This short review reflects the latest achievements of technical science for medicine in the field of creating phototherapeutic technologies for oncology. The article discuss the problem of further developing and applying matrix phototherapeutic apparatus. The comparison and the features of alternative sources based on light emitted diodes structures are considered. The application of photomatrix system for photodynamic therapy and for postmastectomy oedema treatment are presented.
KEYWORDS: In vivo imaging, High speed imaging, Blood, Blood circulation, Biomedical optics, Animal model studies, In vitro testing, Optical resolution, Light scattering, Absorption
In vivo, label-free, high-speed (up to 10,000 with the potential for 40,000 frames per second), high-resolution (up to 300 nm) real-time continuous imaging with successive framing of circulating individual erythrocytes, leukocytes, and platelets in fast blood flow is developed. This technique, used in an animal model, reveals the extremely high dynamic deformability of erythrocytes in natural flow. Potential applications of this technique are discussed with focus on time-resolved monitoring of the cell deformation dynamics in the native biological environment, which may have diagnostic value for the early diagnosis of diseases.
Recently we discovered that in developed integrated flow cytometry using combination high resolution transmission and two beam (pump-probe) of photothermal microscopy with flow module the temporal fluctuation of probe beam even without pump laser pulse are very sensitive to functional states of single cells (e.g. with 2-3 differences in average fluctuation amplitude for live and dead cells). In this paper we are focusing on theoretical and experimental studies of these new phenomena using thermolens schematics with highly stabilized continuous-wave He-Ne laser and photodiode/photomultiplier with pinhole. This scheme allows to study both random and laser-induced thermolens effects in passive and active mode including short and long term monitoring of scattered light fluctuation in trans-illumination mode at single cellular and even sub-cellular levels in vitro, and in vivo. We demonstrate these schematics has some potential to monitor intracellular dynamics including change in cell metabolism, and necrosis, especially, under pump laser impacts in vitro in stationary condition. Besides, we present some relevant data obtained with other similar schematics, including evaluation of bacterial motility by dynamic light scattering. We discuss further potential developing this approach for flow cytometry with fast speed photodetector and digital camera and the multi- wavelength statistical and correlation analysis of speckle-related signals in applications to analysis of complex motions and functional properties of cells in bioflows including the evaluation of the rotational and translational components of the motion of individual live and dead cells.
One of the important problems of modern medicine is treatment of infected wounds. There are many diversified expedients of treatment, but none of them obey the modern physician completely. The aim of this study is to develop and test a new combined method of photodynamic ultrasonic therapy (PDUST) for treatment of infected wounds with focus on experimental trials. PDUST is based on a combination of two methods: photodynamic (PD) therapy (PDT) with photosensitizer and low frequency ultrasonic (US) therapy with antibiotic as tools for treatment of wounds and effectively killing bacteria. The main parameters are: US frequency - 26.5 kHz; US tip elongation - 40±20 μm; wavelength of light emitting diodes (LED) array - 660±10 nm; light intensity on biotissue surface - 1-2 mW/cm2; photosensitizer - an aluminum disulfonated phtalocyanine dissolved in a physiological solution in concentration 10 mg/l. The experiments were carried out with 70 male chinchilla rabbits divided into 7 groups, thus the dynamics of wounds healing were studied in different modes of PDUST. The PD and US methods supplement each other and in conjunction provide additive and especially synergetic effects. The experimental data demonstrated advantages of new technology in comparison with conventional methods in cases of treatment of extended suppurative inflammatory and profound wounds. The more detailed study of PDUST method's mechanism, which is based on low intensity of LED light, PD therapy and US influence is required.
One of the important problems of modern medicine is treatment of urogenital diseases.1-2 There is a set of the treatment methods for such problems, but any of them does not obey the modern physicians completely.3-4 Our aim is to present the new combined therapeutic apparatus called "Yarovit" (produced in Russia, in collaboration between Bauman Moscow State University of Technology and Scientific Production Association and Medical Center "Yarovit") which successfully applied in clinics for cure the patients with copulative dysfunction diseases.5-6 At this apparatus "Yarovit" (description model have abbreviation AMVL-0 1) there is a combination of vacuum decompression (0.1-0.4 kgs/cm2) and light emitting diodes matrix system (660 nm, 1-3 mW/cm2). In treatment procedure apparatus can be applied together with expanded module "Intratherm" (39 °C on average), which has rectal heating elements. The latest clinical studies were made together with volunteer participation of more then one hundred patients, and received results showed the good dynamic of healing. That let to conclude these combinations of physical therapeutic methods supplement each other and in conjunction provides a significant clinical effect. The further developments of such apparatuses are discussed.
Vladimir Zharov, Konstantin Kalinin, Yulian Menyaev, Gregory Zmievskoy, Alexei Savin, Igor Stulin, Raphiz Shihkerimov, Alla Shapkina, Leonid Velsher, Mikhail Stakhanov
The further development of new method of phototherapy based on use of light-emitting diodes (LED) arrays has been presented. LEDs array distribution is side of cylindrical surface, covering pathology region, was used for treatment group of patients with an affected peripheral nervous system. The main group consisted of patients with humeral plexopathy - one of possible neurological manifestation of postmastectomic syndrome as result of breast cancer radical treatment. This disease was accompanied also by some other peripheral nervous system diseases: diabetic polyneuropathy, compression ischemic mononeuropathy, festering wounds and others. The phototherapeutic method is just directed on improvement of patient's conditions in combination with other traditional methods of treatment. The main parameters of photomatrix therapeutic system: wavelength - 660 nm, line width - no more than 20 nm, intensity of radiation on the surface of edema - 0.5-3 mW/cm2 (in dependence of apparatuses type). To control and study efficiency of phototreatment ultrasonic dopplerography, thermography, electromyography and viscosimetry have been used.
