{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:23:08Z","timestamp":1787959388659,"version":"build-2784847793"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2022LZY002"],"award-info":[{"award-number":["ZR2022LZY002"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2021QH230"],"award-info":[{"award-number":["ZR2021QH230"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["82205144"],"award-info":[{"award-number":["82205144"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>\nPurpose\n<\/jats:title>\n<jats:p>Ultrasound combined with Doppler techniques has been widely utilized to evaluate joint inflammation and internal structural changes in animal models of rheumatoid arthritis. However, previous assessments using these techniques were predominantly semi-quantitative, which may limit the precision and reliability of the results. Therefore, the primary objective of this study was to explore the potential advantages of three-dimensional (3D) volumetric ultrasound and color Doppler in quantitatively assessing the progression of disease.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>\nObjective\n<\/jats:title>\n<jats:p>To quantify the severity and progression of collagen-induced arthritis (CIA) mouse model using a micro-imaging tool, 3D volumetric ultrasound and color Doppler, and assess if 3D model-based volumetric changes of joint space and vascularity correlate with clinical, histological and bone destruction findings.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>\nMethods\n<\/jats:title>\n<jats:p>CIA was induced in mice on a DBA\/1J background at 7\u2009~\u20098 weeks of age. 3D volumetric ultrasound and color Doppler analysis was performed on knee and ankle joints of all mice using the Vevo 2100 system at 0, 2, 4, 8 weeks after the booster immunization. Clinical, histological and bone destruction analysis were performed as usual. Correlation analysis of the volumetric changes of joint space and vascularity with clinical, histological and bone destruction score were assessed via Spearman\u2019s test.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>\nResults\n<\/jats:title>\n<jats:p>It was possible to quantify the severity of joint inflammation and intra-articular changes during the progression of CIA by 3D volumetric ultrasound and color Doppler. The 3D model-based volumetric changes of joint space and vascularity have significant correlations with clinical, histological and bone destruction score of arthritis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>\nConclusions\n<\/jats:title>\n<jats:p>We demonstrated that 3D volumetric ultrasound and color Doppler is a noninvasive, quantitative tool for evaluating CIA mice in vivo. Despite certain limitations, those technology significantly enhance our ability to monitor disease progression and severity, assess therapeutic interventions, and reduce reliance on invasive techniques.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0321124","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T20:11:20Z","timestamp":1744056680000},"page":"e0321124","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["In vivo quantification of collagen-induced arthritis mouse model by three-dimensional volumetric ultrasound and color Doppler"],"prefix":"10.1371","volume":"20","author":[{"given":"Qingyun","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengteng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8427-6420","authenticated-orcid":true,"given":"Lisheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"issue":"10055","key":"pone.0321124.ref001","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"JS Smolen","year":"2016","journal-title":"Lancet"},{"issue":"5","key":"pone.0321124.ref002","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/annrheumdis-2012-203130","article-title":"What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? A systematic literature review","volume":"73","author":"JAB van Nies","year":"2014","journal-title":"Ann Rheum Dis"},{"issue":"12","key":"pone.0321124.ref003","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1136\/annrheumdis-2017-211585","article-title":"The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology","volume":"76","author":"I M\u00f6ller","year":"2017","journal-title":"Ann Rheum Dis"},{"issue":"11","key":"pone.0321124.ref004","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s11547-019-01002-2","article-title":"Ultrasound imaging in rheumatoid arthritis","volume":"124","author":"E Filippucci","year":"2019","journal-title":"Radiol Med"},{"issue":"10","key":"pone.0321124.ref005","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrrheum.2014.145","article-title":"Progress in imaging in rheumatology","volume":"10","author":"E Filippucci","year":"2014","journal-title":"Nat Rev Rheumatol"},{"issue":"1","key":"pone.0321124.ref006","doi-asserted-by":"crossref","first-page":"e000428","DOI":"10.1136\/rmdopen-2016-000428","article-title":"Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 1: definition and development of a standardised, consensus-based scoring system","volume":"3","author":"M-A D\u2019Agostino","year":"2017","journal-title":"RMD Open"},{"issue":"8","key":"pone.0321124.ref007","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s12325-018-0751-8","article-title":"Clinical, ultrasound, and