{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:06:35Z","timestamp":1779883595653,"version":"3.53.1"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T00:00:00Z","timestamp":1676678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP150449"],"award-info":[{"award-number":["RP150449"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["5R01CA247595"],"award-info":[{"award-number":["5R01CA247595"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cecil H. and Ida M., Green Distinguished Chair in Neuroscience","award":["RP150449"],"award-info":[{"award-number":["RP150449"]}]},{"name":"Cecil H. and Ida M., Green Distinguished Chair in Neuroscience","award":["5R01CA247595"],"award-info":[{"award-number":["5R01CA247595"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["RP150449"],"award-info":[{"award-number":["RP150449"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["5R01CA247595"],"award-info":[{"award-number":["5R01CA247595"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Depth-resolved label-free optical imaging by the method of multiphoton autofluorescence microscopy (MPAM) may offer new ways to examine cellular and extracellular atypia associated with epithelial squamous cell carcinoma (SCC). MPAM was evaluated for its ability to identify cellular and microstructural atypia in head and neck tissues from resected discarded tumor tissue. Three-dimensional image volumes were obtained from tissues from the floor of the mouth, tongue, and larynx, and were then processed for histology. MPAM micrographs were evaluated for qualitative metrics of cell atypia and quantitative measures associated with nuclear pleomorphism. Statistical analyses correlated MPAM endpoints with histological grade from each imaged site. Cellular overcrowding, discohesion, anisonucleosis, and multinucleated cells, as observed through MPAM, were found to be statistically associated with dysplasia and SCC grading, but not in histologically benign regions. A quantitative measure of the coefficient of variance in nuclear size in SCC and dysplasia was statistically elevated above histologically benign regions. MPAM also allowed for the identification of cellular heterogeneity across transitional areas and other features, such as inflammatory infiltrates. In the future, MPAM could be evaluated for the non-invasive detection of neoplasia, possibly as an adjunct to traditional conventional examination and biopsy.<\/jats:p>","DOI":"10.3390\/cancers15041302","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T01:36:37Z","timestamp":1676856997000},"page":"1302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Label-Free Imaging and Histo-Optical Evaluation of Head and Neck Cancers with Multiphoton Autofluorescence Microscopy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-7271","authenticated-orcid":false,"given":"Paula Patricia","family":"Villarreal","sequence":"first","affiliation":[{"name":"The Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Pal","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suimin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Surgical Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Coblens","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head & Neck Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5108-8637","authenticated-orcid":false,"given":"Alejandro","family":"Villasante-Tezanos","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, School for Public and Population Health, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Resto","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head & Neck Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"McCammon","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head & Neck Surgery Oncology Division, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gracie","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1016\/S0140-6736(21)01550-6","article-title":"Head and neck cancer","volume":"398","author":"Mody","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104760","DOI":"10.1016\/j.oraloncology.2020.104760","article-title":"Impact of COVID-19 on the early detection of oral cancer: A special emphasis on high risk populations","volume":"106","author":"Halboub","year":"2020","journal-title":"Oral Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1158\/1940-6207.CAPR-21-0047","article-title":"Oral Squamous Cell Carcinoma Associated with Precursor Lesions","volume":"14","author":"McCord","year":"2021","journal-title":"Cancer Prev. Res."},{"key":"ref_5","unstructured":"Canadian Cancer Society (2021, August 12). Survival Statistics for Oral Cancer. Available online: https:\/\/cancer.ca\/en\/cancer-information\/cancer-types\/oral\/prognosis-and-survival\/survival-statistics."