{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T17:01:18Z","timestamp":1758474078278,"version":"3.41.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Artif. Intell."],"abstract":"<jats:p>Oral cancer ranks sixteenth amongst types of cancer by number of deaths. Many oral cancers are developed from potentially malignant disorders such as oral leukoplakia, whose most frequent predictor is the presence of epithelial dysplasia. Immunohistochemical staining using cell proliferation biomarkers such as ki67 is a complementary technique to improve the diagnosis and prognosis of oral leukoplakia. The cell counting of these images was traditionally done manually, which is time-consuming and not very reproducible due to intra- and inter-observer variability. The software presently available is not suitable for this task. This article presents the OralImmunoAnalyser software (registered by the University of Santiago de Compostela\u2013USC), which combines automatic image processing with a friendly graphical user interface that allows investigators to oversee and easily correct the automatically recognized cells before quantification. OralImmunoAnalyser is able to count the number of cells in three staining levels and each epithelial layer. Operating in the daily work of the Odontology Faculty, it registered a sensitivity of 64.4% and specificity of 93% for automatic cell detection, with an accuracy of 79.8% for cell classification. Although expert supervision is needed before quantification, OIA reduces the expert analysis time by 56.5% compared to manual counting, avoiding mistakes because the user can check the cells counted. Hence, the SUS questionnaire reported a mean score of 80.9, which means that the system was perceived from good to excellent. OralImmunoAnalyser is accurate, trustworthy, and easy to use in daily practice in biomedical labs. The software, for Windows and Linux, with the images used in this study, can be downloaded from <jats:ext-link>https:\/\/citius.usc.es\/transferencia\/software\/oralimmunoanalyser<\/jats:ext-link> for research purposes upon acceptance.<\/jats:p>","DOI":"10.3389\/frai.2024.1324410","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T04:45:40Z","timestamp":1708922740000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["OralImmunoAnalyser: a software tool for immunohistochemical assessment of oral leukoplakia using image segmentation and classification models"],"prefix":"10.3389","volume":"7","author":[{"given":"Zakaria A.","family":"Al-Tarawneh","sequence":"first","affiliation":[]},{"given":"Maite","family":"Pena-Crist\u00f3bal","sequence":"additional","affiliation":[]},{"given":"Eva","family":"Cernadas","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 Manuel","family":"Suarez-Pe\u00f1aranda","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Fern\u00e1ndez-Delgado","sequence":"additional","affiliation":[]},{"given":"Almoutaz","family":"Mbaidin","sequence":"additional","affiliation":[]},{"given":"Mercedes","family":"Gallas-Torreira","sequence":"additional","affiliation":[]},{"given":"Pilar","family":"G\u00e1ndara-Vila","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"114","DOI":"10.5555\/2835587.2835589","article-title":"Determining what individual SUS scores mean: adding and adjective rating scale","volume":"4","author":"Bangor","year":"2009","journal-title":"J. Usab. Stud"},{"key":"B2","first-page":"29","article-title":"SUS: a retrospective","volume":"8","author":"Brooke","year":"2013","journal-title":"J. Usab. Stud"},{"key":"B3","first-page":"249","article-title":"Assessing agreement on classification tasks: the kappa statistic","volume":"22","author":"Carletta","year":"1996","journal-title":"Comput. Linguist"},{"key":"B4","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.patcog.2016.07.002","article-title":"Influence of normalization and color space to color texture classification","volume":"61","author":"Cernadas","year":"2017","journal-title":"Pattern Recogn"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1145\/1961189.1961199","article-title":"LIBSVM: a library for support vector machines","volume":"2","author":"Chang","year":"2011","journal-title":"ACM Trans. Intel. Systs Technol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pcbi.1008337","article-title":"Cystanalyser: a new software tool for the automatic detection and quantification of cysts in polycystic kidney and liver disease, and other cystic disorders","volume":"16","author":"Cordido","year":"2020","journal-title":"PLoS Comput. Biol"},{"volume-title":"Pattern Classification","year":"2000","author":"Duda","key":"B7"},{"volume-title":"WHO Classification of Head and Neck Tumours","year":"2017","author":"El-Naggar","key":"B8"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3133","DOI":"10.5555\/2627435.2697065","article-title":"Do we need hundreds of classifiers to solve real world classification problems?","volume":"15","author":"Fern\u00e1ndez-Delgado","year":"2014","journal-title":"J. Mach. Learn. Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"105967","DOI":"10.1016\/j.oraloncology.2022.105967","article-title":"Prediction of the risk of cancer and the grade of dysplasia in leukoplakia lesions using deep learning","volume":"132","author":"Ferrer-S\u00e1nchez","year":"2022","journal-title":"Oral Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"413","DOI":"10.4317\/medoral.22326","article-title":"Survival study of leukoplakia malignant transformation in a region of northern Spain","volume":"23","author":"Gandara-Vila","year":"2018","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"B12","doi-asserted-by":"publisher","first-page":"38","DOI":"10.4103\/0975-5950.85852","article-title":"Expression of p53 protein and ki-67 antigen in oral premalignant lesions and oral squamous cell carcinomas: an immunohistochemical study","volume":"2","author":"Humayun","year":"2011","journal-title":"Natl. J. Maxillofac. Surg"},{"key":"B13","unstructured":"Lip, Oral Cavity (International Agency for Research on Cancer)2020"},{"key":"B14","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1109\/RBME.2013.2295804","article-title":"Methods for nuclei detection, segmentation, and classification in digital histopathology: a review\u2013current status and future potential","volume":"7","author":"Irshad","year":"2014","journal-title":"IEEE