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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">N.N. Priorov Journal of Traumatology and Orthopedics</journal-id><journal-title-group><journal-title xml:lang="en">N.N. Priorov Journal of Traumatology and Orthopedics</journal-title><trans-title-group xml:lang="ru"><trans-title>Вестник травматологии и ортопедии им. Н.Н. Приорова</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0869-8678</issn><issn publication-format="electronic">2658-6738</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">626361</article-id><article-id pub-id-type="doi">10.17816/vto626361</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Original study articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Оригинальные исследования</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Neural network model development for detecting atypical mitoses in histological slides</article-title><trans-title-group xml:lang="ru"><trans-title>Разработка модели нейронной сети для выявления патологических митозов в гистологических препаратах</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7920-0552</contrib-id><contrib-id contrib-id-type="spin">3367-2493</contrib-id><name-alternatives><name xml:lang="en"><surname>Berchenko</surname><given-names>Gennadiy N.</given-names></name><name xml:lang="ru"><surname>Берченко</surname><given-names>Геннадий Николаевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Medicine), professor</p></bio><bio xml:lang="ru"><p>доктор медицинских наук, профессор, заведующий отделением, врачь-патологоанатом, цитолог</p></bio><email>berchenko@cito-bone.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0829-9188</contrib-id><contrib-id contrib-id-type="spin">5380-3194</contrib-id><name-alternatives><name xml:lang="en"><surname>Fedosova</surname><given-names>Nina V.</given-names></name><name xml:lang="ru"><surname>Федосова</surname><given-names>Нина Вениаминовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>hard_sign@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-0699-1370</contrib-id><name-alternatives><name xml:lang="en"><surname>Kochan</surname><given-names>Mikhail G.</given-names></name><name xml:lang="ru"><surname>Кочан</surname><given-names>Михаил Геннадьевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>mk_system@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-5442-5055</contrib-id><contrib-id contrib-id-type="spin">7612-1311</contrib-id><name-alternatives><name xml:lang="en"><surname>Mashoshin</surname><given-names>Dmitriy V.</given-names></name><name xml:lang="ru"><surname>Машошин</surname><given-names>Дмитрий Викторович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dima_mash@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">N.N. Priorov National Medical Research Center of Traumatology and Orthopedics</institution></aff><aff><institution xml:lang="ru">Национальный медицинский исследовательский центр травматологии и ортопедии им. Н.Н. Приорова</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2024-09-02" publication-format="electronic"><day>02</day><month>09</month><year>2024</year></pub-date><pub-date date-type="pub" iso-8601-date="2024-07-17" publication-format="electronic"><day>17</day><month>07</month><year>2024</year></pub-date><volume>31</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>337</fpage><lpage>350</lpage><history><date date-type="received" iso-8601-date="2024-02-01"><day>01</day><month>02</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2024-05-13"><day>13</day><month>05</month><year>2024</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2024, Эко-Вектор</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2025-10-09"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://journals.eco-vector.com/0869-8678/article/view/626361">https://journals.eco-vector.com/0869-8678/article/view/626361</self-uri><abstract xml:lang="en"><p><bold>Background</bold>: Modern computer systems allow digitizing and examining images of histological preparations, which led the authors to the idea of using machine learning tools in digital pathohistology. The ability of neural networks to find sub-visual image features in digitized histological preparations provides the basis for better qualitative and quantitative image analysis. Existing machine learning methods provide good accuracy and speed in recognizing various images, which gives hope for their wide application, including in oncologic diagnostics.</p> <p><bold>AIM</bold><bold>:</bold> Use methods of mathematical modeling to identify pathological mitoses in histological preparations as the main sign of the difference between malignant and benign tumor growth.