{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:35:38Z","timestamp":1790782538996,"version":"4.1.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T00:00:00Z","timestamp":1509667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T00:00:00Z","timestamp":1509667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>By using our dual-modality system enabling simultaneous real-time ultrasound (US) and photoacoustic (PA) imaging of human peripheral joints, we explored the potential contribution of PA imaging modality to rheumatology clinic. By performing PA imaging at a single laser wavelength, the spatially distributed hemoglobin content reflecting the hyperemia in synovial tissue in metacarpophalangeal (MCP) joints of 16 patients were imaged, and compared to the results from 16 healthy controls. In addition, by performing PA imaging at two laser wavelengths, the spatially distributed hemoglobin oxygenation reflecting the hypoxia in inflammatory joints of 10 patients were imaged, and compared to the results from 10 healthy controls. The statistical analyses of the PA imaging results demonstrated significant differences (p\u2009&lt;\u20090.001) in quantified hemoglobin content and oxygenation between the unequivocally arthritic joints and the normal joints. Increased hyperemia and increased hypoxia, two important physiological biomarkers of synovitis reflecting the increased metabolic demand and the relatively inadequate oxygen delivery in affected synovium, can both be objectively and non-invasively evaluated by PA imaging. The proposed dual-modality system has the potential of providing additional diagnostic information over the traditional US imaging approaches and introducing novel imaging biomarkers for diagnosis and treatment evaluation of inflammatory arthritis.<\/jats:p>","DOI":"10.1038\/s41598-017-15147-5","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T10:57:20Z","timestamp":1509361040000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["A Functional Study of Human Inflammatory Arthritis Using Photoacoustic Imaging"],"prefix":"10.1038","volume":"7","author":[{"given":"Janggun","family":"Jo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April","family":"Marquardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheeja","family":"Francis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish","family":"Gandikota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueding","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,3]]},"reference":[{"key":"15147_CR1","unstructured":"Centers for Disease, C. & Prevention. Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation\u2013United States, 2010-2012. MMWR. Morbidity and mortality weekly report \n                           62, 869-873 (2013)."},{"key":"15147_CR2","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nrrheum.2011.205","volume":"8","author":"S Konisti","year":"2012","unstructured":"Konisti, S., Kiriakidis, S. & Paleolog, E. M. Hypoxia\u2013a key regulator of angiogenesis and inflammation in rheumatoid arthritis. Nat Rev Rheumatol \n                           8, 153\u2013162, https:\/\/doi.org\/10.1038\/nrrheum.2011.205 (2012).","journal-title":"Nat Rev Rheumatol"},{"key":"15147_CR3","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1136\/annrheumdis-2015-208476","volume":"75","author":"M Biniecka","year":"2016","unstructured":"Biniecka, M. et al. Dysregulated bioenergetics: a key regulator of joint inflammation. Ann Rheum Dis \n                           75, 2192\u20132200, https:\/\/doi.org\/10.1136\/annrheumdis-2015-208476 (2016).","journal-title":"Ann Rheum Dis"},{"key":"15147_CR4","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12929-016-0281-0","volume":"23","author":"CM Quinonez-Flores","year":"2016","unstructured":"Quinonez-Flores, C. M., Gonzalez-Chavez, S. A. & Pacheco-Tena, C. Hypoxia and its implications in rheumatoid arthritis. J Biomed Sci \n                           23, 62, https:\/\/doi.org\/10.1186\/s12929-016-0281-0 (2016).","journal-title":"J Biomed Sci"},{"key":"15147_CR5","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1002\/eji.201444908","volume":"45","author":"SY Park","year":"2015","unstructured":"Park, S. Y. et al. HMGB1 induces angiogenesis in rheumatoid arthritis via HIF-1alpha activation. Eur J Immunol \n                           45, 1216\u20131227, https:\/\/doi.org\/10.1002\/eji.201444908 (2015).","journal-title":"Eur J Immunol"},{"key":"15147_CR6","doi-asserted-by":"publisher","first-page":"2766","DOI":"10.1007\/s00330-014-3331-6","volume":"24","author":"OC Nasui","year":"2014","unstructured":"Nasui, O. C. et al. Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla. Eur Radiol \n                           24, 2766\u20132778 (2014).","journal-title":"Eur Radiol"},{"key":"15147_CR7","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1007\/s00247-013-2844-5","volume":"44","author":"MW Chan","year":"2014","unstructured":"Chan, M. W. et al. Systematic protocol for assessment of the validity of BOLD MRI in a rabbit model of inflammatory arthritis at 1.5 tesla. Pediatr Radiol \n                           44, 566\u2013575, https:\/\/doi.org\/10.1007\/s00247-013-2844-5 (2014).","journal-title":"Pediatr Radiol"},{"key":"15147_CR8","unstructured":"Weissman, B. N. W. 1 online resource (xix, 749 pages) (Mosby\/Elsevier,, Philadelphia, PA, 2009)."},{"key":"15147_CR9","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/ncprheum0377","volume":"3","author":"WA Schmidt","year":"2007","unstructured":"Schmidt, W. A. Technology Insight: the role of color and power Doppler ultrasonography in rheumatology. Nature clinical practice Rheumatology \n                           3, 35\u201342 (2007). quiz 59.","journal-title":"Nature clinical practice Rheumatology"},{"key":"15147_CR10","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1136\/ard.60.7.690","volume":"60","author":"E Qvistgaard","year":"2001","unstructured":"Qvistgaard, E. et al. Quantitative ultrasonography in rheumatoid arthritis: evaluation of inflammation by Doppler technique. Ann Rheum Dis \n                           60, 690\u2013693 (2001).","journal-title":"Ann Rheum Dis"},{"key":"15147_CR11","doi-asserted-by":"publisher","first-page":"83","DOI":"10.2147\/RMI.S32950","volume":"6","author":"E Filippucci","year":"2013","unstructured":"Filippucci, E., Salaffi, F., Carotti, M. & Grassi, W. Doppler ultrasound imaging techniques for assessment of synovial inflammation. RMI 2013 \n                           6, 83\u201391, https:\/\/doi.org\/10.2147\/RMI.S32950 (2013).","journal-title":"RMI 2013"},{"key":"15147_CR12","doi-asserted-by":"publisher","first-page":"751","DOI":"10.3109\/17453676908989539","volume":"40","author":"I Goldie","year":"1969","unstructured":"Goldie, I. The synovial microvascular derangement in rheumatoid arthritis and osteoarthritis. Acta orthopaedica Scandinavica \n                           40, 751\u2013764 (1969).","journal-title":"Acta orthopaedica Scandinavica"},{"key":"15147_CR13","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1148\/radiographics.17.2.9084086","volume":"17","author":"UM Hamper","year":"1997","unstructured":"Hamper, U. M., DeJong, M. R., Caskey, C. I. & Sheth, S. Power Doppler imaging: clinical experience and correlation with color Doppler US and other imaging modalities. RadioGraphics \n                           17, 499\u2013513, https:\/\/doi.org\/10.1148\/radiographics.17.2.9084086 (1997).","journal-title":"RadioGraphics"},{"key":"15147_CR14","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1148\/radiology.190.3.8115639","volume":"190","author":"JM Rubin","year":"1994","unstructured":"Rubin, J. M., Bude, R. O., Carson, P. L., Bree, R. L. & Adler, R. S. Power Doppler US: a potentially useful alternative to mean frequency-based color Doppler US. Radiology \n                           190, 853\u2013856, https:\/\/doi.org\/10.1148\/radiology.190.3.8115639 (1994).","journal-title":"Radiology"},{"key":"15147_CR15","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1136\/ard.2004.024224","volume":"64","author":"AK Scheel","year":"2005","unstructured":"Scheel, A. K. et al. First clinical evaluation of sagittal laser optical tomography for detection of synovitis in arthritic finger joints. Ann Rheum Dis \n                           64, 239\u2013245, https:\/\/doi.org\/10.1136\/ard.2004.024224 (2005).","journal-title":"Ann Rheum Dis"},{"key":"15147_CR16","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1364\/OE.8.000447","volume":"8","author":"Y Xu","year":"2001","unstructured":"Xu, Y., Iftimia, N., Jiang, H., Key, L. & Bolster, M. Imaging of in vitro and in vivo bones and joints with continuous-wave diffuse optical tomography. Opt. Express \n                           8, 447\u2013451, https:\/\/doi.org\/10.1364\/oe.8.000447 (2001).","journal-title":"Opt. Express"},{"key":"15147_CR17","doi-asserted-by":"publisher","first-page":"055302","DOI":"10.1088\/2040-8978\/15\/5\/055302","volume":"15","author":"S Yao","year":"2013","unstructured":"Yao, S., Eric, S. & Huabei, J. Noninvasive imaging of hemoglobin concentration and oxygen saturation for detection of osteoarthritis in the finger joints using multispectral three-dimensional quantitative photoacoustic tomography. Journal of Optics \n                           15, 055302 (2013).","journal-title":"Journal of