{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:26:18Z","timestamp":1791973578588,"version":"4.4.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T00:00:00Z","timestamp":1497225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T00:00:00Z","timestamp":1497225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003180","name":"Academic Medical Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003180","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objectives<\/jats:title>\n            <jats:p>To compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>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\u2019s rank was used to analyse the correlation between DCE and DWI.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>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 \u00d7 10<jats:sup>-3<\/jats:sup>mm<jats:sup>2<\/jats:sup>\/s in MRI-active and 1.25 \u00d7 10<jats:sup>-3<\/jats:sup>mm<jats:sup>2<\/jats:sup>\/s in MRI-inactive JIA, <jats:italic>p<\/jats:italic> = 0.001, 95% confidence interval of difference in medians =0.11-0.53 \u00d7 10<jats:sup>-3<\/jats:sup>mm<jats:sup>2<\/jats:sup>\/s. ADC correlated to ME, MIS and TIC 5 shapes (<jats:italic>r<\/jats:italic> = 0.62, <jats:italic>r<\/jats:italic> = 0.45, <jats:italic>r<\/jats:italic> = -0.51, respectively, all <jats:italic>p<\/jats:italic> &lt; 0.05).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:italic>Key Points<\/jats:italic>\n            <\/jats:title>\n            <jats:p>\u2022 <jats:italic>MRI can quantify: dynamic contrast<\/jats:italic>-<jats:italic>enhanced and diffusion<\/jats:italic>-<jats:italic>weighted MRI can quantify synovitis<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\u2022 <jats:italic>Both DWI and DCE can differentiate active from inactive JIA<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\u2022 <jats:italic>The DWI<\/jats:italic>-<jats:italic>derived apparent diffusion coefficient<\/jats:italic> (<jats:italic>ADC<\/jats:italic>) <jats:italic>is higher in active JIA<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\u2022 <jats:italic>DWI is non<\/jats:italic>-<jats:italic>invasive and thus safer and more patient<\/jats:italic>-<jats:italic>friendly<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\u2022 <jats:italic>DWI is a potentially powerful and non<\/jats:italic>-<jats:italic>invasive imaging biomarker for JIA<\/jats:italic>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00330-017-4876-y","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T15:27:13Z","timestamp":1497281233000},"page":"4889-4899","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis: a promising imaging biomarker as an alternative to gadolinium-based contrast agents"],"prefix":"10.1007","volume":"27","author":[{"given":"Anouk M.","family":"Barendregt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Charlotte","family":"van Gulik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Lavini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte M.","family":"Nusman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Merlijn","family":"van den Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieneke","family":"Schonenberg-Meinema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koert M.","family":"Dolman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taco W.","family":"Kuijpers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hemke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Maas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,12]]},"reference":[{"key":"4876_CR1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3899\/jrheum.141276","volume":"43","author":"CM Nusman","year":"2016","unstructured":"Nusman CM, Ording Muller LS, Hemke R et al (2016) 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. J Rheumatol 43:239\u2013244","journal-title":"J Rheumatol"},{"key":"4876_CR2","doi-asserted-by":"publisher","first-page":"354","DOI":"10.3899\/jrheum.131081","volume":"41","author":"R Hemke","year":"2014","unstructured":"Hemke R, Doria AS, Tzaribachev N, Maas M, van der Heijde DM, van Rossum MA (2014) Selecting magnetic resonance imaging (MRI) outcome measures for juvenile idiopathic arthritis (JIA) clinical trials: first report of the MRI in JIA special interest group. J Rheumatol 41:354\u2013358","journal-title":"J