{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:56:32Z","timestamp":1790542592590,"version":"4.1.0"},"reference-count":98,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"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>Identifying distinct normal extracellular matrix (ECM) features from pathology is of the upmost clinical importance for laryngeal diagnostics and therapy. Despite remarkable histological contributions, our understanding of the vocal fold (VF) physiology remains murky. The emerging field of non-invasive 3D optical imaging may be well-suited to unravel the complexity of the VF microanatomy. This study focused on characterizing the entire VF ECM in length and depth with optical imaging. A quantitative morphometric evaluation of the human vocal fold lamina propria using two-photon excitation fluorescence (TPEF), second harmonic generation (SHG), and optical coherence tomography (OCT) was investigated. Fibrillar morphological features, such as fiber diameter, orientation, anisotropy, waviness and second-order statistics features were evaluated and compared according to their spatial distribution. The evidence acquired in this study suggests that the VF ECM is not a strict discrete three-layer structure as traditionally described but instead a continuous assembly of different fibrillar arrangement anchored by predominant collagen transitions zones. We demonstrated that the ECM composition is distinct and markedly thinned in the anterior one-third of itself, which may play a role in the development of some laryngeal diseases. We further examined and extracted the relationship between OCT and multiphoton imaging, promoting correspondences that could lead to accurate 3D mapping of the VF architecture in real-time during phonosurgeries. As miniaturization of optical probes is consistently improving, a clinical translation of OCT imaging and multiphoton imaging, with valuable qualitative and quantitative features, may have significant implications for treating voice disorders.<\/jats:p>","DOI":"10.1038\/s41598-021-82157-9","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T11:04:39Z","timestamp":1611831879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Quantitative evaluation of the human vocal fold extracellular matrix using multiphoton microscopy and optical coherence tomography"],"prefix":"10.1038","volume":"11","author":[{"given":"Fouzi","family":"Benboujja","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Hartnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"82157_CR1","first-page":"239","volume":"1","author":"M Hirano","year":"1975","unstructured":"Hirano, M. Phonosurgery; basic & clinical investigations. Otologia 1, 239\u2013442 (1975).","journal-title":"Otologia"},{"key":"82157_CR2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1159\/000263771","volume":"26","author":"M Hirano","year":"1974","unstructured":"Hirano, M. Morphological structure of the vocal cord as a vibrator and its variations. Folia Phoniatr. Logop. 26, 89\u201394 (1974).","journal-title":"Folia Phoniatr. Logop."},{"key":"82157_CR3","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jvoice.2007.12.002","volume":"23","author":"S Hirano","year":"2009","unstructured":"Hirano, S. et al. Histologic characterization of human scarred vocal folds. J. Voice 23, 399\u2013407 (2009).","journal-title":"J. Voice"},{"key":"82157_CR4","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/0014-5793(90)81291-U","volume":"268","author":"J Labat-Robert","year":"1990","unstructured":"Labat-Robert, J., Bihari-Varga, M. & Robert, L. Extracellular matrix. FEBS Lett. 268, 386\u2013393 (1990).","journal-title":"FEBS Lett."},{"key":"82157_CR5","volume-title":"Clinical Voice Pathology: Theory and Management","author":"JC Stemple","year":"2014","unstructured":"Stemple, J. C., Roy, N. & Klaben, B. K. Clinical Voice Pathology: Theory and Management 5th edn. (Plural Publishing Incorporated, San Deigo, 2014).","edition":"5"},{"key":"82157_CR6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1177\/000348949710600109","volume":"106","author":"K Sato","year":"1997","unstructured":"Sato, K. & Hirano, M. Age-related changes of elastic fibers in the superficial layer of the lamina propria of vocal folds. Ann. Otol. Rhinol. Laryngol. 106, 44\u201348 (1997).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"82157_CR7","volume-title":"Growth, Development, and Aging of Human Vocal Folds","author":"KS Hirano","year":"1983","unstructured":"Hirano, K. S. Growth, Development, and Aging of Human Vocal Folds (College Hill Press, Sussex, 1983)."