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Project titleClinical and experimental substantiation of multiparametric optical biopsy of hepatopancreatoduodenal zone organs for minimally invasive surgical operations

AffiliationFederal State Budgetary Educational Institution of Higher Education "Orel State University named after I.S. Turgenev",

Research area 05 - FUNDAMENTAL RESEARCH IN MEDICINE, 05-602 - Physical methods of medical diagnostics. Tomography

Keywordsnon-invasive diagnostics, biomedical engineering, biophotonics, hyperspectral imaging, fluorescence spectroscopy, diffuse reflectance spectroscopy, laser speckle-contrast imaging, tissue metabolism, perfusion, biological tissue, mucous membranes, abdominal cavity, minimally invasive surgery

Annotation
Acute destructive pancreatitis (ADP) is one of the most important problems of urgent surgery of the abdominal organs. First of all, this is due to the steady incidence increase, complications frequency increase and high mortality. ADP mortality is 20-45% without differentiation of clinical forms, reaching 85% in infected pancreatic necrosis, and 100% in fulminant course of the disease. Currently, the clinic does not have clear criteria and methods of differential diagnostics of clinical and morphological forms of ADP and its postnecrotic complications. Today none of existing methods of diagnostics can not be considered by itself a completely accurate for early detection of pancreatic necrosis and its complications. A doctor has to use a complex approach in diagnostics of the disease taking into account clinical and laboratory data, ultrasound tomography, laparoscopy, radiological research methods, computer tomography and magnetic resonance imaging. There is a constant need to improve the diagnostic accuracy of procedures. In this context, the development of new methods of diagnostics in this area is highly relevant. For many years biophotonics methods are among the most effective methods of screening, diagnostics and treatment in many medical applications. The proposed project aims to develop a new integrated laser diagnostic system for the detection of pathological processes in biological tissues of the human abdominal organs. The main scientific problem of a research is express-recognition with appropriate levels of sensitivity and specificity of biological tissue areas viability sufficient for practical support of decision making by the surgeons (healthy tissue, a necrosis, an inflammation, cancer tissue) during minimally invasive surgeries with application of hyperspectral optical measurements. The ultimate goal of research is to transfer the knowledge and experience to medical institutions and industrial partners (“BIOPHOTONICS” Ltd., SPE “LAZMA” Ltd., SPE “ASTRON ELECTRONICS”). Orel State University is one of the flagship Russian universities. Since 2017, the university is implementing a strategic project “National Research & Development Center of Biomedical Photonics” and the proposed research topic is its logical continuation.

Expected results
The information obtained during the project implementation will form the basis of the construction requirements for hyperspectral imaging systems used in minimally invasive surgical operations. During the project implementation, the usage of optimal sources for fluorescence excitation, the availability of reliable imaging techniques in vivo and a qualitative interpretation of the obtained diagnostic information will allow to identify characteristics that are of prognostic importance for assessing the abdominal cavity organs state. Application of the project results will improve the diagnostic accuracy of minimally invasive surgical procedures, reduce the number of biopsies and contribute to early detection of pathology and timely organ-saving treatment. It is planned to implement the developed methodology in the industrial activity of “BIOPHOTONICS” Ltd., SPE “LAZMA” Ltd., SPE “ASTRON ELECTRONICS”. The future device is planned to be applied to the medical practice of “Orel Regional Clinical Hospital” (surgical department, in particular), as well as the Scientific Clinical Multi-field Center for Medical Care for Mothers and Children named after Z.I. Kruglaya (Orel). The results of this project are also planned to be applied to the educational process of bachelors and masters in “Biotechnical Systems and Technologies” training program. Conducting of proposed fundamental scientific research will allow obtaining and developing competencies that can further ensure the development of high-tech commercially viable medical equipment in the Russian Federation.