Vladimir Zharov, Yulian Menyaev, Konstantin Kalinin, Gregory Zmievskoy, Leonid Velsher, Alexander Podkolzin, Mikhail Stakhanov, Yury Gorchak, V. Sarantsev
A new combined photoultrasonic (CPUS) technology for the treatment of infected wounds is suggested. The CPUS principal operation is based on the topical application of a photosensitizer followed by light irradiation in combination with low frequency ultrasonic (US) treatment of wounds. In CPUS, two methods - photodynamic (PDT) and ultrasonic therapies supplement each other beneficially and in conjunction provide a significant effect of deep suppurative inflammatory wounds treatment. The main advantages of the new technology are the combined application of an antibiotic solution and photodynamic therapy to destroy antibiotic- resistant microorganisms, an effective mixing of a photosensitizer in the wound, the US enhancement of photosensitizer impregnation into the membranes of bacteria, the US clearing of wound surface from necrotic products, an increased effective light dose exposure in the whole volume of the deep wound when the light does not penetrate totally inside the wound, an additional bactericidal effect under the US impact, and the combined effect of CPUS activation of the immune system.
This article presents the further developments of combined laser-ultrasound medical technologies with paying attention the possibility ultrasound in surgery and therapy. The analyses of main effects at the low frequency ultrasonic treatment of biotissues including cavitation, acoustic streams, acoustic pressure, mechanical influence etc are analyzed. The main promising areas of application of low frequency ultrasound are considered including bactericidal treatment of infections wounds, spray treatment of wounds in head and neck surgery, tumor treatment etc. In particular the clinical result of using ultrasonic devices based on imposing ultrasonic oscillations in a range of 22-66 kHz on a cutting instrument with a special form, radiation intensity up to 10 W/cm2 and oscillation amplitude up to 40-60 micrometers with respect to oncology for halt bleeding from a tumor, liquidating pain, acoustic denervation are presented. Some limitation of medical application of ultrasound are discussed and perspective combination with laser for increasing efficiency of new combined technologies are found. Among them: combination photodynamic therapy and ultrasonic treatment of tumors, laser-ultrasonic treatment of infections wounds including using spray, laser-ultrasonic drug delivery. The preliminary result of experimental study of some of above-mentioned technologies are presented.
Standard sources of radiation have not sufficient efficiency at treating spatially extended pathology, especially when pathologic areas involve opposite sides of the human being's body or when they are uneven in shape. The typical examples of such pathology are extensive burns, oedema, inflammatory processes, infectious wounds, actinic keratosis, psoriasis, arthritis and neurological diseases. Superbright LEDs gathered in a matrix and grasping the area of irradiation are the most suitable sources of radiation. This article presents the result of investigation of the effectiveness of various types of the blue-to-infrared spectrum range LED array that allow irradiating a surface with an area from several cm2 to several thousand cm2 including the whole human being's body with the intensity varying from 1 to 100 mW/cm2. Besides the matrixes, composed of separate light diodes, modular systems with separate monolithic hybrid chips with a high density of positioning the sources of radiation are considered. The peculiarities and results of applying such systems to treat oedema, cancer, weight regulation, neurological diseases, different infections diseases in combination with PDT, stomatitis and paradontosis are analyzed. The parameters of the photomatrix LED for different spectral regions and different geometry from flat shape to semispherical and cylindrical are presented. The perspective combination photomatrix LED with another therapeutical devices including photovacuum and photomagnetic therapy are considered.
In photomedicine in some of cases radiation delivery to local zones through optical fibers can be changed for the direct placing of tiny optical sources like semiconductor microlasers or light diodes in required zones of ears, nostrils, larynx, nasopharynx cochlea or alimentary tract. Our study accentuates the creation of optoelectronic microdevices for local phototherapy and functional imaging by using reflected light. Phototherapeutic micromodule consist of the light source, microprocessor and miniature optics with different kind of power supply: from autonomous with built-in batteries to remote supply by using pulsed magnetic field and supersmall coils. The developed prototype photomodule has size (phi) 8X16 mm and work duration with built-in battery and light diode up several hours at the average power from several tenths of mW to few mW. Preliminary clinical tests developed physiotherapeutic micrimodules in stomatology for treating the inflammation and in otolaryngology for treating tonsillitis and otitis are presented. The developed implanted electro- optical sources with typical size (phi) 4X0,8 mm and with remote supply were used for optical stimulation of photosensitive retina structure and electrostimulation of visual nerve. In this scheme the superminiature coil with 30 electrical integrated levels was used. Such devices were implanted in eyes of 175 patients with different vision problems during clinical trials in Institute of Eye's Surgery in Moscow. For functional imaging of skin layered structure LED arrays coupled photodiodes arrays were developed. The possibilities of this device for study drug diffusion and visualization small veins are discussed.
Vladimir Zharov, Yulian Menyaev, Konstantin Kalinin, Andrei Borisov, Alexei Latyshev, Mikhail Stakhanov, Leonid Velsher, Margarita Zhitkova, Victor Sokolov, D. Sukhin, V. Sarantsev
This review reflect the latest achievements of Russian science in the field of creating laser and phototherapeutic combined technologies for oncology. This article tackles the problem of further developing laser-ultrasonic medical technologies and its applications in oncology. The comparison and the features of alternative sources for photodynamic therapy including the lasers, the lamps with spectral filters and LED array are considered. The application photomatrix system for treatment posmastectomy oedema are presented. The possibilities of laser transcutaneous photosensitizer delivery methods are discussed.
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