Rev. Biomed. Eng"},{"key":"B15","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.oraloncology.2006.03.009","article-title":"Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: an attempt to understand the sources of variation","volume":"43","author":"Kujan","year":"2007","journal-title":"Oral Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.cmpb.2017.12.014","article-title":"Immunohistochemical quantification of expression of a tight junction protein, claudin-7, in human lung cancer samples using digital image analysis method","volume":"155","author":"Lu","year":"2018","journal-title":"Comput. Meth. Prog. Biomed"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/su151813693","article-title":"Mscf: multi-scale canny filter to recognize cells in microscopic images","volume":"15","author":"Mbaidin","year":"2023","journal-title":"Sustainability"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/electronics10121432","article-title":"STERapp: semiautomatic software for stereological analysis. Application in the estimation of fish fecundity","volume":"10","author":"Mbaidin","year":"2021","journal-title":"Electronics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1476-4598-5-11","article-title":"Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions","volume":"5","author":"Mehrotra","year":"2005","journal-title":"Mol. Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e739","DOI":"10.4317\/medoral.23088","article-title":"Peri-implant peripheral giant cell lesions: report of 13 new cases and comparative histological and immunohistochemical analysis with peripheral and central giant cell lesions","volume":"24","author":"Morais","year":"2019","journal-title":"Med. Oral Patol. Oral Cirug. Bucal"},{"key":"B21","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.cmpb.2016.11.002","article-title":"Automated characterization and counting of ki-67 protein for breast cancer prognosis: a quantitative immunohistochemistry approach","volume":"139","author":"Mungle","year":"2017","journal-title":"Comput. Meth. Prog. Biomed"},{"key":"B22","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1093\/jnci\/djaa201","article-title":"Assessment of Ki67 in breast cancer: updated recommendations from the international Ki67 in Breast Cancer Working Group","volume":"113","author":"Nielsen","year":"2020","journal-title":"J. Natl. Cancer Inst"},{"key":"B23","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1109\/TSMC.1979.4310076","article-title":"A threshold selection method from gray-level histograms","volume":"9","author":"Otsu","year":"1979","journal-title":"IEEE T Syst. Man. Cyber"},{"key":"B24","article-title":"\u201cDise\u00f1o, evaluaci\u00f3n y validaci\u00f3n de un m\u00e9todo semiautom\u00e1tico para cuantificaci\u00f3n en im\u00e1genes de inmunohistoqu\u00edmica,\u201d","author":"Paravani","year":"2010","journal-title":"Congreso de m\u00e9todos num\u00e9ricos en ingenier\u00eda y ciencias aplicadas, CIMENICS'2010"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/jcm10010030","article-title":"Changes in cellular regulatory factors before and after decompression of odontogenic keratocysts","volume":"10","author":"Park","year":"2020","journal-title":"J. Clin. Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.compag.2016.04.014","article-title":"Govocitos: a software tool for estimating fish fecundity based on digital analysis of histological images","volume":"125","author":"Pintor","year":"2016","journal-title":"Comp. Electron. Agric"},{"key":"B27","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1177\/154411130301400105","article-title":"Prognosis of oral pre-malignant lesions: significance of clinical, histopathological, and molecular biological characteristics","volume":"14","author":"Reibel","year":"2003","journal-title":"Crit. Rev. Oral. Biol. Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12859-017-1934-z","article-title":"Imagej2: Imagej for the next generation of scientific image data","volume":"18","author":"Rueden","year":"2017","journal-title":"BMC Bioinformat"},{"volume-title":"A practical guide to the System Usability Scale: Background, Benchmarks","year":"2011","author":"Sauro","key":"B29"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1097\/00000478-200109000-00013","article-title":"Interpretation and quantification of immunostains","volume":"25","author":"Seidal","year":"2001","journal-title":"Am. J. Surg. Pathol"},{"volume-title":"Image Processing, Analysis, and Machine Vision","year":"2007","author":"Sonka","key":"B31"},{"key":"B32","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/0734-189X(85)90016-7","article-title":"Topological structural analysis of digitized binary images by border following","volume":"30","author":"Suzuki","year":"1985","journal-title":"Comput. Vis. Graph Image Proc"},{"key":"B33","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.oraloncology.2008.05.016","article-title":"Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management","volume":"45","author":"van der Waal","year":"2009","journal-title":"Oral Oncol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1002\/1096-9896(200107)194:3<294::AID-PATH911>3.0.CO;2-Q","article-title":"Histological grading of oral epithelial dysplasia: revisited","volume":"194","author":"Warnakulasuriya","year":"2001","journal-title":"J. Pathol"},{"key":"B35","doi-asserted-by":"publisher","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":"B36","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1111\/odi.13704","article-title":"Oral potentially malignant disorders: a consensus report from an international seminar on nomenclature and classification","volume":"27","author":"Warnakulasuriya","year":"2020","journal-title":"Oral Dis"}],"container-title":["Frontiers in Artificial Intelligence"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frai.2024.1324410\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T04:45:48Z","timestamp":1708922748000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frai.2024.1324410\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,26]]},"references-count":36,"alternative-id":["10.3389\/frai.2024.1324410"],"URL":"https:\/\/doi.org\/10.3389\/frai.2024.1324410","relation":{},"ISSN":["2624-8212"],"issn-type":[{"type":"electronic","value":"2624-8212"}],"subject":[],"published":{"date-parts":[[2024,2,26]]},"article-number":"1324410"}}