Andrey Dunaev | Orel State University (original) (raw)

articles by Andrey Dunaev

The first steps in systematization and analysis of the most fundamental and specific metrological... more The first steps in systematization and analysis of the most fundamental and specific metrological terms, concepts, and definitions applicable to noninvasive medical spectrophotometry (NMS) are discussed. An operational approach to the metrology for the purpose of creation and development of fully functional metrological support of NMS is suggested. Some key properties and aspects of optical in vivo measurements in NMS are discussed. Fabrication of simulation measures and introduction to NMS theory and practice of the notion of diagnostic volume of biological tissues are established as well. © 2010 Springer Science+Business Media, Inc.

A scientific approach to the formulation of medical and technical requirements (MTRs) for noninva... more A scientific approach to the formulation of medical and technical requirements (MTRs) for noninvasive spectrophotometric diagnostic devices using optical technologies such as laser Doppler flowmetry and absorption spectroscopy is proposed. The theoretical modeling framework, metrological certification, and testing of these devices are still in the early stages of development. The theoretical estimation of the received signal levels for wavelengths between 514 and 940 nm is highly dependent on the blood volume level in the subject tissue. The proposed approach allows, in particular, the calculation of technical and metrological performance constraints of the instruments, such as the ranges of the sensitivity and power-related signal-to-noise ratios for different spectral channels and different biomedical (biochemical and physiological) parameters. Substantiation of specialized MTRs for the noninvasive spectrophotometric diagnostic devices can enable them to develop to the level of standardized measurement techniques. © 2013 Society of Photo-Optical Instrumentation Engineers.

Multi-functional laser non-invasive diagnostic systems allow the study of a number of microcircul... more Multi-functional laser non-invasive diagnostic systems allow the study of a number of microcirculatory parameters, including index of blood microcirculation (Im) (by laser Doppler flowmetry, LDF) and oxygen saturation (StO2) of skin tissue (by tissue reflectance oximetry, TRO). This research aimed to use such a system to investigate the synchronization of microvascular blood flow and oxygen saturation rhythms under normal and adaptive change conditions. Studies were conducted on eight healthy volunteers of 21-49 years. These volunteers were observed between one and six months, totalling 422 basic tests (3 min each). Measurements were performed on the palmar surface of the right middle finger and the lower forearm's medial surface. Rhythmic oscillations of LDF and TRO were studied using wavelet analysis. Combined tissue oxygen consumption data for all volunteers during 'adaptive changes' increased relative to normal conditions with and without arteriovenous anastomoses. Data analysis revealed resonance and synchronized rhythms in microvascular blood flow and oxygen saturation as an adaptive change in myogenic oscillation (vasomotion) resulting from exercise and possibly psychoemotional stress. Synchronization of myogenic rhythms during adaptive changes may lead to increased oxygen consumption as a result of increased microvascular blood flow velocity. © 2014 Institute of Physics and Engineering in Medicine.

Background and objective: The formation of reactive oxygen species (ROS) is associated with cardi... more Background and objective: The formation of reactive oxygen species (ROS) is associated with cardiovascular disease (CVD). High dietary cholesterol can significantly alter the delicate balance between pro-oxidation and antioxidant defences leading to reactive oxygen species formation in the vasculature, without significant structural changes in tissue composition. We aimed to establish a methodology for the noninvasive assessment of skin fluorescent biomarkers in mice. Materials and methods: C57/black/6 wild-type (WT; n = 25) male mice were subdivided to receive normal rodent chow (n = 11) or a high cholesterol diet (2% cholesterol; n = 14) for 20 weeks. Skin autofluorescence measurements were made on the backs of anaesthetized (1.5-2% isoflurane in oxygen) mice. A laser probe was used to make simultaneous measurements of: collagen, elastin, nicotinamide pyridoxine, flavins, lipofuscin and β-carotene. Results are expressed as group mean in arbitrary units (AU) ± standard error (SE). Hearts were excised and weighed (mg); cardiac hypertrophy was measured by ratio [heart weight (mg)/bodyweight (g) ± SE]. Student's t-test was used for statistical significance analysis (p ≤ 0.05). Results: There were no significant differences between cholesterol- and chow-fed animals for collagen (34 ± 5AU vs. chow 34 ± 4 AU, p = 0.51) and elastin (66 ± 6 AU vs. chow 82 ± 7 AU, p = 0.11). Significant differences were evident for nicotinamide adenine dinucleotide (92 ± 7 AU vs. chow 118 ± 7 AU, p = 0.01), pyridoxine (56 ± 4 AU vs. chow 73 ± 4 AU, p = 0.01), flavins (44 ± 3 AU vs. chow 57 ± 4 AU, p = 0.01), lipofuscin (35 ± 3 AU vs. chow 46 ± 3 AU, p = 0.01) and β-carotene (19 ± 2 AU vs. chow 25 ± 2 AU, p = 0.01). Cholesterol-fed animals had significantly heavier hearts (7 ± 0.3 ratio vs. chow 5 ± 0.1 ratio, p = 0.001). Conclusion: Cholesterol feeding induced cardiovascular disease as noted by cardiac hypertrophy in wild-type mice. A reduction was observed in pyridoxine, nicotinamide adenine dinucleotide, flavins, lipofuscin and β-carotene, which are established risk factors for cardiovascular disease. We report no significant changes in structural proteins collagen and elastin, suggesting no generalized tissue restructuring, which might otherwise explain the observed pathological differences. © 2014 Royal Microscopical Society.