Rheumatol"},{"key":"4876_CR3","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1148\/rg.335125178","volume":"33","author":"EF Sheybani","year":"2013","unstructured":"Sheybani EF, Khanna G, White AJ, Demertzis JL (2013) Imaging of juvenile idiopathic arthritis: a multimodality approach. Radiographics 33:1253\u20131273","journal-title":"Radiographics"},{"key":"4876_CR4","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/S0140-6736(07)60363-8","volume":"369","author":"A Ravelli","year":"2007","unstructured":"Ravelli A, Martini A (2007) Juvenile idiopathic arthritis. Lancet 369:767\u2013778","journal-title":"Lancet"},{"key":"4876_CR5","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nrrheum.2012.30","volume":"8","author":"S Magni-Manzoni","year":"2012","unstructured":"Magni-Manzoni S, Malattia C, Lanni S, Ravelli A (2012) Advances and challenges in imaging in juvenile idiopathic arthritis. Nat Rev Rheumatol 8:329\u2013336","journal-title":"Nat Rev Rheumatol"},{"key":"4876_CR6","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1007\/s00330-014-3522-1","volume":"25","author":"W Stomp","year":"2015","unstructured":"Stomp W, Krabben A, van der Heijde D et al (2015) Aiming for a simpler early arthritis MRI protocol: can Gd contrast administration be eliminated? Eur Radiol 25:1520\u20131527","journal-title":"Eur Radiol"},{"key":"4876_CR7","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1007\/s00330-012-2684-y","volume":"23","author":"R Hemke","year":"2013","unstructured":"Hemke R, van Rossum MA, van Veenendaal M et al (2013) Reliability and responsiveness of the Juvenile Arthritis MRI Scoring (JAMRIS) system for the knee. Eur Radiol 23:1075\u20131083","journal-title":"Eur Radiol"},{"key":"4876_CR8","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1002\/art.1780391013","volume":"39","author":"AA Grom","year":"1996","unstructured":"Grom AA, Murray KJ, Luyrink L et al (1996) Patterns of expression of tumor necrosis factor alpha, tumor necrosis factor beta, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy. Arthritis Rheum 39:1703\u20131710","journal-title":"Arthritis Rheum"},{"key":"4876_CR9","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1093\/rheumatology\/keh250","volume":"43","author":"M Gattorno","year":"2004","unstructured":"Gattorno M, Gregorio A, Ferlito F et al (2004) Synovial expression of osteopontin correlates with angiogenesis in juvenile idiopathic arthritis. Rheumatology (Oxford) 43:1091\u20131096","journal-title":"Rheumatology (Oxford)"},{"key":"4876_CR10","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1007\/s00330-014-3168-z","volume":"24","author":"R Hemke","year":"2014","unstructured":"Hemke R, Lavini C, Nusman CM et al (2014) Pixel-by-pixel analysis of DCE-MRI curve shape patterns in knees of active and inactive juvenile idiopathic arthritis patients. Eur Radiol 24:1686\u20131693","journal-title":"Eur Radiol"},{"key":"4876_CR11","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/rheumatology\/kep343","volume":"49","author":"C Malattia","year":"2010","unstructured":"Malattia C, Damasio MB, Basso C et al (2010) Dynamic contrast-enhanced magnetic resonance imaging in the assessment of disease activity in patients with juvenile idiopathic arthritis. Rheumatology (Oxford) 49:178\u2013185","journal-title":"Rheumatology (Oxford)"},{"key":"4876_CR12","doi-asserted-by":"publisher","first-page":"89","DOI":"10.3109\/03009742.2011.608375","volume":"41","author":"MB Axelsen","year":"2012","unstructured":"Axelsen MB, Stoltenberg M, Poggenborg RP et al (2012) Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology. Scand J Rheumatol 41:89\u201394","journal-title":"Scand J Rheumatol"},{"key":"4876_CR13","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1002\/art.1780370807","volume":"37","author":"K Tamai","year":"1994","unstructured":"Tamai K, Yamato M, Yamaguchi T, Ohno W (1994) Dynamic magnetic resonance imaging for the evaluation of synovitis in patients with rheumatoid arthritis. Arthritis Rheum 37:1151\u20131157","journal-title":"Arthritis Rheum"},{"key":"4876_CR14","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1093\/rheumatology\/kes011","volume":"51","author":"MG van de Sande","year":"2012","unstructured":"van de Sande MG, van der Leij C, Lavini C, Wijbrandts CA, Maas M, Tak PP (2012) Characteristics of synovial inflammation in early