DNTS/Russia 01/7/ 23.06.2017 “Development of new optical technologies for improvement of diagnostics quality of gastric cancer”

Funded by BSF-MES

Partners:

Institute of Electronics, Bulgarian Academy of Sciences
Federal State Budgetary Educational Organization for Higher Education Saratov National Research State University “N.G. Chernishevski” Biology Faculty, Department “Physiology of man and animals””
   
   
Institute of Electronics, Bulgarian Academy of SciencesInstitute of Electronics, Bulgarian Academy of Sciences
Saratov National Research State University “N.G. Chernishevski”
Biology Faculty, Department “Physiology of man and animals””Saratov National Research State University “N.G. Chernishevski” Biology Faculty, Department “Physiology of man and animals””
   
   
   
Scientific team
Bulgarian scientific team :
Ekaterina Borisova, Assoc. Prof., PhD – team coordinator,
Institute of Electronics, BAS
Borislav Vladimirov, Prof., D.Sci., MD
University hospital “Tsaritsa Yoanna-ISUL”
Alexander Gisbrecht, Assoc. Prof., PhD
Institute of Electronics, BAS
Tsanislava Genova-Hristova
PhD student Institute of Electronics, BAS
Liliya Angelova,
MS, Biologist , Institute of Electronics, BAS
Yana Andreeva
BS, Physicist, Institute of Electronics, BAS

 

Russian scientific team:
Oxana Semyachkina-Glushkovskaya, Prof. D. Sci.
team coordinator,
Ekaterina Zinchenko
biologist, assistant, PhD student
Arkadiy Abdurashidov
physicist, PhD student
Ilana Agranovich
biologist, PhD student
Alexander Khorovodov
biologist, student
Nikita Navolokin
clinican, assistant, PhD student
Svetlana Konnova
biologist, professor
Matvey Kanevskii
biologist, assistant
Vladimir Velikov
biologist, Assoc. prof.
Maria Ulanova
biologist, Master degree student

 

ANNOTATION:

Optical methods for detection of tissue pathologies, including malignant neoplasia are a powerful tool in the development of medical diagnostic procedures. They are characterized with a fast speed, noninvasiveness, multiple application possibilities, due to the lack of dose accumulation (such as in the case of ionizing radiation diagnostics) and objectivity. Creation, development and clinical applications of spectral techniques with diagnostic purposes is one of the main areas of biomedical photonics. This is the newest and most rapidly developing field of physical science technologies in living matter (“live sciences”). It is formed as a separate issue in the last decade and is characterized in the literature as the “revolution on the interface science – technology” (Biomedical Photonics Handbook, ISBN 0-8493-1116-0, 2003). Biophotonics is one of the priorities in the development of photonic science and technology in the European Union. In programming sessions of EC FP7 and H2020 projects were funded in this topic that shows significance of the topic, both at national and European level. That is supported in the program of the European Platform “Photonics21” as well and in its documents for strategic development of European science and industry over the next 10 years (http://www.photonics21.org/). In the current project is foreseen the application of several optical spectral methods for diagnostics and monitoring of the neoplastic changes of gastrointestinal tract tumour development, and particularly – dysplasia and neoplasia of the stomach in model systems in vivo. Combination of the interdisciplinary team of specialists in the field of physics (Bulgaria) AND BIOLOGY (Russia) will provide to the achievement of significant scientific results with the feasibility to receive data with practical value for the needs of early diagnostics and monitoring of the therapy of neoplastic changes of gastrointestinal tract (GIT).

EXPECTED RESULTS

An increased sensitivity is expected to be achieved for the fluorescence diagnostic gastroscopy of stomach and optimization of detection modes and a further application of the methods of mathematical analysis on the received spectral data for determination of non-specific inflammation, dysplastic lesions and initial development of neoplasia. Рўhe diagnostically-important parameters of oximetry, optical coherence tomography and speckle-imaging of the microcirculation of the stomach will be evaluated, which reflect changes in the condition of blood flow and vascular architecture of the organ, during the formation of the initial phases of the neoplasm development.