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The main problems of metrological assurance for laser Doppler flowmetry (LDF) devices that inhibi... more The main problems of metrological assurance for laser Doppler flowmetry (LDF) devices that inhibit the further development of this diagnostic technology are discussed. The proposed method and device for monitoring the metrological status of LDF devices, characterized by the use of the principle of signal playback of Doppler shift based on probing the oscillating light-diffusing Lambertian surface, allow checking the metrological characteristics of LDF devices. © 2014, Springer Science+Business Media New York.

Fluorescence spectroscopy has recently become more common in clinical medicine. However, there ar... more Fluorescence spectroscopy has recently become more common in clinical medicine. However, there are still many unresolved issues related to the methodology and implementation of instruments with this technology. In this study, we aimed to assess individual variability of fluorescence parameters of endogenous markers (NADH, FAD, etc.) measured by fluorescent spectroscopy (FS) in situ and to analyse the factors that lead to a significant scatter of results. Most studied fluorophores have an acceptable scatter of values (mostly up to 30%) for diagnostic purposes. Here we provide evidence that the level of blood volume in tissue impacts FS data with a significant inverse correlation. The distribution function of the fluorescence intensity and the fluorescent contrast coefficient values are a function of the normal distribution for most of the studied fluorophores and the redox ratio. The effects of various physiological (different content of skin melanin) and technical (characteristics of optical filters) factors on the measurement results were additionally studied.The data on the variability of the measurement results in FS should be considered when interpreting the diagnostic parameters, as well as when developing new algorithms for data processing and FS devices. © 2015 IPEM.

The time course of changes in the parameters of microcirculatory–tissue systems (MTSs) during the... more The time course of changes in the parameters of microcirculatory–tissue systems (MTSs) during the cold pressor test (CPT) was investigated in 32 conventionally healthy volunteers by noninvasive optical methods of laser Doppler flowmetry (LDF), tissue reflectance oximetry (TRO), and pulse oximetry. Depending on the oxygen consumption recovery rate in the CPT, the subjects were conventionally divided into two groups, one with a normal physiology and the other with a tendency to vascular spasm and lack of functional recovery of the MTSs. Blood flow oscillations were analyzed in detail to identify the possible causes of vascular spasm. The causes might include a distortion of the tone-shaping myogenic mechanisms that regulate resistive microvessels, blood congestion in microcirculation, or a combination of both of the factors. The CPT used to assess the MTS function was assumed to report the MTS reserve and to detect a propensity for vascular spasm at a preclinical stage, thus being of a potential applied significance. © 2015, Pleiades Publishing, Inc.

