{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:14:23Z","timestamp":1790280863752,"version":"4.1.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute for Biomedical Imaging and Bioengineering at the National Institutes of Health","award":["R01 EB013723"],"award-info":[{"award-number":["R01 EB013723"]}]},{"name":"McGinnis Medical Innovation Fellowship"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Studying the impact of antibiotic treatment on otitis media (OM), the leading cause of primary care office visits during childhood, is critical to develop appropriate treatment strategies. Tracking dynamic middle ear conditions during antibiotic treatment is not readily applicable in patients, due to the limited diagnostic techniques available to detect the smaller amount and variation of middle ear effusion (MEE) and middle ear bacterial biofilm, responsible for chronic and recurrent OM. To overcome these challenges, a handheld optical coherence tomography (OCT) system has been developed to monitor in vivo response of biofilms and MEEs in the OM-induced chinchilla model, the standard model for human OM. As a result, the formation of MEE as well as biofilm adherent to the tympanic membrane (TM) was longitudinally assessed as OM developed. Various types of MEEs and biofilms in the chinchilla model were identified, which showed comparable features as those in humans. Furthermore, the effect of antibiotics on the biofilm as well as the amount and type of MEEs was investigated with low-dose and high-dose treatment (ceftriaxone). The capability of OCT to non-invasively track and examine middle ear conditions is highly beneficial for therapeutic OM studies and will lead to improved management of OM in patients.<\/jats:p>","DOI":"10.1038\/s41598-021-84543-9","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T11:04:29Z","timestamp":1614855869000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Longitudinal optical coherence tomography to visualize the in vivo response of middle ear biofilms to antibiotic therapy"],"prefix":"10.1038","volume":"11","author":[{"given":"Jungeun","family":"Won","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhou","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawjai","family":"Khampang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Darold R.","family":"Spillman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuels","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan G.","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Novak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Kerschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Boppart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"84543_CR1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1093\/infdis\/160.1.83","volume":"160","author":"DW Teele","year":"1989","unstructured":"Teele, D. W., Klein, J. O. & Rosner, B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: A prospective, cohort study. J. Infect. Dis. 160, 83\u201394 (1989).","journal-title":"J. Infect. Dis."},{"key":"84543_CR2","doi-asserted-by":"publisher","first-page":"3096","DOI":"10.1001\/jama.287.23.3096","volume":"287","author":"LF McCaig","year":"2002","unstructured":"McCaig, L. F., Besser, R. E. & Hughes, J. M. Trends in antimicrobial prescribing rates for children and adolescents. J. Am. Med. Assoc. 287, 3096\u20133102 (2002).","journal-title":"J. Am. Med. Assoc."},{"key":"84543_CR3","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/S0140-6736(05)17907-0","volume":"365","author":"H Goossens","year":"2005","unstructured":"Goossens, H., Ferech, M., Vander Stichele, R. & Elseviers, M. Outpatient antibiotic use in Europe and association with resistance: A cross-national database study. Lancet 365, 579\u2013587 (2005).","journal-title":"Lancet"},{"key":"84543_CR4","doi-asserted-by":"publisher","first-page":"e964","DOI":"10.1542\/peds.2012-3488","volume":"131","author":"AS Lieberthal","year":"2013","unstructured":"Lieberthal, A. S. et al. The diagnosis and management of acute otitis media. Pediatrics 131, e964\u2013e999 (2013).","journal-title":"Pediatrics"},{"key":"84543_CR5","first-page":"685","volume":"63","author":"T Sakulchit","year":"2017","unstructured":"Sakulchit, T. & Goldman, R. D. Antibiotic therapy for children with acute otitis media. Can. Fam. Physician 63, 685\u2013687 (2017).","journal-title":"Can. Fam. Physician"},{"key":"84543_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fped.2013.00052","volume":"1","author":"JM Coticchia","year":"2013","unstructured":"Coticchia, J. M., Chen, M., Sachdeva, L. & Mutchnick, S. New paradigms in the pathogenesis of otitis media in children. Front. Pediatr. 