During the implementation of research project tasks we will develop algorithms for diagnosis and differentiation of the early stages of GIT cancer, based on optical spectral methods. New markers in blood and tissues of the organ would be identified – specific for pre-cancerous and cancerous changes. These data can be used to increase the quality of medical diagnosis for patients with gastric cancer, and conducting the early diagnosis of primary malignant changes. Model systems with the use of laboratory animals (rats, mice) will allow to study of stress-induced pathological changes in GIT. These results will provide scientific platform for a formation of new solutions for a more detailed study of the processes of carcinogenesis.

   
   
Спектрални характеристики на туморна и здрава тъкан от гастроинтестиналния тракт.Spectral characteristics of cancerous and healthy tissue from gastrointestinal tract.
Флуоресценция на абнормална гастроинтестинална тъкан.Fluorescence of abnormal gastrointestinal tissue.
   
   
   

Research contacts will be expanded between two partner organizations and up – grade of the knowledge and technical skills of both teams scientists will be achieved in the field of GIT neoplasia development. New and original experimental results for the spectral properties of different types of benign, dysplastic and malignant gastrointestinal neoplasia will be produced and their correlation with the type and stage of development, for the needs of their diagnostic and prognostic applications in clinical onco-gastroenterology. Results allowing an increase of the diagnostic accuracy are expected to be achieved, noninvasive and in real time.

Research results will be published in specialized international journals and conference proceedings, necessary for their promotion and will contribute to the overall research growth of the participants, members of the project team. Developed methodologies and algorithms will be used in the dissertation of a one PhD student for each partner, as well a Master degree thesis will be prepared from Bulgarian side for one student, as a conducted research and established cooperation will be a prerequisite for a start of another PhD studentship of this young scientist from the Bulgarian team, which will achieve a sustainable development of the IE- BAS human resources in the biophotonics research field.

PROJECT OBJECTIVES :

The main organizational objectives are related to the establishment and development of fruitful scientific research collaboration between the Institute of Electronics – BAS laboratory “Biophotonics” Bulgaria and Department “Physiology of man and animals” to Saratov National Research State University, Russian Federation, in the field of initial spectral diagnosis and monitoring of gastrointestinal (GIT) tumours. Training of young scientists and the exchange of good practices between the partners for the development and application of spectroscopic techniques in the analysis of GI pathologies in vivo is another important goal of the project.
The main research objective of this project is the development of innovative optical technologies for sensitive diagnosis of early stages of development of stomach cancer and monitoring of stress-induced appearance and development of tumors of the gastrointestinal tract by applying methods of optical spectroscopy – diffuse-reflectance spectroscopy, endogenous and exogenous fluorescence spectroscopy. The modeling of stress-induced pathologies will be monitored by optical spectroscopic methods and new scientific knowledge will be obtained, as well as there would be developed and optimized a system of discriminatory diagnostic algorithms applicable in a clinical environment.

MAIN TASKS:

To achieve this fundamental research objective we will conduct research in three main areas, incorporating a description of the stages in the conducting detailed project tasks, as follow:

  1. Carrying out of experimental studies on the optimization of the method of fluorescence gastroscopy with application of exogenous fluorophores – 5-ALA / PpIX, where we will search for an optimal concentration and effective method of administration of the drug, as well an enhancing of the quality of the optical signals based on a development of special software and mathematical analysis of the spectral data received and the development of practical recommendations for clinical application with increasing diagnostic efficiency of this fluorophore;
  2. Development and inspection of the optical techniques to diagnose primary forms of tumors of the gastrointestinal tract, in particular gastric cancer, non-invasively, without introduction of additional contrast agents by the methods of the diffuse-reflectance and autofluorescence spectroscopy of the biological tissues;
  3. Optical monitoring and examination of the mechanisms of the joint impact of bioenvironmental factors (stress, Helicobacter pillory, exotoxins in the food, water, soil and air) on the transformation of damaged areas of the stomach mucosa into malignancies for the needs of determination of methods for control and correction of the processes and development of practical recommendations for prevention of stomach cancer at risk groups.