Using non-invasive optical methods of laser Doppler flowmetry, tissue reflectance oximetry and pu... more Using non-invasive optical methods of laser Doppler flowmetry, tissue reflectance oximetry and pulse oximetry, we investigated the dynamics of parameter changes of microcirculatory-tissue systems (MTS) when using cold pressor test (CPT) on 32 conventionally healthy volunteers. According to differences in the recovery rate of oxygen consumption during CPT, volunteers can be conditionally divided into 2 groups: 1--displaying normal physiology and 2--with a tendency to angiospasm and lack of functional recovery of the MTS. To identify possible causes of angiospasm, we performed a detailed analysis of blood flow oscillations. This analysis revealed that the cause of angiospasm may be a violation of the tone-shaping myogenic mechanisms regulating resistive microvessels, disturbances to the microcirculation of stagnant blood, or a combination of both of these factors. Use of the CPT for functional assessment of MTS allows us not only to estimate the reserve capabilities of the MTS, but also to identify--at a pre-clinical stage-propensity to angiospasm, which has practical value in the clinic.

The influence of various melanin concentrations on the endogenous fluorescence intensity of biolo... more The influence of various melanin concentrations on the endogenous fluorescence intensity of biological tissue has been experimentally studied, and the fluorescence signals have been modeled by the Monte Carlo method. The modeling is based on a four-layer optical model of the skin, using known optical parameters of skin with various melanin concentrations. The fluorescence spectra obtained by the Monte Carlo method agrees with the results of the experimental investigations. © 2016 Optical Society of America.

Urinary bladder diseases are a common problem throughout the world and often difficult to accurat... more Urinary bladder diseases are a common problem throughout the world and often difficult to accurately diagnose. Furthermore, they pose a heavy financial burden on health services. Urinary bladder tissue from male pigs was spectrophotometrically measured and the resulting data used to calculate the absorption, transmission, and reflectance parameters, along with the derived coefficients of scattering and absorption. These were employed to create a "generic" computational bladder model based on optical properties, simulating the propagation of photons through the tissue at different wavelengths. Using the Monte-Carlo method and fluorescence spectra of UV and blue excited wavelength, diagnostically important biomarkers were modeled. Additionally, the multifunctional noninvasive diagnostics system "LAKK-M" was used to gather fluorescence data to further provide essential comparisons. The ultimate goal of the study was to successfully simulate the effects of varying excited radiation wavelengths on bladder tissue to determine the effectiveness of photonics diagnostic devices. With increased accuracy, this model could be used to reliably aid in differentiating healthy and pathological tissues within the bladder and potentially other hollow organs. © 2016 Society of Photo-Optical Instrumentation Engineers (SPIE).

Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the... more Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients. © 2016 Optical Society of America.

Immunoinflammatory reactions affecting the state of the microvasculature play the key role in the... more Immunoinflammatory reactions affecting the state of the microvasculature play the key role in the genesis of rheumatic diseases. Therefore, it is important to develop new methods for the early detection of microcirculatory disorders. The purpose of this study was to assess the possibilities of diffuse reflectance spectroscopy used to identify microcirculatory disturbances in patients with rheumatic diseases by measuring skin blood supply and oxygenation rate and their relationship with the varying degrees of inflammatory activity. A total of 36 patients with rheumatic diseases and 31 healthy volunteers took part in the study. We analyzed the skin diffuse reflectance spectra recorded on the palmar side of the distal phalange of the right middle finger using a FLAME spectrometer. The erythema index and saturation rate were calculated to quantify the content of hemoglobin and oxygen saturation of tissues in both groups. The differences in the parameters under study between the groups were found to be statistically significant. The average value of erythema index was twofold higher in patients with rheumatic diseases with the second degree of inflammatory activity and about 2.5-fold higher in patients with the third degree of inflammatory activity, compared to the control group. This fact indicates impaired blood circulation with increased blood flow caused by inflammatory processes. Thus, diffuse reflectance spectroscopy can be used as an additional non-invasive diagnostic test for assessing the severity of microcirculatory disturbances and the activity of inflammation in rheumatic diseases. © 2017, Pleiades Publishing, Inc.

