biophBiomedical PhotonicsBiomedical Photonics2413-9432Non-profit partnership for development of domestic photodynamic therapy and photodiagnosis10.24931/2413-9432-2023-12-2-16-23bioph-591Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПрименение видеокапилляроскопии для мониторинга микроциркуляции в коже при фотодинамической терапииVideocapillaroscopic monitoring of microcirculation in rats during photodynamic therapyГурылеваА. В.GurylevaA. V.

Москва

Moscow

МачихинА. С.MachikhinA. S.

Москва

Moscow

ГришачеваТ. Г.GrishachevaT. G.

Санкт-Петербург

St. Petersburg

tgrishacheva@gmail.comПетрищевН. Н.PetrishchevN. N.

Санкт-Петербург

St. Petersburg

Научно-технологический центр уникального приборостроения Российской академии наукРоссияScientific and Technological Center for Unique Instrumentation of the Russian Academy of SciencesRussian FederationПервый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияFirst St. Petersburg State Medical University named after Academician I.P. PavlovaRussian Federation20232108202312216–23Copyright © Гурылева А.В., Мачихин А.С., Гришачева Т.Г., Петрищев Н.Н., 20232023Гурылева А.В., Мачихин А.С., Гришачева Т.Г., Петрищев Н.Н.Guryleva A.V., Machikhin A.S., Grishacheva T.G., Petrishchev N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pdt-journal.com/jour/article/view/591

Предложено аппаратно-программное и методическое обеспечение для оценки микроциркуляции, которое отличается неинвазивностью, информативностью, а главное, возможностью проводить исследование в ходе фотоактивации, и может стать дополнением к существующим диагностическим методам как в исследовательских задачах, так и в клинической практике. Выявленные с помощью разработанного подхода функциональные принципы реакции сосудистой сети на фотодинамическое воздействие представляются полезными для повышения эффективности и безопасности фотодинамической терапии. Разработка и апробация методов видеокапилляроскопии и фотоплетизмографии для изучения ранних изменений микроциркуляции при фотодинамической активации. Разработанная установка позволяет одновременно проводить фотодинамическое воздействие и исследование параметров микроциркуляции методами видеокапилляроскопии и фотоплетизмографии. Фотодинамическое воздействие осуществляется через 3 ч после внутривенного введения фотосенсибилизатора на основе хлорина е6 (5 мг/кг) лазерным излучением с длиной волны 662 нм и плотностью мощности 15 мВт/см2  в непрерывном и импульсном режимах. Визуализирующая система установки состоит из микроскопа с большим рабочим расстоянием, цифровой высокоскоростной камеры и оптического фильтра, отрезающего отраженное от исследуемой поверхности излучение фотоактивации. Осветительная система представлена диодным источником излучения с центральной длиной волны 532 нм. Зарегистрированные установкой изображения исследуемого участка кожи обрабатываются в разработанном авторами программном обеспечении для получения морфометрических и гемодинамических данных о микроциркуляции. Для сравнения предложенного подхода с существующими методами параметры кровотока регистрировали также лазерным доплеровским флоуметром. В ходе апробации разработанной установки на инъецированных фотосенсибилизатором крысах получены наборы карт действующих сосудов, фотоплетизмограмм и значений плотности сосудов кожи до, во время и после фотоактивации в двух режимах генерации. Проведен совместный анализ данных видеокапилляроскопии, фотоплетизмографии и лазерной доплеровской флоуметрии. Показано, что предложенный подход позволяет выявить различия в механизмах реакции микроциркуляции на фотодинамические воздействие с малой плотностью мощности в различных режимах, в частности, несовпадение времени от начала экспозиции до остановки кровотока и начала восстановительного периода.