   

Presentations under the project

  1. Macro and micro spectroscopy parameters of tumour and healthy gastrointestinal tissues, Ts. Genova, E. Borisova, O. Semyachkina-Glushkovskaya, D. Gorin, D. Bratashov, I. Terziev, Saratov Fall Meeting, Conference on Optical Technologies in Biophysics & Medicine XIX, Saratov, Russia, 25-29 September 2017, poster presentation;
  2. The role of stress and nitrosamines in the development of gatric cancer: a new model of adenocarcinoma formation with metastases in rats, A. Khorovodov, I. Agranovich, N. Shushunova, N. Navolokin, A. Telegin, A. Shnitenkova, M. Sagatova, I. Trishkina, M. Ulanova, E. Borisova, O. Semyachkina-Glushkovskaya, United European Gastroenterology Week, Barselona, Spain, 28 October-01 November 2017, poster presentation;
  3. Photodynamic diagnostics of stress-induced gastrointestinal neoplasia in laboratory animals using 5-aminolevulinic acid and Al-phthalocyanine, E. Borisova, O. Semyachkina-Glushkovskaya, N. Navolokin, I. Agranivich, A. Khorovodov, N. Shushunova, A.Bodrova., V. Mantareva., I. Angelov., I. Fedosov., A. Namykin., A. Abdurashitov., L. Avramov, PHOTONICS WEST- BiOS, January 2018, San Francisco, USA, oral presentation, Proc. SPIE 10501, Optical Diagnostics and Sensing XVIII: Toward Point-of-Care Diagnostics, 105011E (20 February 2018); doi: 10.1117/12.2289159;
  4. Feasibility study of polarization imaging and confocal fluorescence microscopy for histology analysis of soft tissue neoplasia, Ts. Genova-Hristova, T. Sang Hyuk Yoo, H. Ryung Lee, E. Borisova, E. Garcia-Caurel, R. Ossikovski, T. Novikova, O. Semyachkina-Glushkovskaya, D. Bratashov, D. Gorin, I. Terziev, Photonics Europe, 22-26 April 2018, Strasbourg, France, poster presentation;
  5. Optical UV-VIS-NIR spectroscopy of benign, dysplastic and malignant cutaneous lesions ex vivo, E. Borisova, Ts. Genova-Hristova, P. Troyanova, I. Terziev, E. Genina, A. Bashkatov, V. Tuchin, Photonics Europe, 22-26 April 2018, Strasbourg, France, poster presentation;
  6. Synchronous fluorescence spectroscopy with and without polarization sensitivity for colorectal cancer differentiation, Ts. Genova-Hristova, E. Borisova, N. Penkov, B. Vladimirov, L. Avramov, Photonics Europe, 22-26 April 2018, Strasbourg, France, oral presentation;
  7. Time-dependance of synchronous fluorescence signals in gastrointestinal tumous ex vivo, Genova-Hristova Ts., Borisova E., Penkov N., Vladimirov B., Avramov L., 5th International Symposium on Lasers in Medicine and Biophotonics, St. Petersburg, 04.06.2018 – 08.06.2018, Russian Federation, oral presentation;
  8. Fluorescence Methods for Detection of Gastrointestinal Tumours on Different Stage of Growth, E. Borisova, Ts. Genova, I. Terziev, N. Penkov, B. Vladimirov, O. Semyachkina-Glushkovskaya, L. Avramov, Current Trends in Cancer Theranostics, 01.07.2018 – 05.07.2018 Trakai, Lithuania, oral presentation;
  9. Tissue Polarimetric Discrimination Analysis of Skin and Colon Histological Samples, Deyan Ivanov, Ekaterina Borisova, Tsanislava Genova, Dimana Nazarova, Lian Nedelchev, 10th Jubilee Conference of the Balkan Physical Union, 26.08.2018 – 30.08.2018, Sofia, Bulgaria, poster presentation;