},{"issue":"1","key":"82157_CR8","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1177\/000348949710600109","volume":"106","author":"K Sato","year":"1997","unstructured":"Sato, K. & Hirano, M. Age-related changes of elastic fibers in the superficial layer of the lamina propria of vocal folds. Ann. Otol. Rhinol. Laryngol. 106(1), 44\u201348 (1997).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"82157_CR9","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00276-009-0577-9","volume":"32","author":"J-M Prades","year":"2010","unstructured":"Prades, J.-M. et al. Lamina propria of the human vocal fold: Histomorphometric study of collagen fibers. Surg. Radiol. Anat. 32, 377\u2013382 (2010).","journal-title":"Surg. Radiol. Anat."},{"key":"82157_CR10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1177\/000348940111000505","volume":"110","author":"K Sato","year":"2001","unstructured":"Sato, K., Hirano, M. & Nakashima, T. Fine structure of the human newborn and infant vocal fold mucosae. Ann. Otol. Rhinol. Laryngol. 110, 417\u2013424 (2001).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"82157_CR11","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0892-1997(05)80318-2","volume":"8","author":"SD Gray","year":"1994","unstructured":"Gray, S. D., Pignatari, S. S. & Harding, P. Morphologic ultrastructure of anchoring fibers in normal vocal fold basement membrane zone. J. Voice 8, 48\u201352 (1994).","journal-title":"J. Voice"},{"key":"82157_CR12","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1016\/j.ultrasmedbio.2009.06.002","volume":"35","author":"C-G Tsai","year":"2009","unstructured":"Tsai, C.-G., Chen, J.-H., Shau, Y.-W. & Hsiao, T.-Y. Dynamic B-mode ultrasound imaging of vocal fold vibration during phonation. Ultrasound Med. Biol. 35, 1812\u20131818 (2009).","journal-title":"Ultrasound Med. Biol."},{"key":"82157_CR13","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2214\/ajr.166.2.8553933","volume":"166","author":"AS Zeiberg","year":"1996","unstructured":"Zeiberg, A. S. et al. Helical (spiral) CT of the upper airway with three-dimensional imaging: technique and clinical assessment. Am. J. Roentgenol. 166, 293\u2013299 (1996).","journal-title":"Am. J. Roentgenol."},{"key":"82157_CR14","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.jvoice.2011.03.012","volume":"26","author":"T Chen","year":"2012","unstructured":"Chen, T. et al. A new method of reconstructing the human laryngeal architecture using micro-MRI. J. Voice 26, 555\u2013562 (2012).","journal-title":"J. Voice"},{"key":"82157_CR15","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1002\/lary.20643","volume":"119","author":"VLM Herrera","year":"2009","unstructured":"Herrera, V. L. M. et al. 11.7 Tesla magnetic resonance microimaging of laryngeal tissue architecture. Laryngoscope 119, 2187\u20132194 (2009).","journal-title":"Laryngoscope"},{"key":"82157_CR16","doi-asserted-by":"crossref","first-page":"14003","DOI":"10.1038\/s41598-018-31849-w","volume":"8","author":"L Bailly","year":"2018","unstructured":"Bailly, L. et al. 3D multiscale imaging of human vocal folds using synchrotron X-ray microtomography in phase retrieval mode. Sci. Rep. 8, 14003 (2018).","journal-title":"Sci. Rep."},{"key":"82157_CR17","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1364\/BOE.10.001151","volume":"10","author":"A Kazarine","year":"2019","unstructured":"Kazarine, A. et al. Multimodal virtual histology of rabbit vocal folds by nonlinear microscopy and nano computed tomography. Biomed. Opt. Express 10, 1151 (2019).","journal-title":"Biomed. Opt. Express"},{"key":"82157_CR18","doi-asserted-by":"crossref","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":"82157_CR19","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nmeth818","volume":"2","author":"F Helmchen","year":"2005","unstructured":"Helmchen, F. & Denk, W. Deep tissue two-photon microscopy. Nat. Methods 2, 932\u2013940 (2005).","journal-title":"Nat. Methods"},{"key":"82157_CR20","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/nbt892","volume":"21","author":"JG Fujimoto","year":"2003","unstructured":"Fujimoto, J. G. Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat. Biotechnol. 21, 1361\u20131367 (2003).","journal-title":"Nat. Biotechnol."},{"key":"82157_CR21","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1364\/OPEX.12.002112","volume":"12","author":"TH Ko","year":"2004","unstructured":"Ko, T. H. et al. Ultrahigh resolution optical coherence tomography imaging with a broadband superluminescent diode light source. Opt. Express 12, 2112 (2004).","journal-title":"Opt. Express"},{"key":"82157_CR22","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1364\/OPEX.12.002404","volume":"12","author":"M Wojtkowski","year":"2004","unstructured":"Wojtkowski, M. et al. Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation. Opt. Express 12, 2404 (2004).","journal-title":"Opt. Express"},{"key":"82157_CR23","doi-asserted-by":"crossref","first-page":"3598","DOI":"10.1364\/OE.11.003598","volume":"11","author":"S Yun","year":"2003","unstructured":"Yun, S., Tearney, G., Bouma, B., Park, B. & de Boer, J. High-speed spectral-domain optical coherence tomography at 13 \u03bcm wavelength. Opt. Express 11, 3598\u20133604 (2003).","journal-title":"Opt. Express"},{"key":"82157_CR24","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1097\/MLG.0b013e318145b306","volume":"117","author":"JM Ridgway","year":"2007","unstructured":"Ridgway, J. M. et al. Imaging of the pediatric airway using optical coherence tomography. Laryngoscope 117, 2206\u20132212 (2007).","journal-title":"Laryngoscope"},{"key":"82157_CR25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ijporl.2014.11.019","volume":"79","author":"V Volgger","year":"2015","unstructured":"Volgger, V. et al. Long-range Fourier domain optical coherence tomography of the pediatric subglottis. Int. J. Pediatr. Otorhinolaryngol. 79, 119\u2013126 (2015).","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"82157_CR26","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1177\/0003489416655353","volume":"125","author":"GK Sharma","year":"2016","unstructured":"Sharma, G. K. et al. Quantitative evaluation of adult subglottic stenosis using intraoperative long-range optical coherence tomography. Ann. Otol. Rhinol. Laryngol. 125, 815\u2013822 (2016).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"82157_CR27","first-page":"327","volume":"117","author":"JM Ridgway","year":"2008","unstructured":"Ridgway, J. M. et al. Optical coherence tomography of the newborn airway. Ann. Otol. Rhinol. Laryngol. 117, 327\u2013334 (2008).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"82157_CR28","doi-asserted-by":"crossref","first-page":"11880","DOI":"10.1364\/OE.19.011880","volume":"19","author":"G Liu","year":"2011","unstructured":"Liu, G. et al. Imaging vibrating vocal folds with a high speed 1050 nm swept source OCT and ODT. Opt. Express 19, 11880 (2011).","journal-title":"Opt. Express"},{"key":"82157_CR29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep22792","volume":"6","author":"CA Coughlan","year":"2016","unstructured":"Coughlan, C. A. et al. In vivo cross-sectional imaging of the phonating larynx using long-range Doppler optical coherence tomography. Sci. Rep. 6, 1\u20139 (2016).","journal-title":"Sci. Rep."},{"key":"82157_CR30","volume-title":"Normal & Abnormal Vocal Folds Kinematics: High-Speed Digital Phonoscopy (HSDP), Optical Coherence Tomography (OCT) & Narrow Band Imaging (NBI)","author":"C Boudoux","year":"2015","unstructured":"Boudoux, C. et al. Emerging microscopy techniques for pediatric vocal fold evaluation. In Normal & Abnormal Vocal Folds Kinematics: High-Speed Digital Phonoscopy (HSDP), Optical Coherence Tomography (OCT) & Narrow Band Imaging (NBI) (eds Izdebski, K. et al.) (Springer, New York, 2015)."},{"key":"82157_CR31","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1002\/lary.20654","volume":"119","author":"JA Burns","year":"2009","unstructured":"Burns, J. A. et al. Real-time tracking of vocal fold injections with optical coherence tomography. Laryngoscope 119, 2182\u20132186 (2009).","journal-title":"Laryngoscope"},{"key":"82157_CR32","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jvoice.2007.10.003","volume":"23","author":"C Boudoux","year":"2009","unstructured":"Boudoux, C. et al. Preliminary evaluation of noninvasive microscopic imaging techniques for the study of vocal fold development. J. Voice 23, 269\u2013276 (2009).","journal-title":"J. Voice"},{"key":"82157_CR33","doi-asserted-by":"publisher","DOI":"10.1117\/1.JBO.21.1.016007","author":"F Benboujja","year":"2016","unstructured":"Benboujja, F. et al. Intraoperative imaging of pediatric vocal fold lesions using optical coherence tomography. J. Biomed. Opt. https:\/\/doi.org\/10.1117\/1.JBO.21.1.016007 (2016).","journal-title":"J. Biomed. Opt."},{"key":"82157_CR34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ijporl.2018.08.036","volume":"114","author":"F Benboujja","year":"2018","unstructured":"Benboujja, F. & Hartnick, C. Clinical and surgical implications of intraoperative optical coherence tomography imaging for benign pediatric vocal fold lesions. Int. J. Pediatr. Otorhinolaryngol. 