{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:00:30Z","timestamp":1785873630915,"version":"3.56.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1822\/12"],"award-info":[{"award-number":["1822\/12"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accurate diagnosis of oral soft tissue lesions is critical for effective treatment, yet conventional histopathological examination, the gold standard, faces limitations. These include two-dimensional (2D) visualization and malorientation, which can obscure critical diagnostic features, like epithelial-connective tissue interfaces. Micro-computed tomography (\u00b5CT) offers a non-destructive, high-resolution three-dimensional (3D) imaging alternative to address these challenges. Still, its use for soft tissue visualization is limited. We tested a method with specific radio-opaque staining and \u00b5CT scanning settings to visualize oral soft tissue biopsies as a proof of concept.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Biopsies from 12 patients with different oral mucosa lesions were stained with Lugol\u2019s iodine, scanned at 3\u00b5m resolution with 70kV energy, and the resulting volumes were compared to histopathological sections by specialists in oral radiology and oral pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\u00b5CT produced 2D images with tissue architecture comparable to hematoxylin and eosin (H&amp;E)-stained sections, distinguishing epithelium, connective tissue, and keratin, while 3D reconstructions revealed topographic details, such as ulceration depth and vascular patterns, unattainable in histopathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings highlight \u00b5CT potential as a complementary diagnostic tool, enhancing topographic rendering while preserving tissue integrity. Standardized protocols and broader validation, particularly for precancerous and malignant lesions, are essential for clinical adoption, promising improved diagnostic accuracy in oral pathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0335602","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T17:28:56Z","timestamp":1761931736000},"page":"e0335602","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Micro-Computed Tomography as a complementary tool for histopathological diagnosis of oral soft tissue lesions \u2013 Proof of 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Ramsay","year":"1999","journal-title":"Histopathology"},{"key":"pone.0335602.ref002","first-page":"354","article-title":"Epithelial pathology","volume-title":"Oral and maxillofacial pathology","author":"BW Neville","year":"2024"},{"key":"pone.0335602.ref003","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.oraloncology.2008.06.002","article-title":"Global epidemiology of oral and oropharyngeal cancer","volume":"45","author":"S Warnakulasuriya","year":"2009","journal-title":"Oral Oncol"},{"issue":"9","key":"pone.0335602.ref004","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1034\/j.1600-0714.2003.00125.x","article-title":"Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications","volume":"32","author":"EH van der Meij","year":"2003","journal-title":"J Oral Pathol Med"},{"key":"pone.0335602.ref005","first-page":"264","article-title":"Oral cavity and mobile tongue tumours.","volume-title":"WHO Classification of Head and Neck Tumours","year":"2024"},{"key":"pone.0335602.ref006","first-page":"37","article-title":"Special techniques in surgical pathology","year":"2011","journal-title":"Rosai and Ackerman\u2019s Surgical Pathology"},{"issue":"5","key":"pone.0335602.ref007","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1097\/PAP.0b013e318229bf20","article-title":"Study of amended reports to evaluate and improve surgical pathology processes","volume":"18","author":"FA Meier","year":"2011","journal-title":"Adv Anat Pathol"},{"key":"pone.0335602.ref008","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-3-642-60592-5_2","article-title":"Histological typing of cancer and precancer of the oral mucosa","volume-title":"Histological typing of cancer and precancer of the oral mucosa","author":"JJ Pindborg","year":"1997"},{"issue":"9","key":"pone.0335602.ref009","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1136\/jcp.56.9.677","article-title":"Visualising scanning patterns of pathologists in the grading of cervical intraepithelial neoplasia","volume":"56","author":"ESM Tiersma","year":"2003","journal-title":"J Clin Pathol"},{"issue":"10","key":"pone.0335602.ref010","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.5858\/2005-129-1237-EDIAP","article-title":"Error detection in anatomic pathology","volume":"129","author":"RJ Zarbo","year":"2005","journal-title":"Arch Pathol Lab Med"},{"issue":"3","key":"pone.0335602.ref011","first-page":"139","article-title":"Quality