  10. Statistical Evaluation of Fluorescence Tumour Spectral Features Through Excitation-Emission Matrices for Gastrointestinal Cancer, Genova-Hristova Ts., Borisova E., Vladimirov B., Kermedchiev M., Penkov N., Avramov L., 10th Jubilee Conference of the Balkan Physical Union, 26.08.2018 – 30.08.2018, Sofia, Bulgaria, poster presentation;
  11. Stomach and intestine neoplasia fluorescence detection using 5-ala/ppix photosensitization, Agranovich I., Genova Ts., Khorovodov A., Mamedova A., Terskov A., Kanevskiy M., Shimanova V., Shitenkova A., Gisbrecht A., Avramov L., Semyachkina Glushkovskaya O., Borisova E., 20th International Conference and School on Quantum Electronics: Laser Physics and Applications, 17.09.2018 – 21.09.2018 Nessebar, Bulgaria, poster presentation;
  12. Photodetection of Stress-induced Gastrointestinal Neoplasia in Laboratorial Animals, Borisova E., Genova Ts., Khorovodov A., Agranovich I., Angelov I., Mantareva V., Kanevskiy M., Navolokin N., Semyachkina-Glushkovskaya O., Avramov L., International Conference on Advanced Laser Technologies, 17.09.2018 – 22.09.2018, Tarragona, Spain, invited lecture;
  13. Autofluorescence differentiation of lower gastrointestinal tract benign and malignant lesions using synchronous spectroscopy technique, Genova Ts., Borisova E., Penkov N., Vladimirov B., Zhelyazkova A., Avramov L., International Conference on Advanced Laser Technologies, 17.09.2018 – 22.09.2018, Tarragona, Spain, poster presentation ;
  14. Photodiagnostics of stress-induced gastrointestinal neoplasia, Borisova E., Saratov Fall Meeting 2018, 24.09.2018 – 29.09., Saratov, Russian Federation, key note lecture;
  15. Improvement of photodiagnosis using 5-ALA/PpIX, ZnPc and GalZnPc photosensitizers in combination with vaso-dilatation drugs, Khorovodov A., Borisova E., Agranovich I., Shitenkova A., Shimanova V., Kanevskiy M., Navolokin N., Genova-Hristova Ts., Angelov I., Mantareva V., Semyachkina-Glushkovskaya O., Saratov Fall Meeting 2018, 24.09.2018 – 29.09., Saratov, Russian Federation, poster presentation;
  16. Photodiagnostics of stress-induced stomach neoplasia using direct and indirect photosensitization, Khorovodov A., Agranovich I., Shintenkova A., Shimanova V., Kanevskiy M., Semyachkina-Gluyshkovskaya O., Genova Ts., Gisbrecht A., Angelov I., Mantareva V., Borisova E., Saratov Fall Meeting 2018, 24.09.2018 – 29.09., Saratov, Russian Federation, poster presentation;
  17. Fluorescence detection of 5-ALA/PpIX and Zn-Pc distribution in the body of experimental animals with stomach neoplasia, Agranovich I., Borisova E., Khorovodov A., Kanevsky M., Navolokin N., Avramov L., Angelov I., Mantareva V., Semyachkina – Glushkovskaya O., Saratov Fall Meeting 2018, 24.09.2018 – 29.09., Saratov, Russian Federation, oral presentation;
  18. Photodynamic diagnostics of stomach cancer, Agranovich I., Genova Ts., Khorovodov A., Kanevskiy M., Shimanova V., Shnitenkova A., Mantareva V., Angelov I., Semyachkina-Glushkovskaya O., Borisova E., International Conference on Laser Applications in Life Sciences, 18.11.2018 – 21.11.2018 Tel Aviv, Israel, poster presentation;
  19. Improvement of photodynamic diagnosis of gastric pre-cancer in laboratorial animals using polymer photosensitizers’ carriers, Khorovodov A., Borisova E., Agranovich I., Mantareva V., Angelov I., Meleshko T., Yakimansky Al., Navolokin N., Semyachkina-Gluyshkovskaya O., 59th Annual Conference of Indian Society of Gastroenterology, 28.11.2018 – 01.12.2018, Kochi, India, poster presentation;