114, 111\u2013119 (2018).","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"82157_CR35","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1001\/jamaoto.2018.1375","volume":"144","author":"F Benboujja","year":"2018","unstructured":"Benboujja, F., Bowe, S., Boudoux, C. & Hartnick, C. Utility of optical coherence tomography for guiding laser therapy among patients with recurrent respiratory papillomatosis. JAMA Otolaryngol. Head Neck Surg. 144, 831\u2013837 (2018).","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"82157_CR36","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1097\/01.MLG.0000181465.17744.BE","volume":"115","author":"BJF Wong","year":"2005","unstructured":"Wong, B. J. F. et al. In vivo optical coherence tomography of the human larynx: normative and benign pathology in 82 patients. Laryngoscope 115, 1904\u20131911 (2005).","journal-title":"Laryngoscope"},{"key":"82157_CR37","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/lary.26241","volume":"127","author":"O Ajose-Popoola","year":"2017","unstructured":"Ajose-Popoola, O. et al. Diagnosis of subglottic stenosis in a rabbit model using long-range optical coherence tomography. Laryngoscope 127, 64\u201369 (2017).","journal-title":"Laryngoscope"},{"key":"82157_CR38","doi-asserted-by":"crossref","first-page":"E218","DOI":"10.1002\/lary.25765","volume":"126","author":"J Gracia","year":"2016","unstructured":"Gracia, J. et al. Using attenuation coefficients from optical coherence tomography as markers of vocal fold maturation. Laryngoscope 126, E218\u2013E223 (2016).","journal-title":"Laryngoscope"},{"key":"82157_CR39","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1177\/000348941212101109","volume":"121","author":"S Maturo","year":"2012","unstructured":"Maturo, S., Benboujja, F., Boudoux, C. & Hartnick, C. Quantitative distinction of unique vocal fold subepithelial architectures using optical coherence tomography. Ann. Otol. Rhinol. Laryngol. 121, 754\u2013760 (2012).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"82157_CR40","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1038\/nbt899","volume":"21","author":"WR Zipfel","year":"2003","unstructured":"Zipfel, W. R., Williams, R. M. & Webb, W. W. Nonlinear magic: Multiphoton microscopy in the biosciences. Nat. Biotechnol. 21, 1369\u20131377 (2003).","journal-title":"Nat. Biotechnol."},{"key":"82157_CR41","doi-asserted-by":"crossref","first-page":"7075","DOI":"10.1073\/pnas.0832308100","volume":"100","author":"WR Zipfel","year":"2003","unstructured":"Zipfel, W. R. et al. Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc. Natl. Acad. Sci. 100, 7075\u20137080 (2003).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"82157_CR42","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1016\/S0006-3495(02)75621-X","volume":"82","author":"S Huang","year":"2002","unstructured":"Huang, S., Heikal, A. A. & Webb, W. W. Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein. Biophys. J. 82, 2811\u20132825 (2002).","journal-title":"Biophys. J."},{"key":"82157_CR43","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nprot.2012.009","volume":"7","author":"X Chen","year":"2012","unstructured":"Chen, X., Nadiarynkh, O., Plotnikov, S. & Campagnola, P. J. Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure. Nat. Protoc. 7, 654\u2013669 (2012).","journal-title":"Nat. Protoc."},{"key":"82157_CR44","doi-asserted-by":"crossref","first-page":"038002","DOI":"10.1117\/1.JBO.17.3.038002","volume":"17","author":"CL Hoy","year":"2012","unstructured":"Hoy, C. L. et al. Towards endoscopic ultrafast laser microsurgery of vocal folds. J. Biomed. Opt. 17, 038002 (2012).","journal-title":"J. Biomed. Opt."},{"key":"82157_CR45","volume-title":"Biomedical Optics in Otorhinolaryngology, Head and Neck Surgery: Principles and Practice","author":"M Strupler","year":"2015","unstructured":"Strupler, M. et al. Nonlinear microscopy of the vocal folds. In Biomedical Optics in Otorhinolaryngology, Head and Neck Surgery: Principles and Practice (eds Wong, B.J.-F. & Ilgner, J.) (Springer, New York, 2015)."},{"key":"82157_CR46","doi-asserted-by":"crossref","first-page":"096013","DOI":"10.1117\/1.JBO.20.9.096013","volume":"20","author":"M Yildirim","year":"2015","unstructured":"Yildirim, M., Durr, N. & Ben-Yakar, A. Tripling the maximum imaging depth with third-harmonic generation microscopy. J. Biomed. Opt. 20, 096013 (2015).","journal-title":"J. Biomed. Opt."