Annotation of the results obtained in 2020
The results obtained in 2020 include: 1. The multimodal laparoscopic system has been developed. It combines laser speckle contrast, fluorescence, and hyperspectral imaging channels. It is demonstrated that the system is sensitive to differences in the speed of liquid moving through the capillaries, as well as to the concentration of fuchsin and FAD in the phantoms developed. The implementation of the proposed methods in the rigid endoscopy system showed a high sensitivity of the measurements. 2. The original polyacrylamide-based optical phantom has been developed to verify the fluorescence measurements of flavins. This approach is characterized by polymerization processes that do not affect the fluorescence of FAD. 3. The classifier has been developed for processing multimodal data of the fluorescence spectroscopy and laser Doppler flowmetry measurement system with a fiber-optic laparoscopic probe. The results of machine learning and the proposed diagnostic parameters, especially cardiac oscillations, are of high diagnostic value and can effectively complement the analysis and classification of results obtained by fluorescence spectroscopy. 4. The high sensitivity of the multimodal approach, including fluorescence and diffuse reflectance measurements, to metabolic changes in the ischemic pancreatic tissues of laboratory animals, has been shown. 5. The algorithms for frequency analysis of laser speckle contrast imaging signals have been developed to study the spatial heterogeneity of peripheral blood flow oscillations. 6. The previously developed fine-needle optical probe system for percutaneous puncture has been tested in clinical conditions and showed high sensitivity and specificity for detecting liver cancer. 7. The implementation of the fine-needle optical probe system including measurements of fluorescence lifetime has been developed. The sensitivity of the approach to the atypical metabolic activity of malignant cells in liver cancer mouse models has been shown. 8. The software with a graphical user interface for working with experimental data when performing measurements in real-time has been developed and patented. 22 papers were published in 2020, including 9 publications indexed in Scopus and Web of Science (including a monograph published by Springer and 2 articles in Q1 journals); 2 certificates of computer program registration were obtained. The results were presented at 9 conferences, including 6 international and 3 all-Russian: SPIE Photonics West (1-6.02.2020, San Francisco, USA); the First interregional scientific and practical conference named after academician E.V. Schmidt "Engineering and computer technology in biology and medicine" (2.03.2020, Karachev); SPIE Photonics Europe Digital Forum 2020 (6-10.04.2020, Strasbourg, France); the 14th International scientific conference "Physics and Radioelectronics in Medicine and Ecology Phrеme’2020" (1-3.07.2020, Suzdal); XXIX international scientific and technical conference "Modern technologies in control, automation and information processing" (14-20. 09. 2020, Alushta); Saratov Fall Meeting 2020 (29.09-2.10.2020, Saratov); 19th international conference "Laser Optics" (ICLO 2020) (2-6.11.2020, St. Petersburg); the XVIII all-Russian youth competition-conference of scientific works on optics and laser physics (10-14. 11. 2020, Samara); the XXXIII all-Russian scientific and technical conference of students, young scientists and specialists "Biotechnical, medical and environmental systems, measuring instruments and robotic systems "(BIOMEDSYSTEMS– 2020) (9-11.12.2020, Ryazan). All the tasks and indicators announced for 2020 have been fully implemented. Information about this project (announcements, news, published articles, posters, photos of experimental research, etc.) is posted on the website of Research and Development Center of Biomedical Photonics of Orel State University, as well as on Instagram and YouTube: http://www.bmecenter.ru https://www.instagram.com/biomedical_photonics https://www.youtube.com/user/BmeCenterOrel Links to information resources on the Internet about the project: 1. The issue of the TV program “Pulse with Elena Litinskaya” “What is speckle contrast imaging and how can it help surgeons?” https://www.youtube.com/watch?v=FRo3M4zUtuo 2. Participation in the international forum SPIE Photonics Europe 2020 http://oreluniver.ru/media/news/show/1/9157 3. The device for more accurate diagnosis of cancer has been developed in Orel: https://nauka.tass.ru/nauka/8731871 4. Optical biopsy method will be used to diagnose liver cancer: https://rscf.ru/news/medicine/metod-opticheskoy-biopsii/ 5. The new method for diagnosing liver neoplasms using an optical probe has been developed: http://oreluniver.ru/media/news/show/1/9577 6. The article in top-rated journal Scientific Reports in the framework of the RSF project: http://oreluniver.ru/media/news/show/1/9516 7. The new optical probe will help detect liver cancer: https://poisknews.ru/themes/medicine/razrabotan-i-protestirovan-opticheskij-zond-kotoryj-pomozhet-effektivnee-diagnostirovat-rak-pecheni/ 8. The optical probe for liver cancer diagnosis has been developed: https://www.gazeta.ru/science/news/2020/09/16/n_14949037.shtml 9. Optical biopsy method will be used to diagnose liver cancer: https://polit.ru/news/2020/09/16/ps_rnf_optical_biopsy/ 10. The new method for diagnosing liver neoplasms using an optical probe has been developed: https://indicator.ru/medicine/razrabotan-novyi-metod-diagnostiki-novoobrazovanii-pecheni-s-pomoshyu-opticheskogo-zonda-19-09-2020.htm 11. The invention from Orel will make cancer diagnosis easier and more accurate: https://obl1.ru/reportage/orlovskoe-izobretenie-sdelaet-onkodiagnostiku-prosche-i-tochnee 12. The works on improving laparoscopy in Orel: https://www.youtube.com/watch?v=XstQH0Q9Zpc 13. Participation in the XXIV International Conference "Saratov Fall Meeting 2020" http://oreluniver.ru/media/news/show/1/9706 14. The team of Orel State University researchers has published the chapter in the book by Springer: http://oreluniver.ru/media/news/show/1/9817 15. New publication in top-rated journal “Laser Physics Letters”: http://oreluniver.ru/media/news/show/1/9908 16. Participation in the 19th international conference "Laser Optics"(ICLO 2020): http://oreluniver.ru/media/news/show/1/9931 17. Participation in the XVIII all-Russian youth competition-conference of scientific works on optics and laser physics in Samara: http://oreluniver.ru/media/news/show/1/9945 18. Participation in the international conference SPIE Photonics West 2020: http://oreluniver.ru/media/news/show/1/8876

Publications

1. Dremin V., Potapova E., Mamoshin A., Dunaev A., Rafailov E. Monitoring oxidative metabolism while modeling pancreatic ischemia in mice using a multimodal spectroscopy technique Laser Physics Letters, V. 17, № 11, 115605 (year - 2020) https://doi.org/10.1088/1612-202X/abbefa

2. Dremin V., Potapova E., Zherebtsov E., Kandurova K., Shupletsov V., Alekseyev A., Mamoshin A., Dunaev A. Optical percutaneous needle biopsy of the liver: a pilot animal and clinical study Scientific Reports, V. 10, № 1, 14200 (year - 2020) https://doi.org/10.1038/s41598-020-71089-5

3. Dunaev A. Метод и устройство оценки функционального состояния микроциркуляторно-тканевых систем организма человека на основе мультипараметрической оптической диагностики Известия вузов России. Радиоэлектроника, Т. 23, № 4. с. 77-91 (year - 2020) https://doi.org/10.32603/1993-8985-2020-23-4-77-91

4. Dunaev A.V. Принципы построения технических средств мультипараметрической оптической диагностики для оценки функционального состояния микроциркуляторно-тканевых систем Фундаментальные и прикладные проблемы техники и технологии, №6(334), с. 131-140 (year - 2020) https://doi.org/10.33979/2073-7408-2020-344-6-131-140

5. Kandurova K. Y., Shupletsov V. V., Potapova E. V., Dremin, V. V. Применение флуоресцентно-отражательной спектроскопии для задач диагностики злокачественных новообразований печени Сборник трудов XXIX Международной научно-технической конференции: Современные технологии в задачах управления, автоматики и обработки информации, с. 186–187 (year - 2020)

6. Kandurova K. Yu., Potapova E. V., Shupletsov V. V., Seryogina E. S., Dremin V. V., Zherebtsov E. A., Alekseev A. G., Mamoshin A.V., Dunaev A.V. Исследование перевитой гепатоцеллюлярной карциномы мышей методами флуоресцентной и диффузно-отражательной спектроскопии Физика и радиоэлектроника в медицине и экологии. Труды XIV Международной научной конференции ФРЭМЭ’2020, Т. 1, с. 77-81 (year - 2020)

7. Kandurova K., Potapova E., Zherebtsov E., Dremin V., Seryogina E., Vinokurov A., Mamoshin A., Borsukov A., Ivanov Yu., Dunaev A. Testing a Fine-Needle Optical Probe for Recording Changes in the Fluorescence of Coenzymes of Cellular Respiration Optics and Spectroscopy, V. 128, № 6, pp. 742–751 (year - 2020) https://doi.org/10.1134/S0030400X20060089