Publications under the project

  1. Tsanislava Genova, Ekaterina Borisova, Oksana Semyachkina-Glushkovska, Dmitry Gorin, Daniil Bratashov, Ivan Terziev. Macro and micro spectroscopy parameters of cancerous and healthy gastrointestinal tissues. Journal of Biomedical Photonics and Engineering, 3, 4, SSAU, 2017, ISSN:2411-2844, DOI:doi: 10.18287/JBPE17.03.040305, 040305-1-040305-7 Link ;
  2. Borisova E., Genova-Hristova Ts., Penkov N., Terziev I., Troyanova P., Vladimirov B., Avramov L.. Synchronous fluorescence spectroscopy of soft tissues – tool for diagnostics of malignant lesions. IEEE Xplore, IEEE, 2018, 493-493 Link;
  3. Borisova E., Genova-Hristova Ts., Troyanova P., Terziev I., Genina E., Bashkatov A., Semyachkina -Gglushkovskaya O., Tuchin V., Avramov L.. Optical UV-VIS-NIR spectroscopy of benign, dysplastic and malignant cutaneous lesions ex vivo. Proceedings SPIE, 10685, International Society for Optics and Photonics, 2018, DOI:10.1117/12.2306914, 106853T. SJR:0.234 Link;
  4. Borisova Ekaterina, Semyachkina-Glushkovskaya O., Navolokin Nikita, Mantareva V., Angelov I., Agranovich I., Khorovodov A., Shushunova N., Bodrova A., Fedosov I., Namykin A., Abdurashidov A., Avramov L.. Photodynamic diagnostics of stress-induced gastrointestinal neoplasia in laboratory animals using 5-aminolevulinic acid and Al-phthalocyanine. Proceedings SPIE, 10501, International Society for Optics and Photonics, 2018, DOI:10.1117/12.2289159, 105011E. SJR:0.234 Link;
  5. Genova Ts., Borisova E., Penkov N., Vladimirov B., Avramov L.. Synchronous fluorescence spectroscopy with and without polarization sensitivity for colorectal cancer differentiation. Proceedings SPIE, 10685, International Society for Optics and Photonics, 2018, DOI:10.1117/12.2306877, 106852L-1-106852l-7. SJR:0.234 Link ;
  6. Genova Ts., Borisova E., Penkov N., Vladimirov B., Zhelyazkova Al., Avramov L.. Time-dependance of synchronous fluorescence signals in gastrointestinal tumours ex vivo. IEEE Xplore, IEEE, 2018, DOI:10.1109/LO.2018.8435892, 495-495 Link ;
  7. Borisova E., Gisbrecht A., Genova-Hristova Ts., Troyanova P., Pavlova E., Penkov N., Bratchenko I., Zakharov V., Lihachova I., Kuzmina I., Spigulis J.. Multispectral autoflourescence detection of skin neoplasia using steady-state techniques. Proceedings SPIE, 11047, International Society for Optics and Photonics, 2019, DOI:doi: 10.1117/12.2516337, 11047-04-6. SJR:0.234 Link;
  8. Genova Ts., Borisova E., Vladimirov B., Kermedchiev M., Penkov N., Avramov L.. Statistical evaluation of fluorescence tumour spectral features through excitationemission matrices for gastrointestinal cancer detection. AIP Conference Proceedings, 2075, 1, American Institute of Physics, 2019, DOI:10.1063/1.5091379, 170014-4. SJR:0.16 Link ;
  9. Agranovich I., Khorovodov A., Kanevskiy M., Genova -Hristova Ts., Gisbrecht A., Angelov I, Mantareva V., Navolokin N., Semyachkina – Glushkovskaya O., Borisova E.. Detection of Stress-Induced Gastrointestinal Lesions Using Al-Phthalocyanines in Experimental Animals. Proceedings SPIE, 11047, International Society for Optics and Photonics, 2019, DOI:doi: 10.1117/12.2516336, 11047-09-7. SJR:0.234 Link ;