in cancer diagnosis","volume":"60","author":"SS Raab","year":"2010","journal-title":"CA Cancer J Clin"},{"issue":"4","key":"pone.0335602.ref012","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1200\/JOP.2013.001204","article-title":"Second-opinion pathologic review is a patient safety mechanism that helps reduce error and decrease waste","volume":"10","author":"LP Middleton","year":"2014","journal-title":"J Oncol Pract"},{"issue":"1","key":"pone.0335602.ref013","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1365-2559.2009.03325.x","article-title":"Tracking with virtual slides: a tool to study diagnostic error in histopathology","volume":"55","author":"D Treanor","year":"2009","journal-title":"Histopathology"},{"issue":"9","key":"pone.0335602.ref014","first-page":"11884","article-title":"Essentials of oral cancer","volume":"8","author":"C Rivera","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"pone.0335602.ref015","doi-asserted-by":"crossref","DOI":"10.1596\/978-1-4648-0349-9_ch5","article-title":"Oral cancer: prevention, early detection, and treatment.","volume-title":"Cancer: disease control priorities, third edition (volume 3)","author":"R Sankaranarayanan","year":"2015"},{"key":"pone.0335602.ref016","first-page":"422","article-title":"Head and neck cancers.","volume-title":"World Cancer Report 2014","author":"LDR Thompson","year":"2014"},{"issue":"815","key":"pone.0335602.ref017","article-title":"Computerized transverse axial scanning (tomography): Part I. Description of system. 1973","volume":"68","author":"GN Hounsfield","year":"1995","journal-title":"Br J Radiol"},{"key":"pone.0335602.ref018","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev-bioeng-071910-124717","article-title":"Current status of developments and applications of micro-CT","volume":"13","author":"EL Ritman","year":"2011","journal-title":"Annu Rev Biomed Eng"},{"issue":"1075","key":"pone.0335602.ref019","doi-asserted-by":"crossref","first-page":"20170113","DOI":"10.1259\/bjr.20170113","article-title":"Early clinical applications for imaging at microscopic detail: microfocus computed tomography (micro-CT)","volume":"90","author":"JC Hutchinson","year":"2017","journal-title":"Br J Radiol"},{"key":"pone.0335602.ref020","article-title":"Computed tomography: fundamentals, system technology, image quality, applications","author":"WA Kalender","year":"2011"},{"key":"pone.0335602.ref021","doi-asserted-by":"crossref","first-page":"14088","DOI":"10.1038\/srep14088","article-title":"Three-dimensional non-destructive soft-tissue visualization with X-ray staining micro-tomography","volume":"5","author":"JM de S e Silva","year":"2015","journal-title":"Sci Rep"},{"key":"pone.0335602.ref022","first-page":"25","article-title":"PACS and imaging informatics: Basic principles and applications.","volume-title":"PACS and imaging informatics: Basic principles and applications","author":"JS Walker","year":"2010"},{"issue":"1","key":"pone.0335602.ref023","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jdent.2011.09.002","article-title":"Validity of MicroCT for in vitro detection of proximal carious lesions in primary molars","volume":"40","author":"VM Soviero","year":"2012","journal-title":"J Dent"},{"issue":"1","key":"pone.0335602.ref024","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1590\/1678-775720150293","article-title":"Impact of micronutrients supplementation on bone repair around implants: microCT and counter-torque analysis in rats","volume":"24","author":"SP Pimentel","year":"2016","journal-title":"J Appl Oral Sci"},{"issue":"10","key":"pone.0335602.ref025","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1007\/s00330-009-1434-2","article-title":"Molecular imaging by micro-CT: specific E-selectin imaging","volume":"19","author":"C Wyss","year":"2009","journal-title":"Eur Radiol"},{"issue":"9","key":"pone.0335602.ref026","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3390\/jimaging7090172","article-title":"Micro-CT for Biological and Biomedical Studies: A Comparison of Imaging Techniques","volume":"7","author":"K Keklikoglou","year":"2021","journal-title":"J Imaging"},{"issue":"3","key":"pone.0335602.ref027","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1162\/1535350042380326","article-title":"Small-animal X-ray dose from micro-CT","volume":"3","author":"JM Boone","year":"2004","journal-title":"Mol Imaging"},{"key":"pone.0335602.ref028","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1472-6793-9-11","article-title":"MicroCT for comparative morphology: simple staining methods allow high-contrast 3D imaging of diverse non-mineralized animal tissues","volume":"9","author":"BD Metscher","year":"2009","journal-title":"BMC