1, 1\u20137 (2013).","journal-title":"Front. Pediatr."},{"key":"84543_CR7","doi-asserted-by":"publisher","first-page":"671","DOI":"10.3390\/jcm8050671","volume":"8","author":"S Torretta","year":"2019","unstructured":"Torretta, S., Drago, L., Marchisio, P., Ibba, T. & Pignataro, L. Role of biofilms in children with chronic adenoiditis and middle ear disease. J. Clin. Med. 8, 671 (2019).","journal-title":"J. Clin. Med."},{"key":"84543_CR8","volume-title":"Evidence-Based Otitis Media","author":"M Casselbrant","year":"1999","unstructured":"Casselbrant, M. & Mandel, E. M. In Evidence-Based Otitis Media 2nd edn (eds Rosenfeld, R. M. & Bluestone, C. D.) (PMPH-USA, Shelton, 1999).","edition":"2"},{"key":"84543_CR9","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1001\/jama.296.2.202","volume":"296","author":"L Hall-Stoodley","year":"2006","unstructured":"Hall-Stoodley, L. et al. Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. J. Am. Med. Assoc. 296, 202\u2013211 (2006).","journal-title":"J. Am. Med. Assoc."},{"key":"84543_CR10","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1177\/0194599818766320","volume":"159","author":"GL Monroy","year":"2018","unstructured":"Monroy, G. L. et al. Direct analysis of pathogenic structures affixed to the tympanic membrane during chronic otitis media. Otolaryngol. Head Neck Surg. 159, 117\u2013126 (2018).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"84543_CR11","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1097\/00005537-200112000-00001","volume":"111","author":"JC Post","year":"2001","unstructured":"Post, J. C. Direct evidence of bacterial biofilms in otitis media. Laryngoscope 111, 2083\u20132094 (2001).","journal-title":"Laryngoscope"},{"key":"84543_CR12","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1093\/jpids\/pix008","volume":"7","author":"A Ruohola","year":"2018","unstructured":"Ruohola, A., Laine, M. K. & T\u00e4htinen, P. A. Effect of antimicrobial treatment on the resolution of middle-ear effusion after acute otitis media. J. Pediatr. Infect. Dis. Soc. 7, 64\u201370 (2018).","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"84543_CR13","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1503\/cmaj.1040771","volume":"172","author":"N Le Saux","year":"2005","unstructured":"Le Saux, N. et al. A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age. Can. Med. Assoc. J. 172, 335\u2013341 (2005).","journal-title":"Can. Med. Assoc. J."},{"key":"84543_CR14","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1126\/science.1957169","volume":"254","author":"D Huang","year":"1991","unstructured":"Huang, D. et al. Optical coherence tomography. Science 254, 1178\u20131181 (1991).","journal-title":"Science"},{"key":"84543_CR15","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.1442-9071.2008.01823.x","volume":"37","author":"JLB Ramos","year":"2009","unstructured":"Ramos, J. L. B., Li, Y. & Huang, D. Clinical and research applications of anterior segment optical coherence tomography\u2014A review. Clin. Exp. Ophthalmol. 37, 81\u201389 (2009).","journal-title":"Clin. Exp. Ophthalmol."},{"key":"84543_CR16","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1097\/CRD.0000000000000128","volume":"25","author":"SD Matthews","year":"2017","unstructured":"Matthews, S. D. & Frishman, W. H. A review of the clinical utility of intravascular ultrasound and optical coherence tomography in the assessment and treatment of coronary artery disease. Cardiol. Rev. 25, 68\u201376 (2017).","journal-title":"Cardiol. Rev."},{"key":"84543_CR17","first-page":"1","volume":"22","author":"J Wang","year":"2017","unstructured":"Wang, J., Xu, Y. & Boppart, S. A. Review of optical coherence tomography in oncology. J. Biomed. Opt. 22, 1 (2017).","journal-title":"J. Biomed. Opt."},{"key":"84543_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1034\/j.1600-0846.2001.007001001.x","volume":"7","author":"J Welzel","year":"2001","unstructured":"Welzel, J. Optical coherence tomography in dermatology: A review. Ski. Res. Tecnol. 7, 1\u20139 (2001).","journal-title":"Ski. Res. Tecnol."},{"key":"84543_CR19","doi-asserted-by":"crossref","unstructured":"Ramier, A., Rosowski, J. J. & Yun, S. Optical coherence tomography for imaging the middle and inner ears\u202f: A technical review. AIP Conf. Proc. 1965 (2018).","DOI":"10.1063\/1.5038448"},{"key":"84543_CR20","doi-asserted-by":"publisher","first-page":"056008","DOI":"10.1117\/1.JBO.20.5.056008","volume":"20","author":"D MacDougall","year":"2015","unstructured":"MacDougall, D., Rainsbury, J., Brown, J., Bance, M. & Adamson, R. Optical coherence tomography system requirements for clinical diagnostic middle ear imaging. J. Biomed. Opt. 20, 056008 (2015).","journal-title":"J. Biomed. Opt."