},{"key":"82157_CR47","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/lary.22460","volume":"122","author":"AK Miri","year":"2012","unstructured":"Miri, A. K., Tripathy, U., Mongeau, L. & Wiseman, P. W. Nonlinear laser scanning microscopy of human vocal folds. Laryngoscope 122, 356\u2013363 (2012).","journal-title":"Laryngoscope"},{"key":"82157_CR48","first-page":"1","volume":"12","author":"A Li","year":"2019","unstructured":"Li, A. et al. A biopsy-needle compatible varifocal multiphoton rigid probe for depth-resolved optical biopsy. J. Biophotonics 12, 1\u201311 (2019).","journal-title":"J. Biophotonics"},{"key":"82157_CR49","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: An open-source platform for biological-image analysis. Nat. Methods 9, 676\u2013682 (2012).","journal-title":"Nat. Methods"},{"key":"82157_CR50","doi-asserted-by":"crossref","first-page":"7857","DOI":"10.1364\/OE.18.007857","volume":"18","author":"HG Breunig","year":"2010","unstructured":"Breunig, H. G., Studier, H. & K\u00f6nig, K. Multiphoton excitation characteristics of cellular fluorophores of human skin in vivo. Opt. Express 18, 7857 (2010).","journal-title":"Opt. Express"},{"key":"82157_CR51","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/1471-2105-13-316","volume":"13","author":"A Bria","year":"2012","unstructured":"Bria, A. & Iannello, G. TeraStitcher: A tool for fast automatic 3D-stitching of teravoxel-sized microscopy images. BMC Bioinformatics 13, 316 (2012).","journal-title":"BMC Bioinformatics"},{"key":"82157_CR52","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1364\/BOE.9.003923","volume":"9","author":"R Hristu","year":"2018","unstructured":"Hristu, R. et al. Quantitative second harmonic generation microscopy for the structural characterization of capsular collagen in thyroid neoplasms. Biomed. Opt. Express 9, 3923 (2018).","journal-title":"Biomed. Opt. Express"},{"key":"82157_CR53","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/jbio.200910062","volume":"3","author":"R Cicchi","year":"2010","unstructured":"Cicchi, R. et al. Scoring of collagen organization in healthy and diseased human dermis by multiphoton microscopy. J. Biophotonics 3, 34\u201343 (2010).","journal-title":"J. Biophotonics"},{"key":"82157_CR54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1117\/1.JBO.24.9.096001","volume":"24","author":"KM Kozlowski","year":"2019","unstructured":"Kozlowski, K. M. et al. Dynamic programming and automated segmentation of optical coherence tomography images of the neonatal subglottis: Enabling efficient diagnostics to manage subglottic stenosis. J. Biomed. Opt. 24, 1 (2019).","journal-title":"J. Biomed. Opt."},{"key":"82157_CR55","doi-asserted-by":"crossref","first-page":"026007","DOI":"10.1117\/1.JBO.17.2.026007","volume":"17","author":"W Hu","year":"2012","unstructured":"Hu, W., Li, H., Wang, C., Gou, S. & Fu, L. Characterization of collagen fibers by means of texture analysis of second harmonic generation images using orientation-dependent gray level co-occurrence matrix method. J. Biomed. Opt. 17, 026007 (2012).","journal-title":"J. Biomed. Opt."},{"key":"82157_CR56","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1109\/TSMC.1973.4309314","volume":"3","author":"RM Haralick","year":"1973","unstructured":"Haralick, R. M., Shanmugam, K. & Dinstein, I. Textural Features for Image Classification. IEEE Trans. Syst. Man. Cybern. 3, 610\u2013621 (1973).","journal-title":"IEEE Trans. Syst. Man. Cybern."},{"key":"82157_CR57","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1038\/srep02190","volume":"3","author":"LB Mosta\u00e7o-Guidolin","year":"2013","unstructured":"Mosta\u00e7o-Guidolin, L. B. et al. Collagen morphology and texture analysis: from statistics to classification. Sci. Rep. 3, 2190 (2013).","journal-title":"Sci. Rep."},{"key":"82157_CR58","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1016\/j.bpj.2014.05.014","volume":"106","author":"MJ Chow","year":"2014","unstructured":"Chow, M. J., Turcotte, R., Lin, C. P. & Zhang, Y. Arterial extracellular matrix: A mechanobiological study of the contributions and interactions of elastin and collagen. Biophys. J. 106, 2684\u20132692 (2014).","journal-title":"Biophys. J."},{"key":"82157_CR59","doi-asserted-by":"crossref","first-page":"5524","DOI":"10.1016\/j.biomaterials.2006.06.014","volume":"27","author":"C Ayres","year":"2010","unstructured":"Ayres, C. et al. Scaffolds: Analysis of fiber alignment by the fast Fourier transform. Biomaterials 27, 5524\u20135534 (2010).","journal-title":"Biomaterials"},{"key":"82157_CR60","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1098\/rsif.2005.0073","volume":"3","author":"TC Gasser","year":"2006","unstructured":"Gasser, T. C., Ogden, R. W. & Holzapfel, G. A. Hyperelastic modelling of arterial layers with distributed collagen fibre orientations. J. R. Soc. Interface 3, 15\u201335 (2006).","journal-title":"J. R. Soc. Interface"},{"key":"82157_CR61","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s10237-005-0069-8","volume":"4","author":"AD Freed","year":"2005","unstructured":"Freed, A. D., Einstein, D. R. & Vesely, I. Invariant formulation for dispersed transverse isotropy in aortic heart valves: An efficient means for modeling fiber splay. Biomech. Model. Mechanobiol. 4, 100\u2013117 (2005).","journal-title":"Biomech. Model. Mechanobiol."