8. Kandurova K., Potapova E., Zherebtsov E., Dremin V., Seryogina E., Vinokurov A., Mamoshin A., Borsukov A., Ivanov Yu., Dunaev A. Апробация тонкоигольного оптического зонда для регистрации изменений флуоресценции коферментов клеточного дыхания Оптика и спектроскопия, Т. 128, № 6, с. 736-745 (year - 2020) https://doi.org/10.21883/OS.2020.06.49405.32-20

9. Mamoshin A.V., Borsukov A.V., Ivanov Yu. V. Диагностические возможности методов исследования при остром деструктивном панкреатите Медицинский алфавит, № 17, с. 26-30 (year - 2020) https://doi.org/10.33667/2078-5631-2020-17-26-30

10. Mizeva, I., Potapova, E., Kozlov, I., Dremin, V., Dunaev, A., & Krasnikov, G. Heterogeneity of cutaneous blood flow respiratory-related oscillations quantified via LSCI wavelet decomposition Proceedings of 11th Conference of the European Study Group on Cardiovascular Oscillations (ESGCO), - (year - 2020) https://doi.org/10.1109/ESGCO49734.2020.9158161

11. Potapova E., Seryogina E., Dremin V., Stavtsev D., Kozlov I., Zherebtsov E., Mamoshin A., Ivanov Yu., Dunaev A. Лазерная спекл-контрастная визуализация микроциркуляции крови в тканях поджелудочной железы при лапароскопических вмешательствах Квантовая электроника, Т. 50, № 1, с. 33-40 (year - 2020)

12. Potapova E., Seryogina E., Dremin V., Stavtsev D., Kozlov I., Zherebtsov E., Mamoshin A., Ivanov Yu., Dunaev A. Laser speckle contrast imaging of blood microcirculation in pancreatic tissues during laparoscopic interventions Quantum Electronics, V. 50, № 1, pp. 33-40 (year - 2020) https://doi.org/10.1070/QEL17207

13. Zherebtsov E., Zajnulina M., Kandurova K., Potapova E., Dremin V., Mamoshin A., Sokolovski S., Dunaev A., Rafailov E. Machine Learning Aided Photonic Diagnostic System for Minimally Invasive Optically Guided Surgery in the Hepatoduodenal Area Diagnostics, V. 10, № 11, 873 (year - 2020) https://doi.org/10.3390/diagnostics1011087

14. Potapova E., Dremin V., Zherebtsov E., Mamoshin A., Dunaev A. Multimodal Optical Diagnostic in Minimally Invasive Surgery Multimodal Optical Diagnostics of Cancer, Springer, Cham, pp. 397-424 (year - 2020) https://doi.org/10.1007/978-3-030-44594-2_11

15. Golubova N.V., Shupletsov V.V., Stavtsev D.D., Potapova E.V., Dremin V.V. Исследование возможностей многоканальной визуализации в системе жёсткой эндоскопии Биотехнические, медицинские и экологические системы, измерительные устройства и робототехнические комплексы – Биомедсистемы-2020: сб. тр. XXXIII Всерос. науч.-техн. конф. студ., мол. ученых и спец., 9-11 декабря 2020 г., с. 131-134 (year - 2020)

16. Kandurova K. Y., Shupletsov V. V., Potapova E. V. Многопараметрическая оптическая биопсия новообразований печени с использованием тонкоигольного оптического зонда диафаноскопии Сборник научных трудов I международной научно-практической конференции, Карачев, С. 32-34 (year - 2020)

17. Kandurova K., Shupletsov V., Potapova E., Zherebtsov E. Characterising hepatocellular carcinoma inoculated in mice by fluorescence lifetime measurements Saratov Fall Meeting 2020, Internet Biophotonics XIII, 1 (year - 2020)

18. Kandurova K.Y. , Shupletsov V.V., Potapova E. V., Zherebtsov E.A., Mamoshin A.V., Dunaev A.V. Измерение параметров интенсивности и времени жизни флуоресценции с использованием тонкоигольного волоконно-оптического зонда на модели гепатоцеллюлярной карциномы мышей Биотехнические, медицинские и экологические системы, измерительные устройства и робототехнические комплексы – Биомедсистемы-2020: сб. тр. XXXIII Всерос. науч.-техн. конф. студ., мол. ученых и спец., 9-11 декабря 2020 г., с. 128-131 (year - 2020)

19. Seryogina E. S., Stavtsev D. D., Dremin V. V. Применение лазерной спекл-контрастной визуализации при моделировании нарушений микроциркуляции крови в ходе лапароскопических вмешательств Сборник научных трудов I международной научно-практической конференции, Карачев, С. 35-37 (year - 2020)

20. Dremin V., Potapova E., Zherebtsov E., Kandurova K., Shupletsov V., Alekseyev A., Mamoshin A., Dunaev A. Protocol for optical percutaneous needle biopsy of the liver Protocol Exchange, pp. 1-7 (year - 2020) https://doi.org/10.21203/rs.3.pex-1126/v1

21. Piavchenko G., Seryogina E., Kandurova K., Shupletsov V., Kozlov I., Stavtsev D., Stelmashchuk O., Zherebtsov E., Dremin V., Alekseyev A., Kuznetsov S., Dunaev A., Meglinski I. Brain metabolism changes in cases of impaired breathing or blood circulation in rodents evaluated by real time optical spectroscopy methods Proceedings of SPIE Volume 11234, Optical Biopsy XVIII: Toward Real-Time Spectroscopic Imaging and Diagnosis, V. 112341, 112341E (year - 2020) https://doi.org/10.1117/12.2545708

22. Potapova E., Kandurova K., Shupletsov V., Seryogina E., Dremin V., Zherebtsov E., Alekseyev A., Mamoshin A., Ivanov Yu., Panchenkov D., Dunaev A. Optical fine needle biopsy in hepatocellular carcinoma mouse model Proceedings of SPIE Volume 11363, Tissue Optics and Photonics, V. 113630, 113630V (year - 2020) https://doi.org/10.1117/12.2555154

23. - Программный модуль контроля для спекл-контрастной визуализации в режиме реального времени -, 2020619474 (year - )