The proposed approach to microcirculation assessment is non-invasive, informative, and can be implemented during photoactivation, and thus is perspective both for research tasks and clinical practice. The functional principles of the vasculature response to photodynamic exposure, identified using this technique, also foster the efficiency and safety of photodynamic therapy. The developed setup allows simultaneous photodynamic exposure and studying the microcirculation parameters by videocapillaroscopy and photoplethysmography techniques. Photodynamic action is carried out by 662 nm laser radiation with a power density of 15 mW/cm2  in continuous and pulsed modes. The imaging system of the setup consists of a large working distance microscope, an optical filter, and a monochrome camera. The illumination system is based on LED with a central wavelength of 532 nm. The acquired images were processed in order to obtain morphometric and hemodynamic microcirculation data in the inspected skin area. To compare the proposed approach with existing methods, we measured blood flow parameters by a laser Doppler flowmeter. We tested the developed setup on rats injected with a photosensitizer and obtained active vessel maps, photoplethysmograms, and skin vessel density values before, during, and after photoactivation in both generation modes. The proposed approach allows to reveal differences in the microcirculation response to photodynamic effects of low power densities in different modes, in particular, the discrepancy between the time from the start of exposure to the cessation of blood flow and the start of the recovery period.

фотодинамическая терапиямикроциркуляцияфотоплетизмографиявидеокапилляроскопиялазерная допплеровская флоуметрияphotodynamic therapymicrocirculationphotoplethysmographyvideocapillaroscopylaser Doppler flowmetryReferencesDougherty T.J. et al. Photodynamic Therapy JNCI: Journal of the National Cancer Institute // Oxford Academic. – 1998. – Vol. 90(12). – P. 889-905.Dougherty T.J. et al. Photodynamic Therapy JNCI: Journal of the National Cancer Institute. Oxford Academic, 1998. Vol. 90(12), рр. 889-905.Li X. et al. Clinical development and potential of photothermal and photodynamic therapies for cancer // Nature Publishing Group. – 2020. – Vol. 17(11). – P. 657-674.Li X. et al. Clinical development and potential of photothermal and photodynamic therapies for cancer. Nature Publishing Group, 2020, Vol. 17(11), pp. 657-674.Korbelik M. et al. Nitric oxide production by tumour tissue: impact on the response to photodynamic therapy // Br J Cancer. Nature Publishing Group. – 2000. – Vol. 82(11). – P. 1835.Korbelik M. et al. Nitric oxide production by tumour tissue: impact on the response to photodynamic therapy. Br J Cancer. Nature Publishing Group, 2000, Vol. 82(11), p. 1835.Souza C.S. et al. Long-term follow-up of topical 5-aminolaevulinic acid photodynamic therapy diode laser single session for nonmelanoma skin cancer // Photodiagnosis Photodyn Ther. – 2009. – Vol. 6 (3-4). – P. 207-213.Souza C.S. et al. Long-term follow-up of topical 5-aminolaevulinic acid photodynamic therapy diode laser single session for nonmelanoma skin cancer. Photodiagnosis Photodyn Ther, 2009, Vol. 6 (3-4), pp. 207-213.Chen D. et al. Intraoperative monitoring of blood perfusion in port wine stains by laser Doppler imaging during vascular targeted photodynamic therapy: A preliminary study // Photodiagnosis Photodyn Ther. Elsevier. – 2016. – Vol. 14. – P.142-151.Chen D. et al. Intraoperative monitoring of blood perfusion in port wine stains by laser Doppler imaging during vascular targeted photodynamic therapy: A preliminary study. Photodiagnosis Photodyn Ther. Elsevier, 2016, Vol. 14, pp. 142-151.Orlova A. et al. Diffuse Optical Spectroscopy Monitoring of Experimental Tumor Oxygenation after Red and Blue Light Photodynamic Therapy // Multidisciplinary Digital Publishing Institute. – 2021. – Vol. 9(1). – P. 19.Orlova A. et al. Diffuse Optical Spectroscopy Monitoring of Experimental