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.pdpdt.2017.10.019","article-title":"The diagnostic value of the native fluorescence visualization device for early detection of premalignant\/malignant lesions of the oral cavity","volume":"21","author":"Amirchaghmaghi","year":"2018","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/lsm.22697","article-title":"Spectroscopic characterization of oral epithelial dysplasia and squamous cell carcinoma using multiphoton autofluorescence micro-spectroscopy","volume":"49","author":"Pal","year":"2017","journal-title":"Lasers Surg. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4637","DOI":"10.1158\/0008-5472.CAN-16-0252","article-title":"Remodeling of the Epithelial-Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging","volume":"76","author":"Pal","year":"2016","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9760","DOI":"10.1038\/s41598-018-28014-8","article-title":"In-vivo topical mucosal delivery of a fluorescent deoxy-glucose delineates neoplasia from normal in a preclinical model of oral epithelial neoplasia","volume":"8","author":"Pal","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pal, R., Yang, J., Ortiz, D., Qiu, S., Resto, V., McCammon, S., and Vargas, G. (2015). In-vivo nonlinear optical microscopy (NLOM) of epithelial-connective tissue interface (ECTI) reveals quantitative measures of neoplasia in hamster oral mucosa. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116754"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.oraloncology.2007.06.011","article-title":"Critical evaluation of diagnostic aids for the detection of oral cancer","volume":"44","author":"Lingen","year":"2008","journal-title":"Oral Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.oraloncology.2008.07.016","article-title":"Pitfalls and procedures in the histopathological diagnosis of oral and oropharyngeal squamous cell carcinoma and a review of the role of pathology in prognosis","volume":"45","author":"Woolgar","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1600-0714.2007.00582.x","article-title":"Nomenclature and classification of potentially malignant disorders of the oral mucosa","volume":"36","author":"Warnakulasuriya","year":"2007","journal-title":"J. Oral Pathol. Med."},{"key":"ref_14","first-page":"CD010173","article-title":"Clinical assessment to screen for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy adults","volume":"2013","author":"Walsh","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"040601","DOI":"10.1117\/1.JBO.27.4.040601","article-title":"In vivo microscopy as an adjunctive tool to guide detection, diagnosis, and treatment","volume":"27","author":"Bishop","year":"2022","journal-title":"J. Biomed. Opt."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.oraloncology.2008.02.002","article-title":"In vivo imaging of oral neoplasia using a miniaturized fiber optic confocal reflectance microscope","volume":"44","author":"Maitland","year":"2008","journal-title":"Oral Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.anl.2020.02.001","article-title":"Real-time imaging of head and neck squamous cell carcinomas using confocal micro-endoscopy and applicable dye: A preliminary study","volume":"47","author":"Shinohara","year":"2020","journal-title":"Auris Nasus Larynx"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1364\/BOE.5.003781","article-title":"Reflectance confocal endomicroscope with optical axial scanning for in vivo imaging of the oral mucosa","volume":"5","author":"Jabbour","year":"2014","journal-title":"Biomed. Opt. Express"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1364\/BOE.6.000524","article-title":"In vivo wide-field reflectance\/fluorescence imaging and polarization-sensitive optical coherence tomography of human oral cavity with a forward-viewing probe","volume":"6","author":"Yoon","year":"2015","journal-title":"Biomed. Opt. Express"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"014007","DOI":"10.1117\/1.2710193","article-title":"Laser confocal endomicroscopy as a novel technique for fluorescence diagnostic imaging of the oral cavity","volume":"12","author":"Thong","year":"2007","journal-title":"J. Biomed. Opt."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1517\/17530059.2010.525634","article-title":"Optical diagnostics of tissue pathology by multiphoton microscopy","volume":"4","author":"Dong","year":"2010","journal-title":"Expert Opin. Med. Diagn."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.compmedimag.2012.06.003","article-title":"Quantitative analysis of multiphoton excitation autofluorescence and second harmonic generation imaging for medical diagnosis","volume":"36","author":"Chen","year":"2012","journal-title":"Comput. Med. Imaging Graph."