24. - Программный модуль для регистрации и сохранения данных флуоресцентной спектроскопии и спектроскопии диффузного отражения -, 2020616386 (year - )

25. - Участие в международном симпозиуме SPIE «Photonics West 2020» (Сан-Франциско, США) ОГУ имени И.С. Тургенева, - (year - )

26. - Пульс с Еленой Литинской. «Что такое спекл-контрастная визуализация, и как она может помочь хирургу?» ОГТРК, г. Орёл, - (year - )

27. - Участие в международном форуме в области фотоники и оптики SPIE Photonics Europe 2020 ОГУ имени И.С. Тургенева, - (year - )

28. - В Орле разработали устройство для более точной диагностики онкозаболеваний ТАСС Наука, - (year - )

29. - Метод оптической биопсии послужит для диагностики рака печени Российский научный фонд, - (year - )

30. - Разработан новый метод диагностики новообразований печени с помощью оптического зонда ОГУ имени И.С. Тургенева, - (year - )

31. - Статья в высокорейтинговом журнале Scientific Reports в рамках выполнения проекта РНФ ОГУ имени И.С. Тургенева, - (year - )

32. - Новый оптический зонд поможет выявлять рак печени Поиск, - (year - )

33. - Разработан оптический зонд для диагностики рака печени Газета.ru, - (year - )

34. - Метод оптической биопсии послужит для диагностики рака печени Полит.ру, - (year - )

35. - Разработан новый метод диагностики новообразований печени с помощью оптического зонда Indicator, - (year - )

36. - Орловское изобретение сделает онкодиагностику проще и точнее Телеканал «Первый областной» (г. Орёл), - (year - )

37. - В Орле работают над совершенствованием лапароскопии Телеканал «Первый областной» (г. Орёл), - (year - )

38. - Участие в XXIV международной конференции «Saratov Fall Meeting 2020» ОГУ имени И.С. Тургенева, - (year - )

39. - Коллектив ученых университета опубликовал главу в коллективной монографии издательства Springer ОГУ имени И.С. Тургенева, - (year - )

40. - Новая публикация в высокорейтинговом журнале «Laser Physics Letters» ОГУ имени И.С. Тургенева, - (year - )

41. - Участие в 19-ой международной конференции "Оптика лазеров" (ICLO 2020) ОГУ имени И.С. Тургенева, - (year - )

42. - Участие в XVIII Самарском конкурсе-конференции научных работ по оптике и лазерной физике ОГУ имени И.С. Тургенева, - (year - )

Annotation of the results obtained in 2018
The first year plan included the solution of several interrelated tasks: pectrophotometric measurements of optical properties of the abdominal cavity organs tissues; modeling the diffuse reflectance and fluorescence signals for comprehensive methodology verification and a better understanding of the obtaining measurement results as well as fitting of the experimental data; selection optimal parameters of the experimental setup; development of experimental multimodal imaging system and image processing algorithms. The following results were obtained during the first year: 1. The method and device for fluorescence spectra and laser Doppler flowmetry (LDF) measurements during percutaneous minimally invasive interventions under ultrasound and fluoroscopic control have been developed. 2. The constantly replenishing database of typical fluorescence spectra and LDF signals obtained at different levels of the biliary tract, all anatomical parts of the gallbladder and liver abscess wall has been developed. 3. The database of absorption and scattering coefficients of abdominal organs tissues in laboratory rats has been created. 4. The regularities of the relationship between the oscillating components of blood flow, registered by LDF at different levels of pressure applied to the optical probe have been revealed. The pressure influence on perfusion values and redistribution of the power of skin blood flow fluctuations at each stage of the study has been shown. Due to the phenomenon of vasodilation caused by small local pressure, the LDF signal increases at low pressure (30 mm Hg). When the pressure increases, the level of average perfusion decreases. Statistically stable amplification of endothelial blood flow oscillations under pressure of 90 mm Hg allowed us to propose the hypothesis of increasing the endothelial activity. 5. The measurements were verified by the LDF method. Significant correlation of the blood flow fluctuations and in a single human capillary and the integral assessment of perfusion obtained by LDF was established. Videolaparoscopy of blood flow observation during occlusion test showed the occurrence of reverse blood flow effect in the capillaries, which corresponds to the so-called biological zero in LDF, and should be considered in the LDF signals interpretation. 6. The diagnostic volume (radiation penetration depth) model and the model for estimating the signal-to-noise ratio of the recorded signal depending on biological tissue blood content and fiber optic probe parameters have been developed using Monte Carlo simulation and CUDA technology. 7. The model of diffuse reflectance radiation component depending on the ratio of the target chromophore concentration in epithelial tissue and taking into account the anatomical and morphological features has been developed based on Monte Carlo simulation and CUDA technology to accelerate the calculations. 8. The mathematical model of the recorded fluorescence intensity depending on the ratio of target fluorophores concentration in the epithelial tissue and taking into account its anatomical and morphological features has been developed based on the solution of the diffusion equation. 9. The algorithm for reconstruction the blood content and oxygenation maps in the surface layers of the diagnosed organ tissue from hyperspectral images by a neural network trained in the learning set obtained by Monte Carlo simulation has been developed. 10. The method for compensation of blood content influence on fluorescence intensity based on the reconstruction of blood content using previously developed neural networks trained on the learning set generated by Monte Carlo method has been developed. 11. Technical specifications and design documentation for the implementation of the multimodal experimental setup for multiparametric optical biopsy of hepatopancreatoduodenal organs during minimally invasive surgical operations have been developed. 12. The channels of hyperspectral images of fluorescence, diffuse reflectance and speckle images registration have been developed. 13. The sensitivity of speckle-contrast imaging to pancreatic ischemia in laboratory mice has been shown. 14. The selection of optimal laser sources for solving the outlined challenges has been made. 15. The channel for fluorescence lifetime measurement by a fiber-optic probe with sinusoidally modulated excitation radiation and multimode fiber for fluorescence detection supported by synchronous detection using a synchronous amplifier has been developed. 16. The sensor of the probe position under the biological tissue has been developed. 17. The saline solution channel for cleaning the probe from mucus has been developed. 18. The fluorescence-reflectance spectroscopy setup for the diagnosis of tumors during fine needle puncture-aspiration biopsy has been developed. 19. The significant differences in fluorescence and diffuse reflectance spectra of the tumor and surrounding normal tissues have been obtained in test measurements on a spontaneous rat tumor (fibrosarcoma). The areas of tissue ischemia have been revealed by the absence of oxyhemoglobin absorption peaks in the tumor spectra . According to the results of the work in 2018, 15 papers were published/accepted for publication, including 4 publications indexed in Scopus and Web of Science databases, 2 articles were sent to Q1 journals (Biomedical Optics Express, Laser Physics Letters) and 3 articles are already under review in Q1-Q2 journals (Journal of Biophotonics, Clinical Hemorheology and Microcirculation, Applied Sciences); an application for an invention was submitted. The results were presented at 5 conferences, including 4 international and 1 all-Russian: SPIE Photonics Europe, Strasbourg, France, April 22-26, 2018; 13th international scientific conference "Physics and Radioelectronics in Medicine and Ecology-FREME'2018", Vladimir – Suzdal, Russia, July 3-5, 2018; Saratov Fall Meeting 2018, Saratov, Russia, September 24-29, 2018; International Conference on Laser Applications in Life Sciences, Ramat Gan, Israel, November, 18-20 2018; XXXI all-Russian scientific and technical conference of students, young scientists and specialists "Biotechnical, medical, ecological systems and robotic complexes", Ryazan, Russia, December 4-6, 2018 All the tasks claimed in the project were fully completed, the necessary equipment was selected and purchased, 5 experimental setups were designed: to measure the fluorescence spectra and laser Doppler flowmetry signals during percutaneous minimally invasive interventions by a special fiber-optic system with a laparoscopic optical probe; to register hyperspectral images of fluorescence and diffuse reflectance; to register speckle images; to measure the fluorescence lifetime combined with fiber optic probe. Software packages for data and image processing have been developed. In 2018 the project team fulfilled the stated indicators of publication activity and staited basement for the confident work under the project in 2019. Information about this project (announcements, news, published articles, posters, photos of experimental studies, etc.) are published on the website and Instagram blog of Research and Development Center of Biomedical Photonics of Orel State University named after I.S. Turgenev at the following addresses: http://www.bmecenter.ru; https://www.instagram.com/biomedical_photonics. Links to information resources on the project on the Internet: – https://orel-region.ru/index.php?head=1&unit=12194 (Orel Region Internet Portal); – http://rscf.ru/ru/node/sotni-detey-i-vzroslykh-posetili-laboratorii-grantopoluchateley-rnf-vo-vremya-vserossiyskogo-festiva (Press Service of the Russian Science Foundation about the all-Russian event "Day without turnstiles" organized by the Russian Science Foundation and all-Russian Science Festival “NAUKA 0+”). – http://www.bmecenter.ru/ru/node/480 (about the all-Russian event "Day without turnstiles"); – https://www.youtube.com/watch?v=ush8zOHiKmk (video report about the all-Russian event "Day without turnstiles" during which visitors were told about this project).