arthritis analysed by pixel-by-pixel time-intensity curve shape analysis. Rheumatology (Oxford) 51:1240\u20131245","journal-title":"Rheumatology (Oxford)"},{"key":"4876_CR15","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1148\/radiol.2531081722","volume":"253","author":"C van der Leij","year":"2009","unstructured":"van der Leij C, van de Sande MG, Lavini C, Tak PP, Maas M (2009) Rheumatoid synovial inflammation: pixel-by-pixel dynamic contrast-enhanced MR imaging time-intensity curve shape analysis\u2014a feasibility study. Radiology 253:234\u2013240","journal-title":"Radiology"},{"key":"4876_CR16","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1002\/jmri.22786","volume":"35","author":"S Bonekamp","year":"2012","unstructured":"Bonekamp S, Corona-Villalobos CP, Kamel IR (2012) Oncologic applications of diffusion-weighted MRI in the body. J Magn Reson Imaging 35:257\u2013279","journal-title":"J Magn Reson Imaging"},{"key":"4876_CR17","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1546-0096-10-20","volume":"10","author":"H Neubauer","year":"2012","unstructured":"Neubauer H, Evangelista L, Morbach H et al (2012) Diffusion-weighted MRI of bone marrow oedema, soft tissue oedema and synovitis in paediatric patients: feasibility and initial experience. Pediatr Rheumatol Online J 10:20","journal-title":"Pediatr Rheumatol Online J"},{"key":"4876_CR18","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1007\/s00256-015-2208-3","volume":"44","author":"AM Barendregt","year":"2015","unstructured":"Barendregt AM, Nusman CM, Hemke R et al (2015) Feasibility of diffusion-weighted magnetic resonance imaging in patients with juvenile idiopathic arthritis on 1.0-T open-bore MRI. Skeletal Radiol 44:1805\u20131811","journal-title":"Skeletal Radiol"},{"issue":"5","key":"4876_CR19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/RLI.0000000000000273","volume":"51","author":"VM Runge","year":"2016","unstructured":"Runge VM (2016) Safety of the gadolinium-based contrast agents for magnetic resonance imaging, focusing in part on their accumulation in the brain and especially the dentate nucleus. Invest Radiol 51(5):273\u2013279","journal-title":"Invest Radiol"},{"key":"4876_CR20","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1148\/radiol.13131669","volume":"270","author":"T Kanda","year":"2014","unstructured":"Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2014) High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology 270:834\u2013841","journal-title":"Radiology"},{"key":"4876_CR21","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1007\/s00247-016-3646-3","volume":"46","author":"HH Hu","year":"2016","unstructured":"Hu HH, Pokorney A, Towbin RB, Miller JH (2016) Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams. Pediatr Radiol 46:1590\u20131598","journal-title":"Pediatr Radiol"},{"key":"4876_CR22","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1007\/s00330-016-4418-z","volume":"27","author":"ML Kromrey","year":"2017","unstructured":"Kromrey ML, Liedtke KR, Ittermann T et al (2017) Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years. Eur Radiol 27:772\u2013777","journal-title":"Eur Radiol"},{"issue":"26","key":"4876_CR23","doi-asserted-by":"publisher","first-page":"4577","DOI":"10.1007\/s00330-016-4245-2","volume":"2016","author":"E Tedeschi","year":"2016","unstructured":"Tedeschi E, Palma G, Canna A et al (2016) In vivo dentate nucleus MRI relaxometry correlates with previous administration of gadolinium-based contrast agents. Eur Radiol 2016(26):4577\u20134584","journal-title":"Eur Radiol"},{"key":"4876_CR24","first-page":"390","volume":"31","author":"RE Petty","year":"2004","unstructured":"Petty RE, Southwood TR, Manners P et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390\u2013392","journal-title":"J Rheumatol"},{"key":"4876_CR25","unstructured":"Lavini C, Maas M (2008) DCE-MRI analysis package comprising pixel-by-pixel classification of time intensity curves shapes, permeability maps and Gd concentration calculation. Magn Res Materials in Physics Biology and Medicine. 