},{"key":"82157_CR62","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s10237-011-0325-z","volume":"11","author":"R Rezakhaniha","year":"2012","unstructured":"Rezakhaniha, R. et al. Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy. Biomech. Model. Mechanobiol. 11, 461\u2013473 (2012).","journal-title":"Biomech. Model. Mechanobiol."},{"key":"82157_CR63","doi-asserted-by":"crossref","first-page":"9848","DOI":"10.1364\/AO.54.009848","volume":"54","author":"FJ \u00c1vila","year":"2015","unstructured":"\u00c1vila, F. J. & Bueno, J. M. Analysis and quantification of collagen organization with the structure tensor in second harmonic microscopy images of ocular tissues. Appl. Opt. 54, 9848\u20139854 (2015).","journal-title":"Appl. Opt."},{"key":"82157_CR64","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/jemt.20033","volume":"63","author":"O Schmitt","year":"2004","unstructured":"Schmitt, O. et al. Analysis of nerve fibers and their distribution in histologic sections of the human brain. Microsc. Res. Tech. 63, 220\u2013243 (2004).","journal-title":"Microsc. Res. Tech."},{"key":"82157_CR65","volume-title":"A Practical Guide to Splines","author":"C de Boor","year":"1980","unstructured":"de Boor, C. A Practical Guide to Splines (Springer, New York, 1980)."},{"key":"82157_CR66","doi-asserted-by":"crossref","DOI":"10.1007\/3-540-57418-2","volume-title":"Spatio-Temporal Image Processing. Lecture Notes in Computer Science","author":"B Jahne","year":"1993","unstructured":"Jahne, B. Spatio-Temporal Image Processing. Lecture Notes in Computer Science (Springer, Berlin Heidelberg, 1993)."},{"key":"82157_CR67","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-28549-8","author":"Z P\u00fcsp\u00f6ki","year":"2016","unstructured":"P\u00fcsp\u00f6ki, Z., Storath, M., Sage, D. & Unser, M. Transforms and operators for directional bioimage analysis: a Survey. Focus Bio-Image Inform. https:\/\/doi.org\/10.1007\/978-3-319-28549-8 (2016).","journal-title":"Focus Bio-Image Inform."},{"key":"82157_CR68","doi-asserted-by":"crossref","first-page":"011105","DOI":"10.1117\/1.3280271","volume":"15","author":"G van Soest","year":"2010","unstructured":"van Soest, G. et al. Atherosclerotic tissue characterization in vivo by optical coherence tomography attenuation imaging. J. Biomed. Opt. 15, 011105 (2010).","journal-title":"J. Biomed. Opt."},{"key":"82157_CR69","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10103-005-0336-z","volume":"20","author":"FJ Van Der Meer","year":"2005","unstructured":"Van Der Meer, F. J. et al. Quantitative optical coherence tomography of arterial wall components. Lasers Med. Sci. 20, 45\u201351 (2005).","journal-title":"Lasers Med. Sci."},{"key":"82157_CR70","doi-asserted-by":"crossref","first-page":"046029","DOI":"10.1117\/1.3479931","volume":"15","author":"RA McLaughlin","year":"2010","unstructured":"McLaughlin, R. A. et al. Parametric imaging of cancer with optical coherence tomography. J. Biomed. Opt. 15, 046029 (2010).","journal-title":"J. Biomed. Opt."},{"key":"82157_CR71","doi-asserted-by":"crossref","first-page":"6102","DOI":"10.1167\/iovs.12-9933","volume":"53","author":"KA Vermeer","year":"2012","unstructured":"Vermeer, K. A., van der Schoot, J., Lemij, H. G. & de Boer, J. F. RPE-normalized RNFL attenuation coefficient maps derived from volumetric OCT imaging for glaucoma assessment. Investig. Ophthalmol. Vis. Sci. 53, 6102\u20136108 (2012).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"82157_CR72","doi-asserted-by":"crossref","first-page":"066003","DOI":"10.1117\/1.3505019","volume":"15","author":"PH Tomlins","year":"2010","unstructured":"Tomlins, P. H. et al. Scattering attenuation microscopy of oral epithelial dysplasia. J. Biomed. Opt. 15, 066003 (2010).","journal-title":"J. Biomed. Opt."},{"key":"82157_CR73","doi-asserted-by":"crossref","first-page":"E218","DOI":"10.1002\/lary.25765","volume":"126","author":"JA Garcia","year":"2016","unstructured":"Garcia, J. A. et al. Using attenuation coefficients from optical coherence tomography as markers of vocal fold maturation. Laryngoscope 126, E218\u2013E233 (2016).","journal-title":"Laryngoscope"},{"key":"82157_CR74","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1177\/0194599816658005","volume":"155","author":"JA Garcia","year":"2016","unstructured":"Garcia, J. A. et al. Collagen content limits optical coherence tomography image depth in porcine vocal fold tissue. Otolaryngol. Head Neck Surg. 155, 829\u2013836 (2016).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"82157_CR75","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1364\/AO.42.003027","volume":"42","author":"AI Kholodnykh","year":"2003","unstructured":"Kholodnykh, A. I., Petrova, I. Y., Larin, K. V., Motamedi, M. & Esenaliev, R. O. Precision of measurement of tissue optical properties with optical coherence tomography. Appl. Opt. 42, 3027 (2003).","journal-title":"Appl. Opt."