Publications

1. Kandurova К.Y., Filina М.А., Dremin V.V., Zherebtsov Е.А., Potapova Е.V., Alyanov А.L., Mamoshin А.V., Dunaev А.V. Оптоволоконная система для интераоперационного исследования состояния органов брюшной полости при миниинвазивных хирургических вмешательствах Физика и радиоэлектроника в медицине и экологии. Труды XIII Международной научной конференции с научной молодежной школой имени И.Н. Спиридонова. В 2-х книгах., 1, 58-62 (year - 2018)

2. Kandurova К.Y., Potapova Е.V., Dunaev А.V. Флуоресцентная диагностика состояния тканей общего желчного протока при механической желтухе Биотехнические, медицинские, экологические системы и робототехнические комплексы – Биомедсистемы-2018: сб. тр. XXXI Всерос. науч.-техн. конф. студ., мол. ученых и спец., 135-138 (year - 2018)

3. Mamoshin A.V., Ivanov Y.V., Alyanov A.L., Muradyan V.F., Sumin D.S. Антеградные вмешательства при механической желтухе, обусловленной сочетанием нескольких этиологических факторов Анналы хирургической гепатологии, 23(3), 69-72 (year - 2018) https://doi.org/10.16931/1995-5464.2018369-72

4. Seryogina E.S., Stelmashchuk О.А., Piavchenko G.А., Alekseyev А.G., Vorobyev Е.V., Kuznetsova Е.А., Zherebtsov Е.А., Dunaev А.V. Оценка влияния янтарной кислоты и соединений цинка на параметры метаболизма головного мозга крыс методом флуоресцентной спектроскопии Технологии живых систем, 15(5), 37-46 (year - 2018)

5. Tarakanchikova Y.V., Stelmashchuk O.A., Seryogina E.V., Piavchenko G.A., Zherebtsov E.A., Dunaev A.V., Popov A.P., Meglinski I.V. Allocation of rhodamine-loaded nanocapsules from blood circulatory system to adjacent tissues assessed in vivo by fluorescence spectroscopy Laser Physics Letters, 15, 105601 (year - 2018) https://doi.org/10.1088/1612-202X/aad857/

6. Zherebtsov E.A., Dremin V.V., Zherebtsova A.I., Potapova E.V., Dunaev A.V. Флуоресцентная диагностика митохондриальной функции в эпителиальных тканях in vivo: монография Орел: ОГУ имени И.С. Тургенева, 107 с. (year - 2018)

7. Dremin V.V., Zherebtsov E.A., Potapova E.V., Kandurova K.Y., Mamoshin A.V., Alyanov A.L., Dunaev A.V. Optical biopsy of abdominal tissues in mini-invasive surgery International Conference on Laser Applications in Life Sciences (LALS). Track C: Treatment, - (year - 2018)

8. Kandurova K.Y., Dremin V.V., Zherebtsov E.A., Potapova E.V., Dunaev A.V., Mamoshin A.V., Alyanov A.L., Muradyan V.F. Optical diagnostics of bile duct tissues state with tumor compression Saratov Fall Meeting 2018 Symposium: Optics & Biophotonics 2018, - (year - 2018)