We introduce a noninvasive diagnostic approach for functional monitoring of blood microflows in c... more We introduce a noninvasive diagnostic approach for functional monitoring of blood microflows in capillaries and thermoregulatory vessels within the skin. The measuring system is based on the combined use of laser Doppler flowmetry and skin contact thermometry. The obtained results suggest that monitoring of blood microcirculation during the occlusion, performed in conjunction with the skin temperature measurements in the thermally stabilized medium, has a great potential for quantitative assessment of angiospatic dysfunctions of the peripheral blood vessels. The indices of blood flow reserve and temperature response were measured and used as the primarily parameters of the functional diagnostics of the peripheral vessels of skin. Utilizing these parameters, a simple phenomenological model has been suggested to identify patients with angiospastic violations in the vascular system. © 2017 Society of Photo-Optical Instrumentation Engineers (SPIE).

The article suggests a method and a device for diagnostics of the functional state of peripheral ... more The article suggests a method and a device for diagnostics of the functional state of peripheral vessels of the upper limbs, which provide identification of angiospastic disorders with a lower probability of false-negative result, allowing thereby the quality of diagnostics to be improved. The suggested approach is based on combined application of laser Doppler flowmetry and contact thermometry during an occlusion test. The obtained results can be used in various fields of medicine for the development of multi-functional non-invasive diagnostic systems for the diagnosis and prevention of diseases associated with changes in the functional state of peripheral vessels. © 2017, Springer Science+Business Media New York.

The use of liposomal nanoparticles with an incorporated active substance is an innovative and pro... more The use of liposomal nanoparticles with an incorporated active substance is an innovative and promising approach to diagnostics and therapy. The application of liposomal nanoparticle-based drugs allows for targeted localized delivery, overcomes the natural barriers within the body effectively, and minimizes possible side effects. Liposomes are able to contain a variety of ingredients with practically no limitations to their chemical composition, chemical properties, or size of constituent molecules. This study evaluated the ability to control the passage of fluorescent dye-filled liposomes through the intestinal mucosal barrier after oral administration. For this purpose, the increase in transcutaneous registered fluorescence from tetrabromofluorescein dye was recorded and analysed. Fluorescence intensity was measured at the proximal end of the tail of an animal model after oral administration of the liposomes. Measurements were taken at the excitation wavelengths of 365 and 450 nm. The fluorescence intensity in the group treated with the fluorescent contrast agent encapsulated in liposomal particles increased 140% of the initial level, but in the group treated with pure contrast agent, the increase in detected fluorescence intensity did not exceed 110%. Mice that received empty liposomes as well as the control group did not demonstrate statistically significant changes in fluorescence intensity. A potential application of our results is an express laser optical method of monitoring the transport of orally administered liposomal particles. The results can be used to help create new optical tools for use in the development of new drugs and in high-throughput screening used during their testing. © 2017 Astro Ltd.

Laser Doppler flowmetry (LDF) has been applied for the assessment of variation in blood microflow... more Laser Doppler flowmetry (LDF) has been applied for the assessment of variation in blood microflows in patients with rheumatic diseases and healthy volunteers. Oscillations of peripheral blood microcirculation observed by LDF have been analyzed utilizing a wavelet transform. A higher amplitude of blood microflow oscillations has been observed in a high frequency band (over 0.1 Hz) in patients with rheumatic diseases. Oscillations in the high frequency band decreased in healthy volunteers in response to the cold pressor test, whereas lower frequency pulsations prevailed in patients with rheumatic diseases. A higher perfusion rate at normal conditions was observed in patients, and a weaker response to cold stimulation was observed in healthy volunteers. Analysis of blood microflow oscillations has a high potential for evaluation of mechanisms of blood flow regulation and diagnosis of vascular abnormalities associated with rheumatic diseases. © 2017 Society of Photo-Optical Instrumentation Engineers (SPIE).

According to the International Diabetes Federation, the challenge of early stage diagnosis and tr... more According to the International Diabetes Federation, the challenge of early stage diagnosis and treatment effectiveness monitoring in diabetes is currently one of the highest priorities in modern healthcare. The potential of combined measurements of skin fluorescence and blood perfusion by the laser Doppler flowmetry method in diagnostics of low limb diabetes complications was evaluated. Using Monte Carlo probabilistic modeling, the diagnostic volume and depth of the diagnosis were evaluated. The experimental study involved 76 patients with type 2 diabetes mellitus. These patients were divided into two groups depending on the degree of complications. The control group consisted of 48 healthy volunteers. The local thermal stimulation was selected as a stimulus on the blood microcirculation system. The experimental studies have shown that diabetic patients have elevated values of normalized fluorescence amplitudes, as well as a lower perfusion response to local heating. In the group of people with diabetes with trophic ulcers, these parameters also significantly differ from the control and diabetes only groups. Thus, the intensity of skin fluorescence and level of tissue blood perfusion can act as markers for various degrees of complications from the beginning of diabetes to the formation of trophic ulcers. © 2017 Society of Photo-Optical Instrumentation Engineers (SPIE).