Optics"},{"key":"15147_CR18","doi-asserted-by":"publisher","first-page":"052001-052001","DOI":"10.1117\/1.2798757","volume":"12","author":"JM Lasker","year":"2007","unstructured":"Lasker, J. M., Fong, C. J., Ginat, D. T., Dwyer, E. & Hielscher, A. H. Dynamic optical imaging of vascular and metabolic reactivity in rheumatoid joints. Journal of biomedical optics \n                           12, 052001-052001\u2013052013, https:\/\/doi.org\/10.1117\/1.2798757 (2007).","journal-title":"Journal of biomedical optics"},{"key":"15147_CR19","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1148\/radiol.14132128","volume":"272","author":"P Mohajerani","year":"2014","unstructured":"Mohajerani, P. et al. Fluorescence-aided tomographic imaging of synovitis in the human finger. Radiology \n                           272, 865\u2013874 (2014).","journal-title":"Radiology"},{"key":"15147_CR20","doi-asserted-by":"publisher","unstructured":"Xu, M. H. & Wang, L. H. V. Photoacoustic imaging in biomedicine. Review of Scientific Instruments 77, https:\/\/doi.org\/10.1063\/1.2195024 (2006).","DOI":"10.1063\/1.2195024"},{"key":"15147_CR21","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1038\/nbt839","volume":"21","author":"X Wang","year":"2003","unstructured":"Wang, X. et al. Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain. Nature biotechnology \n                           21, 803\u2013806 (2003).","journal-title":"Nature biotechnology"},{"key":"15147_CR22","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nphoton.2009.157","volume":"3","author":"LV Wang","year":"2009","unstructured":"Wang, L. V. Multiscale photoacoustic microscopy and computed tomography. Nature photonics \n                           3, 503\u2013509 (2009).","journal-title":"Nature photonics"},{"key":"15147_CR23","doi-asserted-by":"publisher","first-page":"86001","DOI":"10.1117\/1.JBO.18.8.086001","volume":"18","author":"J Yuan","year":"2013","unstructured":"Yuan, J. et al. Real-time photoacoustic and ultrasound dual-modality imaging system facilitated with graphics processing unit and code parallel optimization. Journal of Biomedical Optics \n                           18, 86001\u201386001 (2013).","journal-title":"Journal of Biomedical Optics"},{"key":"15147_CR24","doi-asserted-by":"publisher","first-page":"n\/a","DOI":"10.1002\/wnan.1404","volume":"9","author":"JE Lemaster","year":"2017","unstructured":"Lemaster, J. E. & Jokerst, J. V. What is new in nanoparticle-based photoacoustic imaging? Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology \n                           9, n\/a\u2013n\/a, https:\/\/doi.org\/10.1002\/wnan.1404 (2017).","journal-title":"Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology"},{"key":"15147_CR25","doi-asserted-by":"publisher","first-page":"016706","DOI":"10.1103\/PhysRevE.71.016706","volume":"71","author":"M Xu","year":"2005","unstructured":"Xu, M. & Wang, L. V. Universal back-projection algorithm for photoacoustic computed tomography. Physical Review E \n                           71, 016706 (2005).","journal-title":"Physical Review E"},{"key":"15147_CR26","doi-asserted-by":"publisher","first-page":"3002","DOI":"10.1364\/OL.32.003002","volume":"32","author":"X Wang","year":"2007","unstructured":"Wang, X., Chamberland, D. L. & Jamadar, D. A. Noninvasive photoacoustic tomography of human peripheral joints toward diagnosis of inflammatory arthritis. Optics letters \n                           32, 3002\u20133004 (2007).","journal-title":"Optics letters"},{"key":"15147_CR27","doi-asserted-by":"publisher","first-page":"064002","DOI":"10.1117\/1.3257246","volume":"14","author":"Y Sun","year":"2009","unstructured":"Sun, Y., Sobel, E. & Jiang, H. Quantitative three-dimensional photoacoustic tomography of the finger joints: an in vivo study. Journal of biomedical optics \n                           14, 064002, https:\/\/doi.org\/10.1117\/1.3257246 (2009).","journal-title":"Journal of biomedical optics"},{"key":"15147_CR28","doi-asserted-by":"publisher","first-page":"10502","DOI":"10.1117\/1.JBO.18.1.010502","volume":"18","author":"G Xu","year":"2013","unstructured":"Xu, G. et al. Photoacoustic and ultrasound dual-modality imaging of human peripheral joints. Journal of biomedical optics \n                           18, 10502, https:\/\/doi.org\/10.1117\/1.JBO.18.1.010502 (2013).","journal-title":"Journal of biomedical optics"},{"key":"15147_CR29","doi-asserted-by":"publisher","first-page":"060501","DOI":"10.1117\/1.JBO.19.6.060501","volume":"19","author":"P van Es","year":"2014","unstructured":"van Es, P., Biswas, S. K., Moens, H. J. B., Steenbergen, W. & Manohar, S. Initial results of finger imaging using photoacoustic computed tomography. Journal of biomedical optics \n                           19, 060501\u2013060501, https:\/\/doi.org\/10.1117\/1.JBO.19.6.060501 (2014).","journal-title":"Journal of biomedical optics"},{"key":"15147_CR30","doi-asserted-by":"publisher","first-page":"96013","DOI":"10.1117\/1.JBO.17.9.096013","volume":"17","author":"JR Rajian","year":"2012","unstructured":"Rajian, J. R., Girish, G. & Wang, X. Photoacoustic tomography to identify inflammatory arthritis. Journal of biomedical optics \n                           17, 96013\u201396011, https:\/\/doi.org\/10.1117\/1.JBO.17.9.096013 (2012).","journal-title":"Journal of biomedical optics"},{"key":"15147_CR31","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1364\/BOE.4.000900","volume":"4","author":"JR Rajian","year":"2013","unstructured":"Rajian, J. R., Shao, X., Chamberland, D. L. & Wang, X. Characterization and treatment monitoring of inflammatory arthritis by photoacoustic imaging: a study on adjuvant-induced arthritis rat model. Biomedical optics express \n                           4, 900\u2013908, https:\/\/doi.org\/10.1364\/BOE.4.000900 (2013).","journal-title":"Biomedical optics express"},{"key":"15147_CR32","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1002\/art.38642","volume":"66","author":"N Beziere","year":"2014","unstructured":"Beziere, N. et al. Optoacoustic imaging and staging of inflammation in a murine model of arthritis. Arthritis & rheumatology \n                           66, 2071\u20132078, https:\/\/doi.org\/10.1002\/art.38642 (2014).","journal-title":"Arthritis & rheumatology"},{"key":"15147_CR33","doi-asserted-by":"publisher","first-page":"26365","DOI":"10.1364\/OE.22.026365","volume":"22","author":"K Daoudi","year":"2014","unstructured":"Daoudi, K. et al. Handheld probe integrating laser diode and ultrasound transducer array for ultrasound\/photoacoustic dual modality imaging. Opt Express \n                           22, 26365\u201326374, https:\/\/doi.org\/10.1364\/OE.22.026365 (2014).","journal-title":"Opt Express"},{"key":"15147_CR34","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1109\/TUFFC.2015.007058","volume":"62","author":"E Mercep","year":"2015","unstructured":"Mercep, E., Jeng, G., Morscher, S., Li, P. C. & Razansky, D. Hybrid Optoacoustic Tomography and Pulse-Echo Ultrasonography Using Concave Arrays. Ieee T Ultrason Ferr \n                           62, 1651\u20131661, https:\/\/doi.org\/10.1109\/Tuffc.2015.007058 (2015).","journal-title":"Ieee T Ultrason Ferr"},{"key":"15147_CR35","doi-asserted-by":"crossref","unstructured":"Dean-Ben, X. L., Bay, E. & Razansky, D. Functional optoacoustic imaging of moving objects using microsecond-delay acquisition of multispectral three-dimensional tomographic data. Sci Rep-Uk \n                           4 (2014).","DOI":"10.1038\/srep05878"},{"key":"15147_CR36","doi-asserted-by":"publisher","first-page":"024015","DOI":"10.1117\/1.2192804","volume":"11","author":"X Wang","year":"2006","unstructured":"Wang, X., Xie, X., Ku, G., Wang, L. V. & Stoica, G. Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography. J Biomed Opt \n                           11, 024015, https:\/\/doi.org\/10.1117\/1.2192804 (2006).","journal-title":"J Biomed Opt"},{"key":"15147_CR37","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1364\/OL.36.001029","volume":"36","author":"Y Wang","year":"2011","unstructured":"Wang, Y. et al. In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure. Optics letters \n                           36, 1029\u20131031, https:\/\/doi.org\/10.1364\/OL.36.001029 (2011).","journal-title":"Optics letters"},{"key":"15147_CR38","doi-asserted-by":"publisher","first-page":"N1","DOI":"10.1088\/0031-9155\/58\/1\/N1","volume":"58","author":"LG Montilla","year":"2013","unstructured":"Montilla, L. G., Olafsson, R., Bauer, D. R. & Witte, R. S. Real-time photoacoustic and ultrasound imaging: a simple solution for clinical ultrasound systems with linear arrays. Physics in Medicine and Biology \n                           58, N1 (2013).","journal-title":"Physics in Medicine and Biology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15147-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15147-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15147-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T12:58:21Z","timestamp":1671800301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15147-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,3]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["15147"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-15147-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,3]]},"assertion":[{"value":"4 July 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15026"}}