9. Mamoshin A.V., Alyanov A.L., Kandurova K.Y., Borsukov A.V., Ivanov Y.V., Muradyan V.F. The effectiveness of interventional procedures in patients with tumor lesion of bile ducts International Conference on Laser Applications in Life Sciences (LALS). Track C: Treatment, 32-33 (year - 2018)

10. Mamoshin А.V., Ivanov Y.V., Borsukov А.V., Alyanov А.L. Антеградные миниинвазивные вмешательства в хирургии синдрома механической желтухи Сборник тезисов «Инновационные технологии и мультидисциплинарные подходы в диагностике и лечении социально значимых заболеваний», 19-20 (year - 2018)

11. Mezentcev M.A., Potapova E.V., Shupletsov V.V., Mizeva I.A. Influence of local pressure on the oscillations of cutaneous blood flow Saratov Fall Meeting 2018 Symposium: Optics & Biophotonics 2018, - (year - 2018)

12. Seryogina E.S., Dremin V.V., Sdobnov A.Y., Kozlov I.O., Mezentsev M.A., Mamoshin A.V., Alyanov A.L., Dunaev A.V. Laser Speckle Contrast Imaging of Abdominal Organs in Rat Model Saratov Fall Meeting 2018 Symposium: Optics & Biophotonics 2018, - (year - 2018)

13. Kandurova K.Y., Dremin V.V., Zherebtsov E.A., Potapova E.V., Dunaev A.V., Mamoshin A.V., Alyanov A.L., Muradyan V.F. Application of the fluorescence spectroscopy for the analysis of the state of abdominal cavity organs tissues in mini-invasive surgery Proceedings of SPIE - The International Society for Optical Engineering, 10685,106854P (year - 2018) https://doi.org/10.1117/12.2290037

14. Kandurova K.Y., Dremin V.V., Zherebtsov E.A., Potapova E.V., Filina M.A., Dunaev A.V., Mamoshin A.V., Alyanov A.L., Muradyan V.F. Optical diagnostics of bile duct tissues state with tumor compression Proceedings of SPIE Saratov Fall Meeting 2018: Optical and Nano-Technologies for Biology and Medicine, - (year - 2019)

15. Seryogina E.S., Mezentsev M.A., Piavchenko G.A., Dremin V.V., Kozlov I.O., Sdobnov A.Y., Stelmashchuk O.A., Mamoshin A.V., Dunaev A.V. Laser Speckle Contrast Imaging of Abdominal Organs in Mouse Model Proceedings of SPIE Saratov Fall Meeting 2018: Optical and Nano-Technologies for Biology and Medicine, - (year - 2019)

16. - Научный коллектив ОГУ им. И. С. Тургенева одержал победу в конкурсе Российского научного фонда Портал Орловской области – публичный информационный центр, - (year - )

17. - «День без турникетов» в НТЦ биомедицинской фотоники Научно-технологический центр биомедицинской фотоники, - (year - )

18. - День без турникетов (Большая перемена от 15.10.2018) YouTube канал R&D Center of Biomedical Photonics, - (year - )

19. - Сотни детей и взрослых посетили лаборатории грантополучателей РНФ во время Всероссийского фестиваля науки Новостной портал РНФ, - (year - )

20. - Biomedical Photonics Center instagram, - (year - )

21. - Новости на главной странице Научно-технологический центр биомедицинской фотоники, - (year - )