},{"key":"84543_CR21","doi-asserted-by":"publisher","first-page":"106","DOI":"10.21053\/ceo.2019.00766","volume":"13","author":"S-J Oh","year":"2020","unstructured":"Oh, S.-J. et al. Extratympanic observation of middle and inner ear structures in rodents using optical coherence tomography. Clin. Exp. Otorhinolaryngol. 13, 106\u2013112 (2020).","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"84543_CR22","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1177\/0194599818775711","volume":"159","author":"HEI Tan","year":"2018","unstructured":"Tan, H. E. I. et al. Optical coherence tomography of the tympanic membrane and middle ear: A review. Otolaryngol. Head Neck Surg. 159, 424\u2013438 (2018).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"84543_CR23","doi-asserted-by":"publisher","first-page":"9529","DOI":"10.1073\/pnas.1201592109","volume":"109","author":"CT Nguyen","year":"2012","unstructured":"Nguyen, C. T. et al. Noninvasive in vivo optical detection of biofilm in the human middle ear. Proc. Natl. Acad. Sci. 109, 9529\u20139534 (2012).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"84543_CR24","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1097\/AUD.0000000000000796","volume":"41","author":"J Won","year":"2020","unstructured":"Won, J. et al. Assessing the effect of middle ear effusions on wideband acoustic immittance using optical coherence tomography. Ear Hear. 41, 811\u2013824 (2020).","journal-title":"Ear Hear."},{"key":"84543_CR25","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1177\/0194599819900762","volume":"162","author":"D Preciado","year":"2020","unstructured":"Preciado, D. et al. Otitis media middle ear effusion identification and characterization using an optical coherence tomography otoscope. Otolaryngol. Head Neck Surg. 162, 367\u2013374 (2020).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"84543_CR26","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.ijporl.2010.05.009","volume":"74","author":"JE Kerschner","year":"2010","unstructured":"Kerschner, J. E., Khampang, P. & Samuels, T. Extending the chinchilla middle ear epithelial model for mucin gene investigation. Int. J. Pediatr. Otorhinolaryngol. 74, 980\u2013985 (2010).","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"84543_CR27","doi-asserted-by":"publisher","first-page":"baw073","DOI":"10.1093\/database\/baw073","volume":"2016","author":"M Shimoyama","year":"2016","unstructured":"Shimoyama, M. et al. The chinchilla research resource database: Resource for an otolaryngology disease model. Database 2016, baw073 (2016).","journal-title":"Database"},{"key":"84543_CR28","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1586\/erv.09.63","volume":"8","author":"LO Bakaletz","year":"2009","unstructured":"Bakaletz, L. O. Chinchilla as a robust, reproducible and polymicrobial model of otitis media and its prevention. Expert Rev. Vaccines 8, 1063\u20131082 (2009).","journal-title":"Expert Rev. Vaccines"},{"key":"84543_CR29","doi-asserted-by":"publisher","first-page":"E276","DOI":"10.1002\/lary.25141","volume":"125","author":"GL Monroy","year":"2015","unstructured":"Monroy, G. L. et al. Noninvasive depth-resolved optical measurements of the tympanic membrane and middle ear for differentiating otitis media. Laryngoscope 125, E276\u2013E282 (2015).","journal-title":"Laryngoscope"},{"key":"84543_CR30","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1086\/597042","volume":"199","author":"SD Reid","year":"2009","unstructured":"Reid, S. D. et al. Streptococcus pneumoniae forms surface-attached communities in the middle ear of experimentally infected chinchillas. J. Infect. Dis. 199, 786\u2013794 (2009).","journal-title":"J. Infect. Dis."},{"key":"84543_CR31","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/INF.0b013e318154b273","volume":"26","author":"LO Bakaletz","year":"2007","unstructured":"Bakaletz, L. O. Bacterial biofilms in otitis media: Evidence and relevance. Pediatr. Infect. Dis. J. 26, 17\u201319 (2007).","journal-title":"Pediatr. Infect. Dis. J."},{"key":"84543_CR32","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1177\/0194599818809337","volume":"160","author":"T Marom","year":"2019","unstructured":"Marom, T., Kraus, O., Habashi, N. & Tamir, S. O. Emerging technologies for the diagnosis of otitis media. Otolaryngol. Head Neck Surg. 160, 447\u2013456 (2019).