Tumor Oxygenation after Red and Blue Light Photodynamic Therapy. Photonics 2022, Vol. 9, p. 19. Multidisciplinary Digital Publishing Institute, 2021. Vol. 9(1), p. 19.Khurana M. et al. Intravital high-resolution optical imaging of individual vessel response to photodynamic treatment // J Biomed Opt. J Biomed Opt. – 2008. – Vol. 13(4). – P. 1.Khurana M. et al. Intravital high-resolution optical imaging of individual vessel response to photodynamic treatment. J Biomed Opt, 2008, Vol. 13(4), p. 1.Grishacheva T.G. et al. Digital Analysis of Colposcopic Images Before and After Photodynamic Therapy with Open Source Software ImageJ and Fluorescence diagnostics // Optica Publishing Group. – 2020. – P. JW3A.2.Grishacheva T.G. et al. Digital Analysis of Colposcopic Images Before and After Photodynamic Therapy with Open Source Software ImageJ and Fluorescence diagnostics. Optica Publishing Group, 2020, p. JW3A.2.Christou E.E. et al. Evaluation of the choriocapillaris after photodynamic therapy for chronic central serous chorioretinopathy. A review of optical coherence tomography angiography (OCT-A) studies // Graefes Arch Clin Exp Ophthalmol. Graefes Arch Clin Exp Ophthalmol. – 2022. – Vol. 260(6). – P. 1823-1835.Christou E.E. et al. Evaluation of the choriocapillaris after photodynamic therapy for chronic central serous chorioretinopathy. A review of optical coherence tomography angiography (OCT-A) studies. Graefes Arch Clin Exp Ophthalmol. Graefes Arch Clin Exp Ophthalmol, 2022, Vol. 260(6), pp. 1823-1835.Gallucci F. et al. Indications and results of videocapillaroscopy in clinical practice // Advances in medical sciences. – 2008. – Vol. 53(2). – P. 149-157.Gallucci F. et al. Indications and results of videocapillaroscopy in clinical practice. Advances in medical sciences, 2008, Vol. 53(2), pp. 149-157.Machikhin A.S. et al. Exoscope-based videocapillaroscopy system for in vivo skin microcirculation imaging of various body areas. Optica Publishing Group. – 2021. – Vol. 12(8). – P. 4627-4636.Machikhin A.S. et al. Exoscope-based videocapillaroscopy system for in vivo skin microcirculation imaging of various body areas. Biomedical Optics Express, 2021, Vol. 12(8), pp. 4627-4636. Optica Publishing Group, 2021, Vol. 12(8), pp. 4627-4636.Da Silva F.A.M., Newman E.L. Dynamic capillaroscopy: a minimally invasive technique for assessing photodynamic effectS in vivo // Photochem Photobiol. John Wiley & Sons, Ltd. – 1993. – P. Vol. 58(6). – P. 884-889.Da Silva F.A.M., Newman E.L. Dynamic capillaroscopy: a minimally invasive technique for assessing photodynamic effectS in vivo. Photochem Photobiol. John Wiley & Sons, Ltd, 1993, Vol. 58(6), pp. 884-889.Kamshilin A.A. et al. A new look at the essence of the imaging photoplethysmography. Scientific Reports. Nature Publishing Group. – 2015. – Vol. 5(1). – P. 1-9.Kamshilin A.A. et al. A new look at the essence of the imaging photoplethysmography. Scientific Reports. Nature Publishing Group, 2015. Vol. 5(1), pp. 1-9.Kumar M. et al. PulseCam: a camera-based, motion-robust and highly sensitive blood perfusion imaging modality // Nature Publishing Group. – 2020. – Vol. 10(1). – P. 1-17.Kumar M. et al. PulseCam: a camera-based, motion-robust and highly sensitive blood perfusion imaging modality. Scientific Reports, 2020, Vol. 10(1), Nature Publishing Group, 2020. Vol. 10(1), pp. 1-17.Park J. et al. Photoplethysmogram Analysis and Applications: An Integrative Review // Front Physiol. Frontiers Media S.A. – 2022. – Vol. 12. – P. 2511.Park J. et al. Photoplethysmogram Analysis and Applications: An Integrative Review. Front Physiol. Frontiers Media S.A., 2022, Vol. 12, p. 2511.Allen J. Photoplethysmography and its application in clinical physiological measurement // Physiol Meas. Physiol Meas. – 2007. – Vol. 28(3). – С. R1Allen J. Photoplethysmography and its application in clinical physiological measurement. Physiol Meas, 2007. Vol. 28(3).Guryleva A.V. et al. Feasibility of videocapillaroscopy for characterization of microvascular