Annotation of the results obtained in 2019
The following results were obtained during the reporting period: 1. An original optical phantom for verification of fluorescence measurements of flavinoids in tumors has been developed. 2. The technique of verification of fluorescence measurements in biological tissues, as well as the algorithm for images clustering into segments corresponding to different fluorescent component concentrations are developed. 3. Optical phantom for verification of speckle-contrast measurements is developed. The measurements made it possible to show that the proposed experimental system for recording speckle images combined with a commercially available laparoscope provides a qualitative and visual indication of the flow change in the capillary when modeling various velocities within the range of velocity changes in microcirculatory bed vessels. 4. The setup for measuring fluorescence lifetime in the frequency domain for obtaining fluorescence intensity and lifetime images has been improved. 5. The high sensitivity and specificity of this system (>0.8) to the presence of carcinoma areas is demonstrated. 6. The technique of pathological processes modeling in abdominal organs of laboratory animals is developed. 7. The possibility of using laser speckle contrast imaging (LSCI) technology for intraoperative monitoring of blood microcirculation in pancreatic tissue during laparoscopic intervention in laboratory animal models is shown. 8. The technique of metabolic activity registration in hepatopancreatoduodenal area tissues using fluorescence spectroscopy and imaging is developed. 9. The method of LSCI signals frequency analysis is developed. The possibility of recording the rhythms of microcirculatory blood flow using LSCI is shown. 10. The possibility of the developed experimental setup for fine-needle optical biopsy to register the metabolic activity of biological tissues using a specific modulator of cellular respiration (carbonyl cyanide m-chlorophenyl hydrazone, CCCP) was studied. 11. The ability of the developed fine-needle optical biopsy setup to register changes in fluorescence caused by metabolic changes in tissues is shown, which confirms the validity of the application of this device during fine-needle aspiration biopsy (FNAB) in clinical practice. 12. The methodology of using the original experimental setup of fine-needle optical biopsy during FNAB procedure in liver tissues has been developed. 13. A database of typical fluorescence spectra and diffuse reflectance of liver tissues and cancer tumors was developed. The database is constantly updated. In 2019 15 papers were published, including 7 publications indexed in Scopus and Web of Science, 3 of them are published in Q1 journals; 2 articles are under review; a positive decision on granting the patent of invention “Device for fluorescence and reflectance spectroscopy for the diagnosis of focal and diffuse tumors during fine-needle puncture-aspiration biopsy” is received. The results of the work were reported at 9 conferences, including 6 international and 3 all-Russian ones: SPIE Photonics West, San Francisco, USA (2-7 February 2019); II All–Russian Surgical Forum 2019, Moscow, Russia (10-12 April 2019); XI International Congress “Nevsky Radiological Forum 2019”, St. Petersburg, Russia (12-13 April 2019); Optics and Photonics International Congress 2019, OPIC2019, Yokohama, Japan, (22-26 April 2019); European Conferences on Biomedical Optics (SPIE/OSA), Munich, Germany (23-27 June 2019); VII International Symposium “Topical Problems of Biophotonics – 2019”, Nizhny Novgorod, Russia (27-31 July 2019); Saratov Fall Meeting 2019, Saratov, Russia (23-27 September 2019); XVII All-Russian Youth Samara Competition-Conference of Scientific Works on Optics and Laser Physics, Samara, Russia (12-15 November 2019); XXXIII All-Russian Scientific and Technical Conference of Students, Young Scientists and Specialists “Biotechnical, Medical, Environmental Systems and Robotic Systems”, Ryazan, Russia (4-6 December 2019). All the works planned were fully performed: the necessary equipment was selected and purchased; the phantoms for of the developed technologies verification were created; setups created in 2019 were tested using this phantoms; the phase of validation of the developed setups in model animals is almost complete; collecting of clinical data was began. In 2019, the project team completed the stated indicators of publication activity and laid the significant groundwork for 2020. Information about this project (announcements, news, published articles, posters, photos of experimental studies, etc.) are published on the website, Instagram blog and YouTube channel of Research and Development Center of Biomedical Photonics of Orel State University named after I.S. Turgenev: http://www.bmecenter.ru https://www.instagram.com/biomedical_photonics https://www.youtube.com/user/BmeCenterOrel Links to information resources on the project on the Internet: Oral talk of one of the main performers of the project (V.V. Dremin) at SPIE Photonics West 2019 on "Optical fine-needle aspiration biopsy of abdominal organs" based on the results of studies within the framework of the project: http://oreluniver.ru/media/news/show/1/7089 https://www.spiedigitallibrary.org/conference-presentations/10877/108770K/Optical-fine-needle-aspiration-biopsy-in-a-rat-model-%7C/10.1117/12.2509255?conference=Photonics_West&technology=Biomedical_Optics_&_Medical_Imaging&term=Dremin&SSO=1 Report of the TV channel “Pervy Oblastnoy” (First Regional, Orel) dedicated to the Day of Russian Science, telling about the studies at Research and Development Center of Biomedical Photonics, including this project: https://obl1.ru/sitenews/obwestvo/v-orlovskoj-oblasti-otmechayut-den-rossijskoj-nauki/ https://www.youtube.com/watch?v=iiPdxZXtW9A News about the publication of the article presenting the results of the studies supported by the project: http://www.rscf.ru/ru/node/predlozhen-novyy-metod-otsenki-sostoyaniya-sosudov?sphrase_id=33731 Poster report at the international conference “Optics and Photonics International Congress 2019” on “Complex measurements of fluorescence and speckle contrast in laboratory mice during pancreas ischemia modeling” based on the results of studies within the framework of the project: http://oreluniver.ru/media/news/show/1/7604 Report in the program “Nash Universitet” (Our University) about the studies at Research and Development Center of Biomedical Photonics, including this project: https://obl1.ru/programmy/nash-universitet/nash-universitet-14062019/ https://www.youtube.com/watch?v=XIutrWcObOg Radio program “Govorit Orel” (Orel Talks) about the research of young scientists of the Research and Development Center of Biomedical Photonics, including those working in the project: https://vk.com/wall-114302823_1293 https://www.youtube.com/watch?v=8lt56Ix20hY Poster report at the international conference “European Conference on Biomedical Optics 2019” on “Optical fine-needle biopsy approach for intraoperative multimodal diagnostics in minimally invasive abdominal surgery” based on the results of studies within the framework of the project: http://oreluniver.ru/media/news/show/1/7905 Participation in the international Symposium on Biophotonics “Topical Problems of Biophotonics-2019” with oral reports on “Optical fine-needle aspiration biopsy for mini-invasive surgery” and “Laparoscopic laser speckle contrast imaging for real-time mini-invasive surgery: animal studies” based on the results of studies within the framework of the project: http://oreluniver.ru/media/news/show/1/7987 Poster report at the XXIII international conference “Saratov Fall Meeting – 2019” on “Verification of fine needle optical probe sensitivity to changes in NADH and fad fluorescence” based on the results of studies within the framework of the project: http://oreluniver.ru/media/news/show/1/8198 Oral talk at the XVII all-Russian Youth Samara Competition-Conference of Scientific Works on Optics and Laser Physics with the Report “Application of spectroscopic methods in diagnostics of liver neoplasms” based on the results of studies within the framework of the project: http://oreluniver.ru/media/news/show/1/8520 News about the publication of the article presenting the results of the studies supported by the project: http://www.rscf.ru/ru/node/metod-otsenki-tkanevogo-krovotoka Report in the program “Puls” (Pulse) about the equipment for fine-needle optical biopsy developed within the framework of the project: https://ogtrk.ru/material.php?id=70223 https://www.youtube.com/watch?v=qQrl5kJfuI8

Publications

1. Dremin V.V, Kozlov I.O., Volkov M.V., Margaryants N.B., Potemkin A.V., Zherebtsov E.A., Dunaev A.V., Gurov I.P. Dynamic evaluation of blood flow microcirculation by combined use of the laser Doppler flowmetry and high-speed videocapillaroscopy methods Journal of Biophotonics, 12(6), e201800317 (year - 2019) https://doi.org/10.1002/jbio.201800317

2. Kandurova K.Y., Dremin V.V., Zherebtsov E.F., Potapova E.V., Alyanov A.L., Mamoshin A.V., Ivanov Y.V., Borsukov A.V., Dunaev A.V. Fiber-Optic System for Intraoperative Study of Abdominal Organs during Minimally Invasive Surgical Interventions Applied Sciences, 9(2), 217 (year - 2019) https://doi.org/10.3390/app9020217

3. Mamoshin A.V. Миниинвазивные хирургические вмешательства в диагностике и лечении острого деструктивного панкреатита Вестник новых медицинских технологий, 26(1), 42–52 (year - 2019) https://doi.org/10.24411/1609-2163-2019-16345

4. Mizeva I.A., Dremin V.V., Potapova E.V., Zherebtsov E.A., Kozlov I.O., Dunaev A.V. Wavelet Analysis of the Temporal Dynamics of the Laser Speckle Contrast in Human Skin IEEE Transactions on Biomedical Engineering, - (year - 2019) https://doi.org/10.1109/TBME.2019.2950323