</p> <p><bold>MATERIALS</bold><bold> </bold><bold>AND</bold><bold> </bold><bold>METHODS</bold><bold>: </bold>Histological images of the N.N. Priorov National Medical Research Center of Traumatology and Orthopedics were used as a data set for the neural network model. The model was tested using 188 histologic slides from 67 patients treated at the institute. Histological preparations were scanned on a Leica Aperio CS2 microscope with a ×400 resolution and converted into JPEG format with further processing. Next, the test images were analyzed in streaming mode using the created neural network model in order to obtain the coordinates of the desired diagnostic object — pathological mitosis and the probability with which the model found the object of this category. The obtained images were analyzed by a pathologist to determine whether the detected object corresponded to pathological mitosis.</p> <p><bold>RESULTS</bold><bold>: </bold>The authors have chosen an architecture, developed a methodology for training a neural network, and created a model that can be used to detect pathologic mitoses in histologic preparations. The authors do not attempt to replace the physician, but show the possibility of an integrated approach to data analysis by a computer system and a pathologist.</p> <p><bold>Conclusions</bold><bold>:</bold> The developed mathematical model of neural network used as a part of technological solution for recognizing pathological mitoses in scanned histological preparations can be used as a tool to reduce the time of research and increase the accuracy of diagnosis by a pathologist.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Обоснование.</bold> Современные компьютерные системы позволяют оцифровывать и исследовать изображения гистологических препаратов, что натолкнуло авторов на идею использования инструментов машинного обучения в цифровой патогистологии. Возможности нейронных сетей находить субвизуальные особенности изображения на оцифрованных гистологических препаратах создают основу для лучшего качественного и количественного анализа изображений. Существующие методы машинного обучения дают хорошие показатели по точности и скорости при распознавании различных изображений, что позволяет надеяться на их широкое применение, в том числе и в онкологической диагностике.</p> <p><bold>Цель.</bold> Использовать методы математического моделирования для выявления патологических митозов в гистологических препаратах как основного признака различия злокачественного и доброкачественного опухолевого процесса.</p> <p><bold>Материалы и методы.</bold> В качестве набора данных для модели нейронной сети применялись гистологические изображения НМИЦ травматологии и ортопедии им. Н.Н. Приорова. Тестирование модели выполнено с помощью 188 гистологических стёкол 67 пациентов, проходивших лечение в институте. Гистологические препараты были отсканированы на микроскопе Leica Aperio CS2 с разрешением ×400 и преобразованы в формат JPEG с последующей обработкой. Далее в потоковом режиме был выполнен анализ тестовых изображений с использованием созданной модели нейронной сети с целью получения координат искомого объекта диагностики — патологического митоза и вероятности, с которой модель находила объект данной категории. Полученные изображения были проанализированы врачом-патологоанатомом на предмет соответствия выявленного объекта патологическому митозу.</p> <p><bold>Результаты.</bold> Авторы выбрали архитектуру, разработали методологию обучения нейронной сети и создали модель, которую можно использовать для обнаружения патологических митозов в гистологических препаратах. Авторы не пытаются заменить врача, а показывают возможность комплексного подхода к анализу данных компьютерной системой и врачом-патологоанатомом.</p> <p><bold>Заключение.</bold> Разработанная математическая модель нейронной сети, используемая в составе технологического решения для распознавания патологических митозов в отсканированных гистологических препаратах, может применяться как инструмент для сокращения времени исследования и повышения точности диагностики врача-патологоанатома.</p></trans-abstract><kwd-group xml:lang="en"><kwd>neural network</kwd><kwd>mathematical model</kwd><kwd>artificial intelligence</kwd><kwd>tumor</kwd><kwd>pathological mitosis</kwd><kwd>machine learning</kwd><kwd>bone pathology</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>нейронная сеть</kwd><kwd>математическая модель</kwd><kwd>искусственный интеллект</kwd><kwd>опухоль</kwd><kwd>патологический митоз</kwd><kwd>машинное обучение</kwd><kwd>костная патология</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Госзадание по научно-исследовательской работе, РК</institution></institution-wrap><institution-wrap><institution xml:lang="en">State assignment for scientific research work, RK</institution></institution-wrap></funding-source><award-id>124040100041-5</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Dorfman HD, Czerniak B. Bone tumors. 