patterns in skin lesions // Proceedings of SPIE – The International Society for Optical Engineering. – 2022. – Vol. 12147.Guryleva A.V. et al. Feasibility of videocapillaroscopy for characterization of microvascular patterns in skin lesions. Proceedings of SPIE – The International Society for Optical Engineering, 2022, Vol. 12147.Dolmans D.E.J.G.J., Fukumura D., Jain R.K. Photodynamic therapy for cancer // Nature Publishing Group. – 2003. – Vol. 3(5). – P. 380-387.Dolmans D.E.J.G.J., Fukumura D., Jain R.K. Photodynamic therapy for cancer. Nature Reviews Cancer, 2003, Vol. 3(5). Nature Publishing Group, 2003, Vol. 3(5), pp. 380-387.Gunaydin G., Gedik M.E., Ayan S. Photodynamic Therapy—Current Limitations and Novel Approaches // Front Chem. Frontiers Media S.A. – 2021. – Vol. 9. – P. 400.Gunaydin G., Gedik M.E., Ayan S. Photodynamic Therapy—Current Limitations and Novel Approaches. Front Chem. Frontiers Media S.A., 2021. Vol. 9. P. 400.Foster T., et al. Oxygen consumption and diffusion effects in photodynamic therapy // Radiat. Res. – 1991. – Vol. 126. – P. 296-303.Foster T., et al. Oxygen consumption and diffusion effects in photodynamic therapy. Radiat. Res, 1991, Vol. 126, pp. 296-303.Henderson B., et al. Oseroff, Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate // Cancer Res. – 2000. – Vol. 60. – P. 525-529.Henderson B., et al. Oseroff, Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate. Cancer Res, 2000, Vol. 60, pp. 525-529.Klimenko V.V., et al. Pulse mode of laser photodynamic treatment induced cell apoptosis // Photodiagnosis Photodyn Ther. – 2016. – Vol. 13. – P. 101-107.Klimenko V.V., et al. Pulse mode of laser photodynamic treatment induced cell apoptosis. Photodiagnosis Photodyn Ther, 2016, Vol. 13, pp. 101-107.Wilson B.C., Patterson M.S. The physics, biophysics and technology of photodynamic therapy // Phys Med Biol. – 2008. – Vol. 53(9). – P. 61-109.Wilson B.C., Patterson M.S. The physics, biophysics and technology of photodynamic therapy. Phys Med Biol, 2008, Vol. 53(9), pp. 61-109.Abbot N.C. et al. Laser Doppler Perfusion Imaging of Skin Blood Flow Using Red and Near-Infrared Sources // Journal of Investigative Dermatology Elsevier. – 1996. – Vol. 107(6). – P. 882-886.Abbot N.C. et al. Laser Doppler Perfusion Imaging of Skin Blood Flow Using Red and Near-Infrared Sources. Journal of Investigative Dermatology Elsevier, 1996, Vol. 107(6), pp. 882-886.Moço A., Verkruysse W. Pulse oximetry based on photoplethysmography imaging with red and green light: Calibratability and challenges. J Clin Monit Comput // Springer Science and Business Media B.V. – 2021. – Vol. 35(1). – P. 123-133.Moço A., Verkruysse W. Pulse oximetry based on photoplethysmography imaging with red and green light: Calibratability and challenges. J Clin Monit Comput. Springer Science and Business Media B.V., 2021, Vol. 35(1), pp. 123-133.Han S. et al. Design of Multi-Wavelength Optical Sensor Module for Depth-Dependent Photoplethysmography // Multidisciplinary Digital Publishing Institute. – 2019. – Vol. 19(24). – P. 5441.Han S. et al. Design of Multi-Wavelength Optical Sensor Module for Depth-Dependent Photoplethysmography. Multidisciplinary Digital Publishing Institute, 2019. Vol. 19(24), p. 5441.Volkov M. V et al. Evaluation of blood microcirculation parameters by combined use of laser // Doppler flowmetry and videocapillaroscopy methods. – 2017.Volkov M. V et al. Evaluation of blood microcirculation parameters by combined use of laser. Doppler flowmetry and videocapillaroscopy methods, 2017.Dremin V. et al. Dynamic evaluation of blood flow microcirculation by combined use of the laser Doppler flowmetry and high‐speed videocapillaroscopy methods //Journal of biophotonics. – 2019. – Т. 12. – №. 6. – С. e201800317.Dremin V. et al. Dynamic evaluation of blood flow microcirculation by combined use of the laser Doppler flowmetry and highspeed videocapillaroscopy methods. J Biophotonics, 2019, Vol. 12(6).

The authors declare that there are no conflicts of interest present.