5. Mizeva I.A., Potapova E.V., Dremin V.V., Zherebtsov E.A., Mezentsev M.A., Shuleptsov V.V., Dunaev A.V. Optical probe pressure effects on cutaneous blood flow Clinical Hemorheology and Microcirculation, 72(3), 259-267 (year - 2019) https://doi.org/10.3233/CH-180459

6. Borsukov A.V., Mamoshin A.V., Sumin D.S. Перкутанные малоинвазивные вмешательства в хирургии синдрома механической желтухи Лучевая диагностика и терапия, 1S, 125 (year - 2019)

7. Dremin V.V., Potapova E.V., Zherebtsov E.A., Kandurova K.Y., Shupletsov V.V., Muradyan V.F., Mamoshin A.V., Dunaev A.V. Optical fine-needle aspiration biopsy for mini-invasive surgery Proceedings of VII International Symposium "TOPICAL PROBLEMS OF BIOPHOTONICS 2019", 246-247 (year - 2019)

8. Kandurova K.Y., Seryogina E.S., Zherebtsov E.A., Potapova E.V., Dremin V.V., Vinokurov A.Y., Mamoshin A.V., Borsukov A.V., Muradyan V.F., Dunaev A.V. Verification of fine needle optical probe sensitivity to changes in NADH and FAD fluorescence Saratov Fall Meeting 2019, Optical Technologies in Biophysics & Medicine XXI, - (year - 2019)

9. Kandurova K.Y., Shupletsov V.V. Использование спектроскопических методов в диагностике новообразований печени XVII Всероссийский молодежный Самарский конкурс-конференция научных работ по оптике и лазерной физике: сборник трудов конференции, (Самара, 12–16 ноября 2019 г.), 286-293 (year - 2019)

10. Kandurova K.Y., Shupletsov V.V., Potapova E.V. Верификация канала флуоресцентной спектроскопии с применением митохондриального ингибитора Биотехнические, медицинские и экологические системы, измерительные устройства и робототехнические комплексы – Биомедсистемы-2019, сборник трудов XXXII Всерос. науч.-техн. конф. студ., мол. ученых и спец., 4-6 декабря 2019 г., 143-145 (year - 2019)

11. Mamoshin A.V., Alyanov A.L., Borsukov A.V., Muradyan V.F., Abolmasov A.V. Возможности интервенционных технологий при механической желтухе доброкачественного генеза Альманах Института хирургии им. А.В. Вишневского, 1, 353-354 (year - 2019)

12. Seryogina E.S., Kandurova K.Y., Stavtsev D.D., Shupletsov V.V., Mezentsev M.A., Kozlov I.O., Dremin V.V., Potapova E.V., Zherebtsov E.A., Mamoshin A.V., Dunaev A.V. Laparoscopic laser speckle contrast imaging for real-time mini-invasive surgery: animal studies Proceedings of VII International Symposium "TOPICAL PROBLEMS OF BIOPHOTONICS 2019", 223-224 (year - 2019)

13. Dremin V.V., Potapova E.V., Zherebtsov E.A., Kozlov I.O., Seryogina E.S., Kandurova K.Y., Alekseyev A.G., Piavchenko G.A., Kuznetsov S.L., Mamoshin A.V., Dunaev A.V. Optical fine-needle aspiration biopsy in a rat model Proceedings of SPIE Volume 10877, Dynamics and Fluctuations in Biomedical Photonics XVI, 10877, 108770K (year - 2019) https://doi.org/10.1117/12.2509255

14. Kandurova K.Y., Potapova E.V., Shupletsov V.V, Kozlov I.O., Seryogina E.S., Dremin V.V., Zherebtsov E.A., Alekseyev A.G., Mamoshin A.V., Dunaev A.V. Optical fine-needle biopsy approach for intraoperative multimodal diagnostics in minimally invasive abdominal surgery Proceedings of SPIE Volume 11079, Medical Laser Applications and Laser-Tissue Interactions IX, 11079, 110791C (year - 2019) https://doi.org/10.1117/12.2526747

15. Shupletsov V.V., Kandurova K.Y., Seryogina E.S., PiavchenkoG.A., Dremin V.V., Mamoshin A.V., Dunaev A.V. Complex measurements of fluorescence and speckle contrast in laboratory mice during pancreas ischemia modeling Proceedings of SPIE Volume 11140, Biomedical Imaging and Sensing Conference, 1114001-212 (year - 2019)

16. Mamoshin A.V., Potapova E.V., Dremin V.V., Zherebtsov E.A., Kandurova K.Y., Dunaev A.V. Устройство флуоресцентно-отражательной спектроскопии для диагностики очаговых и диффузных новообразований при проведении тонкоигольной пункционно-аспирационной биопсии -, - (year - 2019)

17. - Предложен новый метод оценки состояния сосудов Пресс-служба Российского научного фонда, - (year - )

18. - Участие в Международном симпозиуме по фотонике SPIE «Photonics West 2019» ОГУ имени И.С. Тургенева, - (year - )

19. - В Орловской области отмечают День российской науки Телеканал Первый областной, г. Орёл, - (year - )

20. - Выступление магистрантов вуза на международном конгрессе по оптике и фотонике ОГУ имени И.С. Тургенева, - (year - )

21. - Наш университет. 14.06.2019 Телеканал Первый областной, г. Орёл, - (year - )

22. - Говорит Орел (Центр биомедицинской фотоники) Государственная телевизионная и радиовещательная компания «Орёл», - (year - )

23. - Участие в международной конференции по биофотонике «European Conference on Biomedical Optics» ОГУ имени И.С. Тургенева, - (year - )

24. - Участие в международном симпозиуме по биофотонике «Topical Problems of Biophotonics – 2019» ОГУ имени И.С. Тургенева, - (year - )

25. - Студенты опорного вуза на "Saratov Fall Meeting 2019" ОГУ имени И.С. Тургенева, - (year - )

26. - Успешное выступление студентов ОГУ на конкурсе-конференции по оптике и лазерной физике в Самаре ОГУ имени И.С. Тургенева, - (year - )

27. - Ученые улучшили метод оценки тканевого кровотока Пресс-служба Российского научного фонда, - (year - )

28. - "Пульс" с Еленой Литинской. 11.12.2019 Государственная телевизионная и радиовещательная компания «Орёл», - (year - )