qMRI enables specific assessment of inflammation in synovium, cartilage, bone, tendons and entheses, and can facilitate a more consistent, personalized approach to diagnosis, characterisation and monitoring of disease.
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http://dx.doi.org/10.1016/j.ejrad.2019.108707DOI Listing
December 2019

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

Pediatr Radiol 2019 05 1;49(5):638-645. Epub 2019 Feb 1.

Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1007/s00247-018-04332-xDOI Listing
May 2019

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.

Eur Radiol 2019 Jun;29(6):3319-3320

Department of Radiology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

The original version of this article, published on 12 June 2017, unfortunately contained a mistake.
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http://dx.doi.org/10.1007/s00330-018-5881-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828305PMC
June 2019

Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.

JAMA Pediatr 2018 10 1;172(10):e182293. Epub 2018 Oct 1.

Section of Paediatrics, Imperial College London, London, United Kingdom.

Importance: To date, there is no diagnostic test for Kawasaki disease (KD). Diagnosis is based on clinical features shared with other febrile conditions, frequently resulting in delayed or missed treatment and an increased risk of coronary artery aneurysms.

Objective: To identify a whole-blood gene expression signature that distinguishes children with KD in the first week of illness from other febrile conditions.

Design, Setting, And Participants: The case-control study comprised a discovery group that included a training and test set and a validation group of children with KD or comparator febrile illness. The setting was pediatric centers in the United Kingdom, Spain, the Netherlands, and the United States. The training and test discovery group comprised 404 children with infectious and inflammatory conditions (78 KD, 84 other inflammatory diseases, and 242 bacterial or viral infections) and 55 healthy controls. The independent validation group comprised 102 patients with KD, including 72 in the first 7 days of illness, and 130 febrile controls. The study dates were March 1, 2009, to November 14, 2013, and data analysis took place from January 1, 2015, to December 31, 2017.

Main Outcomes And Measures: Whole-blood gene expression was evaluated using microarrays, and minimal transcript sets distinguishing KD were identified using a novel variable selection method (parallel regularized regression model search). The ability of transcript signatures (implemented as disease risk scores) to discriminate KD cases from controls was assessed by area under the curve (AUC), sensitivity, and specificity at the optimal cut point according to the Youden index.

Results: Among 404 patients in the discovery set, there were 78 with KD (median age, 27 months; 55.1% male) and 326 febrile controls (median age, 37 months; 56.4% male). Among 202 patients in the validation set, there were 72 with KD (median age, 34 months; 62.5% male) and 130 febrile controls (median age, 17 months; 56.9% male). A 13-transcript signature identified in the discovery training set distinguished KD from other infectious and inflammatory conditions in the discovery test set, with AUC of 96.2% (95% CI, 92.5%-99.9%), sensitivity of 81.7% (95% CI, 60.0%-94.8%), and specificity of 92.1% (95% CI, 84.0%-97.0%). In the validation set, the signature distinguished KD from febrile controls, with AUC of 94.6% (95% CI, 91.3%-98.0%), sensitivity of 85.9% (95% CI, 76.8%-92.6%), and specificity of 89.1% (95% CI, 83.0%-93.7%). The signature was applied to clinically defined categories of definite, highly probable, and possible KD, resulting in AUCs of 98.1% (95% CI, 94.5%-100%), 96.3% (95% CI, 93.3%-99.4%), and 70.0% (95% CI, 53.4%-86.6%), respectively, mirroring certainty of clinical diagnosis.

Conclusions And Relevance: In this study, a 13-transcript blood gene expression signature distinguished KD from other febrile conditions. Diagnostic accuracy increased with certainty of clinical diagnosis. A test incorporating the 13-transcript disease risk score may enable earlier diagnosis and treatment of KD and reduce inappropriate treatment in those with other diagnoses.
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http://dx.doi.org/10.1001/jamapediatrics.2018.2293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233768PMC
October 2018

Imaging of the knee in juvenile idiopathic arthritis.

Pediatr Radiol 2018 06 8;48(6):818-827. Epub 2018 May 8.

Department of Radiology and Nuclear Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.

In juvenile idiopathic arthritis (JIA), imaging is increasingly used in clinical practice. In this paper we discuss imaging of the knee, the clinically most commonly affected joint in JIA. In the last decade, a number of important steps have been made in the development of imaging outcome measures in children with JIA knee involvement. Ultrasound is undergoing a fast validation process, which should be accomplished within the next few years. The validation processes of MRI as an imaging biomarker for clinical trials in the JIA knee are at an advanced stage, with important data available on the feasibility, reliability and validity of the Juvenile Arthritis MRI Scoring system. Moreover, both US and MRI data are emerging on the normal appearance of the growing knee joint.
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http://dx.doi.org/10.1007/s00247-017-4015-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954001PMC
June 2018

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

Eur J Radiol 2018 May 6;102:36-40. Epub 2018 Mar 6.

Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital AMC, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ejrad.2018.02.027DOI Listing
May 2018

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

Pediatr Radiol 2018 03 6;48(3):333-340. Epub 2018 Jan 6.

Department of Radiology and Nuclear Medicine, Academic Medical Center, University of Amsterdam, Department of Radiology (G1-213), Meibergdreef 9, 1105AZ, Amsterdam, the Netherlands.

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.
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http://dx.doi.org/10.1007/s00247-017-4059-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823947PMC
March 2018

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

Eur Radiol 2018 Mar 6;28(3):1167-1174. Epub 2017 Oct 6.

Department of Radiology and Nuclear Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1007/s00330-017-5067-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811591PMC
March 2018

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

Eur Radiol 2017 Nov 12;27(11):4889-4899. Epub 2017 Jun 12.