predictability outcomes following certolizumab pegol treatment (with Methotrexate) in patients with moderate-to-severe rheumatoid arthritis: 52-week results from the CZP-SPEED study","volume":"35","author":"P Sarzi-Puttini","year":"2018","journal-title":"Adv Ther"},{"key":"pone.0321124.ref008","first-page":"vii36-42","article-title":"Imaging tools in rheumatoid arthritis: ultrasound vs magnetic resonance imaging","author":"YK Tan","year":"2012","journal-title":"Rheumatology (Oxford)"},{"issue":"1 Suppl 80","key":"pone.0321124.ref009","first-page":"S85-90","article-title":"Ultrasound versus conventional radiography in the assessment of bone erosions in rheumatoid arthritis","volume":"32","author":"F Salaffi","year":"2014","journal-title":"Clin Exp Rheumatol"},{"issue":"6","key":"pone.0321124.ref010","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.ultrasmedbio.2005.02.010","article-title":"Doppler sonography in assessing disease activity in rheumatoid arthritis","volume":"31","author":"K Varsamidis","year":"2005","journal-title":"Ultrasound Med Biol"},{"issue":"1","key":"pone.0321124.ref011","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/jcu.20175","article-title":"Power Doppler assessment of overall disease activity in patients with rheumatoid arthritis","volume":"34","author":"A Kiris","year":"2006","journal-title":"J Clin Ultrasound"},{"issue":"2","key":"pone.0321124.ref012","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00256-006-0196-z","article-title":"Ultrasound detects rapid progression of erosive disease in early rheumatoid arthritis: a prospective longitudinal study","volume":"36","author":"S Bajaj","year":"2007","journal-title":"Skeletal Radiol"},{"issue":"1","key":"pone.0321124.ref013","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/art.22461","article-title":"Longitudinal power Doppler ultrasonographic assessment of joint inflammatory activity in early rheumatoid arthritis: predictive value in disease activity and radiologic progression","volume":"57","author":"E Naredo","year":"2007","journal-title":"Arthritis Rheum"},{"issue":"12","key":"pone.0321124.ref014","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1136\/ard.2007.083915","article-title":"Ultrasound and Doppler micro-imaging in a model of rheumatoid arthritis in mice","volume":"67","author":"G Clavel","year":"2008","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"pone.0321124.ref015","first-page":"49","article-title":"Diagnostic sensitivity and specificity of Doppler ultrasound in rheumatoid arthritis","volume":"35","author":"L Terslev","year":"2008","journal-title":"J Rheumatol"},{"issue":"4","key":"pone.0321124.ref016","first-page":"300","article-title":"Gray scale and power Doppler ultrasonography in evaluation of early rheumatoid arthritis","volume":"12","author":"C Botar-Jid","year":"2010","journal-title":"Med Ultrason"},{"issue":"2","key":"pone.0321124.ref017","first-page":"637","article-title":"Power Doppler sonography, a non-invasive method of assessment of the synovial inflammation in patients with early rheumatoid arthritis","volume":"52","author":"F Vreju","year":"2011","journal-title":"Rom J Morphol Embryol"},{"issue":"2","key":"pone.0321124.ref018","first-page":"187","article-title":"Musculoskeletal ultrasonography in rheumatoid arthritis","volume":"22","author":"S Kawashiri","year":"2012","journal-title":"Clin Calcium"},{"issue":"2","key":"pone.0321124.ref019","first-page":"140","article-title":"Role of diagnostic ultrasound in assessment of disease activity in rheumatoid arthritis","volume":"59","author":"NL Zerjavi\u0107","year":"2012","journal-title":"Reumatizam"},{"issue":"11","key":"pone.0321124.ref020","first-page":"1020","article-title":"Role of ultrasonography in rheumatoid arthritis","volume":"46","author":"S Miladi","year":"2017","journal-title":"Presse Med"},{"issue":"1","key":"pone.0321124.ref021","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3899\/jrheum.141416","article-title":"Summary findings of a systematic literature review of the ultrasound assessment of bone erosions in rheumatoid arthritis","volume":"43","author":"M Szkudlarek","year":"2016","journal-title":"J Rheumatol"},{"issue":"2","key":"pone.0321124.ref022","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/art.10784","article-title":"Diagnostic value of high-resolution B-mode and doppler sonography for imaging of hand and finger joints in rheumatoid arthritis","volume":"48","author":"C Weidekamm","year":"2003","journal-title":"Arthritis Rheum"},{"issue":"6","key":"pone.0321124.ref023","doi-asserted-by":"crossref","first-page":"R119","DOI":"10.1186\/ar2327","article-title":"Ultrasonography, magnetic resonance imaging, radiography, and clinical assessment of inflammatory and destructive changes in fingers and toes of patients with psoriatic arthritis","volume":"9","author":"C Wiell","year":"2007","journal-title":"Arthritis Res Ther"},{"issue":"5","key":"pone.0321124.ref024","doi-asserted-by":"crossref","first-page":"502","DOI":"10.3109\/s10165-009-0190-0","article-title":"Screening for rheumatoid arthritis with finger joint power Doppler ultrasonography: quantification of conventional power Doppler ultrasonographic