Physiol"},{"issue":"3","key":"pone.0335602.ref029","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1161\/CIRCIMAGING.109.918482","article-title":"Rapid 3D phenotyping of cardiovascular development in mouse embryos by micro-CT with iodine staining","volume":"3","author":"K Degenhardt","year":"2010","journal-title":"Circ Cardiovasc Imaging"},{"issue":"3","key":"pone.0335602.ref030","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/dvdy.21857","article-title":"MicroCT for developmental biology: a versatile tool for high-contrast 3D imaging at histological resolutions","volume":"238","author":"BD Metscher","year":"2009","journal-title":"Dev Dyn"},{"issue":"3","key":"pone.0335602.ref031","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/jez.b.22561","article-title":"Iodine-enhanced micro-CT imaging: methodological refinements for the study of the soft-tissue anatomy of post-embryonic vertebrates","volume":"322","author":"PM Gignac","year":"2014","journal-title":"J Exp Zool B Mol Dev Evol"},{"key":"pone.0335602.ref032","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-4-431-76933-0_6","article-title":"Using CT to peer into the past: 3D visualization of the brain and ear regions of birds, crocodiles, and nonavian dinosaurs in anatomical imaging: Towards a new morphology.","volume-title":"Anatomical imaging: Towards a new morphology","author":"LM Witmer","year":"2008"},{"key":"pone.0335602.ref033","first-page":"105","article-title":"Bancroft\u2019s theory and practice of histological techniques.","volume-title":"Bancroft\u2019s theory and practice of histological techniques","author":"LT Spencer","year":"2013"},{"issue":"8","key":"pone.0335602.ref034","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/jso.21021","article-title":"Staging of head and neck cancers: is it time to change the balance between the ideal and the practical?","volume":"97","author":"SG Patel","year":"2008","journal-title":"J Surg Oncol"},{"issue":"8","key":"pone.0335602.ref035","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.humpath.2009.04.006","article-title":"Overview of telepathology, virtual microscopy, and whole slide imaging: prospects for the future","volume":"40","author":"RS Weinstein","year":"2009","journal-title":"Hum Pathol"},{"issue":"1","key":"pone.0335602.ref036","doi-asserted-by":"crossref","first-page":"28237","DOI":"10.1038\/s41598-024-79060-4","article-title":"Micro-computed Tomography in the Evaluation of Eosin-stained Axillary Lymph Node Biopsies of Females Diagnosed with Breast Cancer","volume":"14","author":"S Laguna-Castro","year":"2024","journal-title":"Sci Rep"},{"key":"pone.0335602.ref037","article-title":"Three-dimensional measurement of the depth of invasion in oral squamous cell carcinoma samples using Lugol\u2019s iodine-enhanced micro-computed tomography: an original study","volume":"33","author":"J Yu","year":"2025","journal-title":"J Appl Oral Sci"},{"issue":"4","key":"pone.0335602.ref038","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cden.2008.05.005","article-title":"What is cone-beam CT and how does it work?","volume":"52","author":"WC Scarfe","year":"2008","journal-title":"Dent Clin North 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Med"},{"key":"pone.0335602.ref042","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.media.2017.07.005","article-title":"A survey on deep learning in medical image analysis","volume":"42","author":"G Litjens","year":"2017","journal-title":"Med Image Anal"},{"key":"pone.0335602.ref043","first-page":"207","volume-title":"The essential physics of medical imaging. In: Bushberg JT, Seibert JA, Leidholdt EM, Boone JM","year":"2012"},{"issue":"5","key":"pone.0335602.ref044","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.3758\/APP.72.5.1205","article-title":"Current perspectives in medical image perception","volume":"72","author":"EA Krupinski","year":"2010","journal-title":"Atten Percept Psychophys"},{"issue":"1","key":"pone.0335602.ref045","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.media.2007.06.005","article-title":"Non-rigid registration of multi-modal images using both mutual information and cross-correlation","volume":"12","author":"A Andronache","year":"2008","journal-title":"Med Image Anal"},{"issue":"1","key":"pone.0335602.ref046","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.tripleo.2008.03.018","article-title":"Comparative dosimetry of dental CBCT devices and 64-slice CT for oral and maxillofacial radiology","volume":"106","author":"JB Ludlow","year":"2008","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T17:29:04Z","timestamp":1761931744000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335602"}},"subtitle":[],"editor":[{"given":"Ronell","family":"Bologna-Molina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0335602","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]}}}