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Vargas, G., Shilagard, T., Ho, K.H., and McCammon, S. (2009, January 3\u20136). Multiphoton autofluorescence microscopy and second harmonic generation microscopy of oral epithelial neoplasms. Proceedings of the 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Minneapolis, MN, USA.","DOI":"10.1109\/IEMBS.2009.5332783"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1158\/0008-5472.CAN-04-3031","article-title":"Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues","volume":"65","author":"Skala","year":"2005","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"H3198","DOI":"10.1152\/ajpheart.01234.2006","article-title":"Live imaging of collagen remodeling during angiogenesis","volume":"292","author":"Kirkpatrick","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1364\/OPEX.12.002478","article-title":"In vivo multimodal nonlinear optical imaging of mucosal tissue","volume":"12","author":"Sun","year":"2004","journal-title":"Opt. Express"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4967","DOI":"10.1088\/0031-9155\/52\/16\/017","article-title":"The layered-resolved microstructure and spectroscopy of mouse oral mucosa using multiphoton microscopy","volume":"52","author":"Zhuo","year":"2007","journal-title":"Phys. Med. Biol."},{"key":"ref_28","unstructured":"Amy, T.S., and Melissa, C.S. (2015, January 7\u201312). Ex vivo label-free microscopy of head and neck cancer patient tissues. Proceedings of the SPIE, San Francisco, CA, USA."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/jbio.201100144","article-title":"Characterization of oral squamous cell carcinoma based on higher-harmonic generation microscopy","volume":"5","author":"Tsai","year":"2012","journal-title":"J. Biophotonics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1330010","DOI":"10.1142\/S1793545813300103","article-title":"Application of Multiphoton Microscopy in Dermatological Studies: A Mini-Review","volume":"7","author":"Yew","year":"2014","journal-title":"J. Innov. Opt. Health Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3389\/fphy.2020.00128","article-title":"Multiphoton Microscopy of Oral Tissues: Review","volume":"8","author":"Ardelean","year":"2020","journal-title":"Front. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e201800229","DOI":"10.1002\/jbio.201800229","article-title":"A biopsy-needle compatible varifocal multiphoton rigid probe for depth-resolved optical biopsy","volume":"12","author":"Li","year":"2019","journal-title":"J. Biophotonics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1364\/OL.29.002521","article-title":"Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective","volume":"29","author":"Kerr","year":"2004","journal-title":"Opt. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1364\/OL.381571","article-title":"Two-photon microscope using a fiber-based approach for supercontinuum generation and light delivery to a small-footprint optical head","volume":"45","author":"Zhao","year":"2020","journal-title":"Opt. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17598","DOI":"10.1073\/pnas.1114746108","article-title":"Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue","volume":"108","author":"Rivera","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12105-017-0793-2","article-title":"Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx","volume":"11","author":"Westra","year":"2017","journal-title":"Head Neck Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1364\/BOE.3.001579","article-title":"In vivo layer-resolved characterization of oral dysplasia via nonlinear optical micro-spectroscopy","volume":"3","author":"Edward","year":"2012","journal-title":"Biomed. Opt. Express"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"19494","DOI":"10.1073\/pnas.0708425104","article-title":"In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia","volume":"104","author":"Skala","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1158\/0008-5472.CAN-13-2713","article-title":"Endogenous two-photon fluorescence imaging elucidates metabolic changes related to enhanced glycolysis and glutamine consumption in precancerous epithelial tissues","volume":"74","author":"Varone","year":"2014","journal-title":"Cancer Res."},{"key":"ref_41","first-page":"62","article-title":"Basaloid Squamous cell carcinoma of oral cavity:- report of two cases","volume":"4","author":"gopinath","year":"2012","journal-title":"Int. J. Dent. Clin."