2nd edition. St. Louis: Mosby; 2015. 1261 p.</mixed-citation><mixed-citation xml:lang="ru">Dorfman H.D., Czerniak B. Bone tumors. 2nd edition. St. Louis: Mosby, 2015. 1261 p.</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">Girshick R. Fast R-CNN. In: IEEE International Conference on Computer Vision (ICCV); 2015.</mixed-citation><mixed-citation xml:lang="ru">Girshick R. Fast R-CNN. In: IEEE International Conference on Computer Vision (ICCV), 2015.</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">Ren S, He K, Girshick R, Sun J. Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks. IEEE Trans Pattern Anal Mach Intell. 2017;9(6):1137–1149. doi: 10.1109/TPAMI.2016.2577031</mixed-citation><mixed-citation xml:lang="ru">Ren S., He K., Girshick R., Sun J. Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks // IEEE Trans Pattern Anal Mach Intell. 2017. Vol. 39, № 6. Р. 1137–1149. doi: 10.1109/TPAMI.2016.2577031</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">Ren S, He K, Girshick R, Zhang X, Sun J. Object Detection Networks on Convolutional Feature Maps. IEEE Trans Pattern Anal Mach Intell. 2017;39(7):1476–1481. doi: 10.1109/TPAMI.2016.2601099</mixed-citation><mixed-citation xml:lang="ru">Ren S., He K., Girshick R., Zhang X., Sun J. Object Detection Networks on Convolutional Feature Maps // IEEE Trans Pattern Anal Mach Intell. 2017. Vol. 39, № 7. Р. 1476–1481. doi: 10.1109/TPAMI.2016.2601099</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">Lin T-Y, Dollár P, Girshick R, He K, Hariharan B, Belongie S. Feature Pyramid Networks for Object Detection, Computer Science &gt; Computer Vision and Pattern Recognition [Submitted on 9 Dec 2016 (v1), last revised 19 Apr 2017 (this version, v2)]. Available from: https://arxiv.org/abs/1612.03144</mixed-citation><mixed-citation xml:lang="ru">Lin T-Y., Dollár P., Girshick R., He K., Hariharan B., Belongie S. Feature Pyramid Networks for Object Detection, Computer Science &gt; Computer Vision and Pattern Recognition [Submitted on 9 Dec 2016 (v1), last revised 19 Apr 2017 (this version, v2)]. Режим доступа: https://arxiv.org/abs/1612.03144</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">Girshick R, Donahue J, Darrell T, Malik J. Rich feature hierarchies for accurate object detection and semantic segmentation. In: CVPR; 2014. arXiv: 1311.2524.</mixed-citation><mixed-citation xml:lang="ru">Girshick R., Donahue J., Darrell T., Malik J. Rich feature hierarchies for accurate object detection and semantic segmentation. In: CVPR, 2014. arXiv: 1311.2524.</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">Girshick R, Donahue J, Darrell T, Malik J. Region-Based Convolutional Networks for Accurate Object Detection and Segmentation. IEEE Trans Pattern Anal Mach Intell. 2016;38(1):142–58. doi: 10.1109/TPAMI.2015.2437384</mixed-citation><mixed-citation xml:lang="ru">Girshick R., Donahue J., Darrell T., Malik J. Region-Based Convolutional Networks for Accurate Object Detection and Segmentation // IEEE Trans Pattern Anal Mach Intell. 2016. Vol. 38, № 1. Р. 142–58. doi: 10.1109/TPAMI.2015.2437384</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">Uijlings J, van de Sande K, Gevers T, Smeulders A. Selective search for object recognition. International Journal of Computer Vision. 2013;104(2):154–171. doi: 10.1007/s11263-013-0620-5</mixed-citation><mixed-citation xml:lang="ru">Uijlings J., van de Sande K., Gevers T., Smeulders A. Selective search for object recognition // International Journal of Computer Vision. 2013. Vol. 104, № 2. P. 154–171. doi: 10.1007/s11263-013-0620-5</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><citation-alternatives><mixed-citation xml:lang="en">He K, Gkioxari G, Dollar P, Girshick R. Mask R-CNN. IEEE Trans Pattern Anal Mach Intell. 2020;42(2):386–397. doi: 10.1109/TPAMI.2018.2844175</mixed-citation><mixed-citation xml:lang="ru">He K., Gkioxari G., Dollar P., Girshick R., Mask R-CNN // IEEE Trans Pattern Anal Mach Intell. 