scoring","volume":"19","author":"J Fukae","year":"2009","journal-title":"Mod Rheumatol"},{"issue":"2","key":"pone.0321124.ref025","first-page":"68","article-title":"Diagnostic ultrasound of the small joints of the hands and feet: current status and role of ultrasound in early arthritis","volume":"57","author":"P Peri\u0107","year":"2010","journal-title":"Reumatizam"},{"issue":"8","key":"pone.0321124.ref026","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.ejrad.2010.01.005","article-title":"Colour Doppler ultrasonography evaluation of vascularization in the wrist and finger joints in rheumatoid arthritis patients and healthy subjects","volume":"81","author":"M Carotti","year":"2012","journal-title":"Eur J Radiol"},{"issue":"9","key":"pone.0321124.ref027","doi-asserted-by":"crossref","first-page":"e73766","DOI":"10.1371\/journal.pone.0073766","article-title":"Power Doppler ultrasound phenotyping of expanding versus collapsed popliteal lymph nodes in murine inflammatory arthritis","volume":"8","author":"EM Bouta","year":"2013","journal-title":"PLoS One"},{"issue":"4","key":"pone.0321124.ref028","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1002\/jbmr.2392","article-title":"Validation of power Doppler versus contrast-enhanced magnetic resonance imaging quantification of joint inflammation in murine inflammatory arthritis","volume":"30","author":"EM Bouta","year":"2015","journal-title":"J Bone Miner Res"},{"issue":"11","key":"pone.0321124.ref029","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1136\/ard.2007.076430","article-title":"Utility of animal models for identification of potential therapeutics for rheumatoid arthritis","volume":"67","author":"M Hegen","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"pone.0321124.ref030","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/978-1-60761-058-8_11","article-title":"Collagen-induced arthritis in mice","volume":"602","author":"L Bevaart","year":"2010","journal-title":"Methods Mol Biol"},{"issue":"5","key":"pone.0321124.ref031","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/nprot.2007.173","article-title":"Collagen-induced arthritis","volume":"2","author":"DD Brand","year":"2007","journal-title":"Nat Protoc"},{"key":"pone.0321124.ref032","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/978-1-59745-402-5_14","article-title":"Collagen-induced arthritis in mice","volume":"136","author":"RO Williams","year":"2007","journal-title":"Methods Mol Med"},{"key":"pone.0321124.ref033","first-page":"295","article-title":"The mouse model of collagen-induced arthritis","volume":"102","author":"DD Brand","year":"2004","journal-title":"Methods Mol Med"},{"issue":"5 Suppl 85","key":"pone.0321124.ref034","first-page":"S-13-6","article-title":"Optimising ultrasonography in rheumatology","volume":"32","author":"HI Keen","year":"2014","journal-title":"Clin Exp Rheumatol"},{"issue":"10","key":"pone.0321124.ref035","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1016\/j.ultrasmedbio.2017.06.009","article-title":"Freehand 3-D ultrasound imaging: a systematic review","volume":"43","author":"MH Mozaffari","year":"2017","journal-title":"Ultrasound Med Biol"},{"key":"pone.0321124.ref036","doi-asserted-by":"crossref","first-page":"106494","DOI":"10.1016\/j.intimp.2020.106494","article-title":"CXCR3 antagonist AMG487 inhibits glucocorticoid-induced tumor necrosis factor-receptor-related protein and inflammatory mediators in CD45 expressing cells in collagen-induced arthritis mouse model","volume":"84","author":"SA Bakheet","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"pone.0321124.ref037","doi-asserted-by":"crossref","first-page":"109395","DOI":"10.1016\/j.cellsig.2019.109395","article-title":"CXCR3 antagonist AMG487 suppresses rheumatoid arthritis pathogenesis and progression by shifting the Th17\/Treg cell balance","volume":"64","author":"SA Bakheet","year":"2019","journal-title":"Cell Signal"},{"key":"pone.0321124.ref038","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fphar.2020.00045","article-title":"Alleviation of synovial inflammation of juanbi-tang on collagen-induced arthritis and TNF-Tg mice model","volume":"11","author":"T Wang","year":"2020","journal-title":"Front Pharmacol"},{"key":"pone.0321124.ref039","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fphar.2019.00094","article-title":"Astragalin suppresses inflammatory responses and bone destruction in mice with collagen-induced arthritis and in human fibroblast-like synoviocytes","volume":"10","author":"Q Jia","year":"2019","journal-title":"Front Pharmacol"},{"issue":"1","key":"pone.0321124.ref040","first-page":"79","article-title":"Three-dimensional volumetric ultrasonography. Does it improve reliabililty of musculoskeletal ultrasound?","volume":"28","author":"E Naredo","year":"2010","journal-title":"Clin Exp Rheumatol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0321124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T20:12:17Z","timestamp":1744056737000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0321124"}},"subtitle":[],"editor":[{"given":"Fulvio","family":"D'Acquisto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,7]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0321124","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,7]]}}}