Department of Radiology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

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 × 10mm/s in MRI-active and 1.25 × 10mm/s in MRI-inactive JIA, p = 0.001, 95% confidence interval of difference in medians =0.11-0.53 × 10mm/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.
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http://dx.doi.org/10.1007/s00330-017-4876-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635098PMC
November 2017

Protein array autoantibody profiles to determine diagnostic markers for neuropsychiatric systemic lupus erythematosus.

Rheumatology (Oxford) 2017 08;56(8):1407-1416

Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital Academic Medical Center.

Objective: The aim was to investigate the association between autoantibodies (autoAbs) and neuropsychiatric (NP) involvement in patients with SLE and to evaluate whether any autoAb or a combination of these autoAbs could indicate the underlying pathogenic process.

Methods: Using a multiplexed protein array for 94 antigens, we compared the serum autoAb profiles of 69 NPSLE patients, 203 SLE patients without NP involvement (non-NPSLE) and 51 healthy controls. Furthermore, we compared the profiles of NPSLE patients with clinical inflammatory (n = 38) and ischaemic (n = 31) NP involvement.

Results: In total, 75 IgG and 47 IgM autoAbs were associated with SLE patients in comparison with healthy controls. Comparing NPSLE with non-NPSLE and healthy control sera, 9 IgG (amyloid, cardiolipin, glycoprotein 2, glycoprotein 210, heparin, heparan sulphate, histone H2A, prothrombin protein and vimentin) and 12 IgM (amyloid, cardiolipin, centromere protein A, collagen II, histones H2A and H2B, heparan sulphate, heparin, mitochondrial 2, nuclear Mi-2, nucleoporin 62 and vimentin) autoAbs were present at significantly different levels in NPSLE. The combination of IgG autoAbs against heparan sulphate, histone H2B and vimentin could differentiate NPSLE from non-NPSLE (area under the curve 0.845, 99.97% CI: 0.756, 0.933; P < 0.0001). Compared with non-NPSLE, four IgG and seven IgM autoAbs were significantly associated with inflammatory NPSLE. In ischaemic NPSLE, three IgG and three IgM autoAbs were significantly different from non-NPSLE patients.

Conclusion: In our cohort, the presence of high levels of anti-heparan sulphate and anti-histone H2B combined with low levels of anti-vimentin IgG autoAbs is highly suggestive of NPSLE. These results need to be validated in external cohorts.
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http://dx.doi.org/10.1093/rheumatology/kex073DOI Listing
August 2017

Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children.

JAMA 2016 Aug 23-30;316(8):835-45

Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom.

Importance: Because clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment, while bacterial infection is missed in others.

Objective: To identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children.

Design, Setting, And Participants: Febrile children presenting to participating hospitals in the United Kingdom, Spain, the Netherlands, and the United States between 2009-2013 were prospectively recruited, comprising a discovery group and validation group. Each group was classified after microbiological investigation as having definite bacterial infection, definite viral infection, or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were identified in the discovery group and diagnostic performance assessed in the validation group. Additional validation was undertaken in separate studies of children with meningococcal disease (n = 24) and inflammatory diseases (n = 48) and on published gene expression datasets.

Exposures: A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis.

Main Outcomes And Measures: Definite bacterial and viral infection was confirmed by culture or molecular detection of the pathogens. Performance of the RNA signature was evaluated in the definite bacterial and viral group and in the indeterminate infection group.

Results: The discovery group of 240 children (median age, 19 months; 62% male) included 52 with definite bacterial infection, of whom 36 (69%) required intensive care, and 92 with definite viral infection, of whom 32 (35%) required intensive care. Ninety-six children had indeterminate infection. Analysis of RNA expression data identified a 38-transcript signature distinguishing bacterial from viral infection. A smaller (2-transcript) signature (FAM89A and IFI44L) was identified by removing highly correlated transcripts. When this 2-transcript signature was implemented as a disease risk score in the validation group (130 children, with 23 definite bacterial, 28 definite viral, and 79 indeterminate infections; median age, 17 months; 57% male), all 23 patients with microbiologically confirmed definite bacterial infection were classified as bacterial (sensitivity, 100% [95% CI, 100%-100%]) and 27 of 28 patients with definite viral infection were classified as viral (specificity, 96.4% [95% CI, 89.3%-100%]). When applied to additional validation datasets from patients with meningococcal and inflammatory diseases, bacterial infection was identified with a sensitivity of 91.7% (95% CI, 79.2%-100%) and 90.0% (95% CI, 70.0%-100%), respectively, and with specificity of 96.0% (95% CI, 88.0%-100%) and 95.8% (95% CI, 89.6%-100%). Of the children in the indeterminate groups, 46.3% (63/136) were classified as having bacterial infection, although 94.9% (129/136) received antibiotic treatment.

Conclusions And Relevance: This study provides preliminary data regarding test accuracy of a 2-transcript host RNA signature discriminating bacterial from viral infection in febrile children. Further studies are needed in diverse groups of patients to assess accuracy and clinical utility of this test in different clinical settings.
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http://dx.doi.org/10.1001/jama.2016.11236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997174PMC
September 2016

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

Skeletal Radiol 2015 Dec 24;44(12):1805-11. Epub 2015 Jul 24.

Department of Radiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Objective: To 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 Methods: Standard magnetic resonance imaging of the knee including post-contrast imaging was obtained in eight patients (mean age, 12 years 8 months, 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.

Results: DWI 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, 1.92 × 10(-3) mm(2)/s vs. 2.40 × 10(-3) mm(2)/s, p = 0.006, respectively). Similar results were obtained when the two observers were analyzed separately (observer 1: p = 0.006, observer 2: p = 0.04).

Conclusions: In 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.
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http://dx.doi.org/10.1007/s00256-015-2208-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608988PMC
December 2015