2020. Vol. 42, № 2. Р. 386–397. doi: 10.1109/TPAMI.2018.2844175</mixed-citation></citation-alternatives></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">Detectron [Internet]. Available from: https://github.com/facebookresearch/Detectron</mixed-citation><mixed-citation xml:lang="ru">Detectron [Интернет]. Режим доступа: https://github.com/facebookresearch/Detectron</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">Pantanowitz L, Quiroga-Garza GM, BienRonen L, et al. An artificial intelligence algorithm for prostate cancer diagnosis in whole slide images of core needle biopsies: a blinded clinical validation and deployment study. Lancet Digital Health. 2020;2(8):e407–e416. doi: 10.1016/S2589-7500(20)30159-X</mixed-citation><mixed-citation xml:lang="ru">Pantanowitz L., Quiroga-Garza G.M., BienRonen L., et al. An artificial intelligence algorithm for prostate cancer diagnosis in whole slide images of core needle biopsies: a blinded clinical validation and deployment study // Lancet Digital Health. 2020. Vol. 2, № 8. Р. e407–e416. doi: 10.1016/S2589-7500(20)30159-X</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">Pantanowitz L, Hartman D, Yan Qi, Eun Yoon Cho, et al. Accuracy and efficiency of an artificial intelligence tool when counting breast mitoses. Diagn Pathol. 2020;15(1):80. doi: 10.1186/s13000-020-00995-z</mixed-citation><mixed-citation xml:lang="ru">Pantanowitz L., Hartman D., Yan Qi, Eun Yoon Cho, et al. Accuracy and efficiency of an artificial intelligence tool when counting breast mitoses // Diagn Pathol. 2020. Vol. 15, № 1. Р. 80. doi: 10.1186/s13000-020-00995-z</mixed-citation></citation-alternatives></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">Van EttenIn A. Satellite Imagery Multiscale Rapid Detection with Windowed Networks. arXiv: 1809.09978v1. Available from: https://arxiv.org/pdf/1809.09978.pdf</mixed-citation><mixed-citation xml:lang="ru">Van EttenIn A. Satellite Imagery Multiscale Rapid Detection with Windowed Networks. arXiv: 1809.09978v1. Режим доступа: https://arxiv.org/pdf/1809.09978.pdf</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">Simonyan K, Zisserman A. Very deep convolutional networks for large-scale image recognition. 10 Apr 2015. arXiv: 1409.1556. Available from: https://arxiv.org/pdf/1409.1556.pdf</mixed-citation><mixed-citation xml:lang="ru">Simonyan K., Zisserman A. Very deep convolutional networks for large-scale image recognition. 10 Apr 2015. arXiv: 1409.1556. Режим доступа: https://arxiv.org/pdf/1409.1556.pdf</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">Barisonia L, Hodgin JB. Digital pathology in nephrology clinical trials, research, and pathology practice. Curr Opin Nephrol Hypertens. 2017;26(6):450–459. doi: 10.1097/MNH.0000000000000360</mixed-citation><mixed-citation xml:lang="ru">Barisonia L., Hodgin J.B. Digital pathology in nephrology clinical trials, research, and pathology practice // Curr Opin Nephrol Hypertens. 2017. Vol. 26, № 6. Р. 450–459. doi: 10.1097/MNH.0000000000000360</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">Burt JR, Torosdagli N, Khosravan N, et al. Deep learning beyond cats and dogs: recent advances in diagnosing breast cancer with deep neural networks. Br J Radiol. 2018;91(1089):20170545. doi: 10.1259/bjr.20170545</mixed-citation><mixed-citation xml:lang="ru">Burt J.R., Torosdagli N., Khosravan N., et al. Deep learning beyond cats and dogs: recent advances in diagnosing breast cancer with deep neural networks // Br J Radiol. 2018. Vol. 91, № 1089. Р. 20170545. doi: 10.1259/bjr.20170545</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><citation-alternatives><mixed-citation xml:lang="en">Mermel C, Kunal Nagpal MS. Using AI to identify the aggressiveness of prostate cancer. Google Health. 2020. Available from: https://blog.google/technology/health/using-ai-identify-aggressiveness-prostate-cancer</mixed-citation><mixed-citation xml:lang="ru">Mermel C., Kunal Nagpal M.S. Using AI to identify the aggressiveness of prostate cancer // Google Health. 2020. Режим доступа: https://blog.google/technology/health/using-ai-identify-aggressiveness-prostate-cancer</mixed-citation></citation-alternatives></ref><ref id="B18"><label>18.</label><citation-alternatives><mixed-citation xml:lang="en">Nagpal K, Foote D, Tan F, et al. Development and Validation of a Deep Learning Algorithm for Gleason Grading of Prostate Cancer from Biopsy Specimens. JAMA Oncol. 2020;6(9):1–9. doi: 10.1001/jamaoncol.2020.2485</mixed-citation><mixed-citation xml:lang="ru">Nagpal K., Foote D., Tan F., et al. Development and Validation of a Deep Learning Algorithm for Gleason Grading of Prostate Cancer from Biopsy Specimens // JAMA Oncol. 2020. Vol. 6, № 9. Р. 1–9. doi: 10.1001/jamaoncol.2020.2485</mixed-citation></citation-alternatives></ref></ref-list></back></article>