},{"key":"82157_CR76","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.jbiomech.2003.11.007","volume":"37","author":"HE Gunter","year":"2004","unstructured":"Gunter, H. E. Modeling mechanical stresses as a factor in the etiology of benign vocal fold lesions. J. Biomech. 37, 1119\u20131124 (2004).","journal-title":"J. Biomech."},{"key":"82157_CR77","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1364\/OL.20.002258","volume":"20","author":"GJ Tearney","year":"1995","unstructured":"Tearney, G. J. et al. Determination of the refractive index of highly scattering human tissue by optical coherence tomography. Opt. Lett. 20, 2258 (1995).","journal-title":"Opt. Lett."},{"key":"82157_CR78","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3109\/00016488909127535","volume":"107","author":"M Hirano","year":"1989","unstructured":"Hirano, M., Kurita, S. & Sakaguchi, S. Ageing of the vibratory tissue of human vocal folds. Acta Otolaryngol. 107, 428\u2013433 (1989).","journal-title":"Acta Otolaryngol."},{"key":"82157_CR79","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1679\/aohc.65.109","volume":"65","author":"T Ushiki","year":"2002","unstructured":"Ushiki, T. Collagen fibers, reticular fibers and elastic fibers. A comprehensive understanding from a morphological viewpoint. Arch. Histol. Cytol. 65, 109\u2013126 (2002).","journal-title":"Arch. Histol. Cytol."},{"key":"82157_CR80","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0892-1997(97)80024-0","volume":"11","author":"TH Hammond","year":"1997","unstructured":"Hammond, T. H., Zhou, R., Hammond, E. H., Pawlak, A. & Gray, S. D. The intermediate layer: a morphologic study of the elastin and hyaluronic acid constituents of normal human vocal folds. J. Voice 11, 59\u201366 (1997).","journal-title":"J. Voice"},{"key":"82157_CR81","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1177\/000348940010900115","volume":"109","author":"SD Gray","year":"2000","unstructured":"Gray, S. D., Titze, I. R., Alipour, F. & Hammond, T. H. Biomechanical and histologic observations of vocal fold fibrous proteins. Ann. Otol. Rhinol. Laryngol. 109, 77\u201385 (2000).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"82157_CR82","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1097\/MLG.0b013e3181770955","volume":"118","author":"FA Sakae","year":"2008","unstructured":"Sakae, F. A. et al. Disarrangement of collagen fibers in Reinke\u2019s edema. Laryngoscope 118, 1500\u20131503 (2008).","journal-title":"Laryngoscope"},{"key":"82157_CR83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1115\/1.3005331","volume":"131","author":"BA Roeder","year":"2009","unstructured":"Roeder, B. A., Kokini, K. & Voytik-Harbin, S. L. Fibril microstructure affects strain transmission within collagen extracellular matrices. J. Biomech. Eng. 131, 1\u201311 (2009).","journal-title":"J. Biomech. Eng."},{"key":"82157_CR84","doi-asserted-by":"crossref","first-page":"E313","DOI":"10.1002\/lary.25264","volume":"125","author":"JR Dowdall","year":"2015","unstructured":"Dowdall, J. R. et al. Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold. Laryngoscope 125, E313\u2013E319 (2015).","journal-title":"Laryngoscope"},{"key":"82157_CR85","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1044\/2014_JSLHR-S-13-0283","volume":"57","author":"EE Levendoski","year":"2014","unstructured":"Levendoski, E. E., Leydon, C. & Thibeault, S. L. Vocal fold epithelial barrier in health and injury: A research review. J. Speech Lang. Hear. Res. 57, 1679\u20131691 (2014).","journal-title":"J. Speech Lang. Hear. Res."},{"key":"82157_CR86","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3109\/00016489209137440","volume":"112","author":"T Haji","year":"1992","unstructured":"Haji, T., Mori, K., Omori, K. & Isshiki, N. Mechanical properties of the vocal fold. Stress-strain studies. Acta Otolaryngol. 112, 559\u2013565 (1992).","journal-title":"Acta Otolaryngol."},{"key":"82157_CR87","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1177\/000348940010900115","volume":"109","author":"SD Gray","year":"2000","unstructured":"Gray, S. D., Alipour, F., Titze, I. R. & Hammond, T. H. Biomechanical and histologic observations of vocal fold fibrous proteins. Ann. Otol. Rhinol. Laryngol. 109, 77\u201385 (2000).