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"642238","DOI":"10.3389\/froh.2021.642238","article-title":"Inflammatory Mediators in Oral Cancer: Pathogenic Mechanisms and Diagnostic Potential","volume":"2","author":"Niklander","year":"2021","journal-title":"Front. Oral Health"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S128","DOI":"10.4103\/0976-9668.166120","article-title":"Role of abnormal Langerhans cells in oral epithelial dysplasia and oral squamous cell carcinoma: A pilot study","volume":"6","author":"Rani","year":"2015","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s12105-019-01020-6","article-title":"Oral Epithelial Dysplasia and Premalignancy","volume":"13","author":"Woo","year":"2019","journal-title":"Head Neck Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.2147\/CMAR.S195470","article-title":"Multiphoton microscopy in the diagnostic assessment of pediatric solid tissue in comparison to conventional histopathology: Results of the first international online interobserver trial","volume":"11","author":"Goedeke","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ijsu.2017.10.038","article-title":"Multiphoton microscopy: A novel diagnostic method for solid tumors in a prospective pediatric oncologic cohort, an experimental study","volume":"48","author":"Muensterer","year":"2017","journal-title":"Int. J. Surg."},{"key":"ref_47","first-page":"014515","article-title":"Translation of two-photon microscopy to the clinic: Multimodal multiphoton CARS tomography of in vivo human skin","volume":"25","author":"Breunig","year":"2020","journal-title":"J. Biomed. Opt."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/jbio.200810050","article-title":"Assessing the risk of skin damage due to femtosecond laser irradiation","volume":"1","author":"Fischer","year":"2008","journal-title":"J. Biophotonics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"041320","DOI":"10.1117\/1.2960016","article-title":"Risk estimation of skin damage due to ultrashort pulsed, focused near-infrared laser irradiation at 800 nm","volume":"13","author":"Fischer","year":"2008","journal-title":"J. Biomed. Opt."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.cobme.2017.09.004","article-title":"Deep tissue imaging with multiphoton fluorescence microscopy","volume":"4","author":"Miller","year":"2017","journal-title":"Curr. Opin. Biomed. Eng."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/ijd.15152","article-title":"Features of oral squamous cell carcinoma in ex vivo fluorescence confocal microscopy","volume":"60","author":"Shavlokhova","year":"2021","journal-title":"Int. J. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e202000100","DOI":"10.1002\/jbio.202000100","article-title":"Detection of oral squamous cell carcinoma with ex vivo fluorescence confocal microscopy: Sensitivity and specificity compared to histopathology","volume":"13","author":"Shavlokhova","year":"2020","journal-title":"J. Biophotonics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1536012118808644","DOI":"10.1177\/1536012118808644","article-title":"Current Practice and Emerging Molecular Imaging Technologies in Oral Cancer Screening","volume":"17","author":"Strome","year":"2018","journal-title":"Mol. Imaging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/lsm.23090","article-title":"Feasibility of a Video-Mosaicking Approach to Extend the Field-of-View For Reflectance Confocal Microscopy in the Oral Cavity In Vivo","volume":"51","author":"Peterson","year":"2019","journal-title":"Lasers Surg. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.oraloncology.2016.01.003","article-title":"In vivo confocal microscopy for the oral cavity: Current state of the field and future potential","volume":"54","author":"Maher","year":"2016","journal-title":"Oral Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"30501","DOI":"10.1117\/1.JBO.24.3.030501","article-title":"Label-free in vivo pathology of human epithelia with a high-speed handheld dual-axis confocal microscope","volume":"24","author":"Yin","year":"2019","journal-title":"J. Biomed. Opt."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Silveyra, E., Bologna-Molina, R., G\u00f3nzalez-G\u00f3nzalez, R., and Arocena, M. (2021). The Tissue Architecture of Oral Squamous Cell Carcinoma Visualized by Staining Patterns of Wheat Germ Agglutinin and Structural Proteins Using Confocal Microscopy. Cells, 10.","DOI":"10.3390\/cells10092466"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/hed.21735","article-title":"Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope","volume":"34","author":"Muldoon","year":"2012","journal-title":"Head Neck"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Brezinski, M.E. (2006). Optical Coherence Tomography, Academic Press.","DOI":"10.1016\/B978-012133570-0\/50007-X"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/4\/1302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:36:04Z","timestamp":1760121364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/4\/1302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,18]]},"references-count":59,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["cancers15041302"],"URL":"https:\/\/doi.org\/10.3390\/cancers15041302","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,18]]}}}