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"84543_CR33","doi-asserted-by":"publisher","first-page":"328","DOI":"10.3346\/jkms.2015.30.3.328","volume":"30","author":"NH Cho","year":"2015","unstructured":"Cho, N. H., Lee, S. H., Jung, W., Jang, J. H. & Kim, J. Optical coherence tomography for the diagnosis and evaluation of human otitis media. J. Korean Med. Sci. 30, 328\u2013335 (2015).","journal-title":"J. Korean Med. Sci."},{"key":"84543_CR34","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1364\/BOE.9.000397","volume":"9","author":"J Won","year":"2018","unstructured":"Won, J. et al. Pneumatic low-coherence interferometry otoscope to quantify tympanic membrane mobility and middle ear pressure. Biomed. Opt. Express 9, 83\u201394 (2018).","journal-title":"Biomed. Opt. Express"},{"key":"84543_CR35","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1002\/jbio.201500313","volume":"10","author":"GL Monroy","year":"2016","unstructured":"Monroy, G. L. et al. Non-invasive optical assessment of viscosity of middle ear effusions in otitis media. J. Biophotonics 10, 394\u2013403 (2016).","journal-title":"J. Biophotonics"},{"key":"84543_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41746-019-0094-0","volume":"2","author":"GL Monroy","year":"2019","unstructured":"Monroy, G. L. et al. Automated classification platform for the identification of otitis media using optical coherence tomography. npj Digit. Med. 2, 1\u201311 (2019).","journal-title":"npj Digit. Med."},{"key":"84543_CR37","doi-asserted-by":"publisher","first-page":"081006","DOI":"10.1115\/1.4030410","volume":"137","author":"Z Yokell","year":"2015","unstructured":"Yokell, Z., Wang, X. & Gan, R. Z. Dynamic properties of tympanic membrane in a chinchilla otitis media model measured with acoustic loading. J. Biomech. Eng. 137, 081006 (2015).","journal-title":"J. Biomech. Eng."},{"key":"84543_CR38","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.ijporl.2019.07.002","volume":"125","author":"W Hong","year":"2019","unstructured":"Hong, W. et al. Antibiotic modulation of mucins in otitis media; should this change our approach to watchful waiting?. Int. J. Pediatr. Otorhinolaryngol. 125, 134\u2013140 (2019).","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"84543_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1117\/1.JBO.22.12.121614","volume":"22","author":"GL Monroy","year":"2017","unstructured":"Monroy, G. L., Won, J., Spillman, D. R., Dsouza, R. & Boppart, S. A. Clinical translation of handheld optical coherence tomography: Practical considerations and recent advancements. J. Biomed. Opt. 22, 1\u201330 (2017).","journal-title":"J. Biomed. Opt."},{"key":"84543_CR40","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1097\/OPX.0000000000000892","volume":"93","author":"P Tankam","year":"2016","unstructured":"Tankam, P., Won, J., Canavesi, C., Cox, I. & Rolland, J. P. Optical assessment of soft contact lens edge-thickness. Optom. Vis. Sci. 93, 987\u2013996 (2016).","journal-title":"Optom. Vis. Sci."},{"key":"84543_CR41","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1126\/science.1061217","volume":"293","author":"H Tettelin","year":"2001","unstructured":"Tettelin, H. et al. Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293, 498\u2013506 (2001).","journal-title":"Science"},{"key":"84543_CR42","doi-asserted-by":"publisher","first-page":"4627","DOI":"10.1128\/JB.187.13.4627-4636.2005","volume":"187","author":"A Harrison","year":"2005","unstructured":"Harrison, A. et al. Genomic sequence of an otitis media isolate of nontypeable Haemophilusinfluenzae: Comparative study with H. influenzae serotype D, strain KW20. J. Bacteriol. 187, 4627\u20134636 (2005).","journal-title":"J. Bacteriol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84543-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84543-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84543-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T17:07:15Z","timestamp":1675012035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84543-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,4]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["84543"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-84543-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,4]]},"assertion":[{"value":"8 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.A.B. is a co-founder and Chief Medical Officer of PhotoniCare, Inc, which is commercializing OCT for imaging the ear. M.A.N. has equity interest in and serves on the clinical advisory board of PhotoniCare, Inc. The remaining authors do not have any conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5176"}}