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"82157_CR88","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1097\/00005537-200312000-00027","volume":"113","author":"E Christiano","year":"2003","unstructured":"Christiano, E., De Melo, M. & Lemos, M. Distribution of collagen in the lamina propria of the human vocal fold. Laryngoscope 113, 2187\u20132191 (2003).","journal-title":"Laryngoscope"},{"key":"82157_CR89","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1097\/00005537-200312000-00027","volume":"113","author":"ECM De Melo","year":"2003","unstructured":"De Melo, E. C. M. et al. Distribution of collagen in the lamina propria of the human vocal fold. Laryngoscope 113, 2187\u20132191 (2003).","journal-title":"Laryngoscope"},{"key":"82157_CR90","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1369\/jhc.2009.954321","volume":"58","author":"L Paavilainen","year":"2010","unstructured":"Paavilainen, L. et al. The impact of tissue fixatives on morphology and antibody-based protein profiling in tissues and cells. J. Histochem. Cytochem. 58, 237\u2013246 (2010).","journal-title":"J. Histochem. Cytochem."},{"key":"82157_CR91","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/000348940211100103","volume":"111","author":"K Sato","year":"2002","unstructured":"Sato, K., Hirano, M. & Nakashima, T. Age-related changes of collagenous fibers in the human vocal fold mucosa. Ann. Otol. Rhinol. Laryngol. 111, 15\u201320 (2002).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"issue":"11","key":"82157_CR92","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1177\/000348940010901112","volume":"109","author":"K Ishii","year":"2000","unstructured":"Ishii, K., Akita, M., Yamashita, K. & Hirose, H. Age-related development of the arrangement of connective tissue fibers in the lamina propria of the human vocal fold. Ann. Otol. Rhinol. Laryngol. 109(11), 1055\u20131064 (2000).","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"82157_CR93","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/j.bpj.2011.02.015","volume":"100","author":"PJ Su","year":"2011","unstructured":"Su, P. J., Chen, W. L., Chen, Y. F. & Dong, C. Y. Determination of collagen nanostructure from second-order susceptibility tensor analysis. Biophys. J. 100, 2053\u20132062 (2011).","journal-title":"Biophys. J."},{"key":"82157_CR94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jbio.201800090","volume":"12","author":"EI Romijn","year":"2019","unstructured":"Romijn, E. I., Finn\u00f8y, A. & Lilledahl, M. B. Analyzing the feasibility of discriminating between collagen types I and II using polarization-resolved second harmonic generation. J. Biophotonics 12, 1\u201310 (2019).","journal-title":"J. Biophotonics"},{"key":"82157_CR95","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/JID.2015.399","volume":"136","author":"WCY Lo","year":"2016","unstructured":"Lo, W. C. Y. et al. Longitudinal, 3D imaging of collagen remodeling in murine hypertrophic scars in vivo using polarization-sensitive optical frequency domain imaging. J. Invest. Dermatol. 136, 84\u201392 (2016).","journal-title":"J. Invest. Dermatol."},{"key":"82157_CR96","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1364\/OPTICA.5.001329","volume":"5","author":"M Villiger","year":"2018","unstructured":"Villiger, M. et al. Optic axis mapping with catheter-based polarization-sensitive optical coherence tomography. Optica 5, 1329 (2018).","journal-title":"Optica"},{"key":"82157_CR97","first-page":"1","volume":"22","author":"J Xu","year":"2017","unstructured":"Xu, J., Song, S., Men, S. & Wang, R. K. Long ranging swept-source optical coherence tomography-based angiography outperforms its spectral-domain counterpart in imaging human skin microcirculations. J. Biomed. Opt. 22, 1 (2017).","journal-title":"J. Biomed. Opt."},{"key":"82157_CR98","doi-asserted-by":"crossref","first-page":"126007","DOI":"10.1117\/1.JBO.20.12.126007","volume":"20","author":"M Strupler","year":"2015","unstructured":"Strupler, M. et al. Toward an automated method for optical coherence tomography characterization. J. Biomed. Opt. 20, 126007 (2015).","journal-title":"J. Biomed. Opt."}],"updated-by":[{"DOI":"10.1038\/s41598-021-84391-7","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82157-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82157-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82157-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T02:34:48Z","timestamp":1670034888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82157-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,28]]},"references-count":98,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["82157"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-82157-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,28]]},"assertion":[{"value":"24 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-021-84391-7","URL":"https:\/\/doi.org\/10.1038\/s41598-021-84391-7","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2440"}}