21(S1:486)"},{"key":"4876_CR26","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.mri.2006.10.021","volume":"25","author":"C Lavini","year":"2007","unstructured":"Lavini C, de Jonge MC, van de Sande MG, Tak PP, Nederveen AJ, Maas M (2007) Pixel-by-pixel analysis of DCE MRI curve patterns and an illustration of its application to the imaging of the musculoskeletal system. Magn Reson Imaging 25:604\u2013612","journal-title":"Magn Reson Imaging"},{"key":"4876_CR27","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1007\/s00330-015-3912-z","volume":"26","author":"CM Nusman","year":"2016","unstructured":"Nusman CM, Hemke R, Benninga MA et al (2016) Contrast-enhanced MRI of the knee in children unaffected by clinical arthritis compared to clinically active juvenile idiopathic arthritis patients. Eur Radiol 26:1141\u20131148","journal-title":"Eur Radiol"},{"key":"4876_CR28","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.berh.2013.03.006","volume":"27","author":"DM Gerlag","year":"2013","unstructured":"Gerlag DM, Tak PP (2013) How to perform and analyse synovial biopsies. Best Pract Res Clin Rheumatol 27:195\u2013207","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"4876_CR29","doi-asserted-by":"publisher","first-page":"20160027","DOI":"10.1259\/bjr.20160027","volume":"89","author":"C Neeley","year":"2016","unstructured":"Neeley C, Moritz M, Brown JJ, Zhou Y (2016) Acute side effects of three commonly used gadolinium contrast agents in the pediatric population. Br J Radiol 89:20160027","journal-title":"Br J Radiol"},{"key":"4876_CR30","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1007\/s00467-013-2636-z","volume":"29","author":"A Weller","year":"2014","unstructured":"Weller A, Barber JL, Olsen OE (2014) Gadolinium and nephrogenic systemic fibrosis: an update. Pediatr Nephrol 29:1927\u20131937","journal-title":"Pediatr Nephrol"},{"key":"4876_CR31","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/jmri.25196","volume":"44","author":"B Taouli","year":"2016","unstructured":"Taouli B, Beer AJ, Chenevert T et al (2016) Diffusion-weighted imaging outside the brain: consensus statement from an ISMRM-sponsored workshop. J Magn Reson Imaging 44:521\u2013540","journal-title":"J Magn Reson Imaging"},{"key":"4876_CR32","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.ejrad.2008.01.023","volume":"66","author":"MF Bellin","year":"2008","unstructured":"Bellin MF, Van Der Molen AJ (2008) Extracellular gadolinium-based contrast media: an overview. Eur J Radiol 66:160\u2013167","journal-title":"Eur J Radiol"}],"updated-by":[{"DOI":"10.1007\/s00330-018-5881-5","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T00:00:00Z","timestamp":1543536000000}}],"container-title":["European Radiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00330-017-4876-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-017-4876-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-017-4876-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T08:52:29Z","timestamp":1600332749000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00330-017-4876-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,12]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["4876"],"URL":"https:\/\/doi.org\/10.1007\/s00330-017-4876-y","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s00330-018-5881-5","asserted-by":"object"}]},"ISSN":["0938-7994","1432-1084"],"issn-type":[{"value":"0938-7994","type":"print"},{"value":"1432-1084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,12]]},"assertion":[{"value":"21 September 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2017","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2017","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2018","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original version of this article, published on 12 June 2017, unfortunately contained a mistake.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The scientific guarantor of this publication is Prof. Dr. Mario Maas.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Guarantor"}},{"value":"The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study has received funding by the Academic Medical Center through an MD\/PhD scholarship, awarded to AMB.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"No complex statistical methods were necessary for this paper.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Institutional Review Board approval was obtained.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all subjects (patients) in this study.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}