Bladder cancer is among the most common cancers in the UK and conventional detection techniques s... more Bladder cancer is among the most common cancers in the UK and conventional detection techniques suffer from low sensitivity, low specificity, or both. Recent attempts to address the disparity have led to progress in the field of autofluorescence as a means to diagnose the disease with high efficiency, however there is still a lot not known about autofluorescence profiles in the disease. The multi-functional diagnostic system “LAKK-M” was used to assess autofluorescence profiles of healthy and cancerous bladder tissue to identify novel biomarkers of the disease. Statistically significant differences were observed in the optical redox ratio (a measure of tissue metabolic activity), the amplitude of endogenous porphyrins and the NADH/porphyrin ratio between tissue types. These findings could advance understanding of bladder cancer and aid in the development of new techniques for detection and surveillance. (Figure presented.). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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A method of control of the absorbed dose of radiation during low-level laser therapy is proposed.... more A method of control of the absorbed dose of radiation during low-level laser therapy is proposed. It is based on registration of both the reflected part of energy and part of energy spent on local heating of epidermis. Results of theoretical and experimental studies of heating process at pulse action are presented. As a device controlling the absorbed dose a therapeutic machine is proposed. The intensity of its action can be adjusted depending on optical and thermophysical properties of the biological tissue.

The integration of multiple optical techniques within a single diagnostic device is used to addre... more The integration of multiple optical techniques within a single diagnostic device is used to address the difficulties in standardising measurement of cutaneous blood micro-dynamics caused by high variability. We demonstrate the benefits of simultaneous assessment of blood relative volume (Vb), microcirculation index (Im) and tissue oxygen saturation (S tO2), during long-term examination of healthy volunteers. Consequently, five rhythmic components: endothelial, neurogenic, myogenic, breath and heart pulses were established showing high variability up to 30 - 50% as well as in initial parameters around 16%. All rhythmic components were synchronous with some latency between Im and StO 2 in the myogenic component supports the hypothesis of strong correlation between peripheral hemodynamics and oxygen utilisation in tissues. © 2013 Copyright SPIE.

Fluorescent spectroscopy (FS) is becoming more widely used in chemistry, biology, in various fiel... more Fluorescent spectroscopy (FS) is becoming more widely used in chemistry, biology, in various fields of medical technology and medicine in general. Many purulent wounds, burns and other destructive inflammatory processes are accompanied by changes in the fluorescent activity of the tissues, which occurs due to a misbalance in accumulation of natural fluorophores: FAD, NADH, lipofuscin, porphyrins, structural proteins, etc. The study of redox ratio (RR), characterizing the metabolic processes, is important in the assessment of the metabolic activity ofmicrocirculatory-tissue systems (MTS). However, one of the big problems of the FS method is still the correct interpretation of the data and the development of practical methods for its application in clinical medicine. To solve this problem and create new diagnostic criteria, we propose to evaluate the adaptive capacity of MTS using indicators of links between nutritive blood flow and redox ratio during a physiological rest and functional load (occlusion test). As is known, these parameters (RR and nutritive blood flow) characterize the metabolic activity of tissues.We have performedan experimental study of the relationship between the RR, defined by FS, and nutritive blood flow, defined by the methods of laser Doppler flowmetry. Preliminary results in the study of a complex approach to diagnosis of the state of biological tissue were obtained. A positive relationship between the nutritive blood flow in the microcirculatory channel and RR of skin tissue is observed.The speed of change of metabolism in the phase of occlusion and reperfusion and duration of phase of recovery may be the criteria for adaptive capabilities of MTS, which has practical significance for physiology and medicine. © 2015 SPIE.

Multi-functional laser non-invasive diagnostic systems, such as "LAKK-M", allow the study of a nu... more Multi-functional laser non-invasive diagnostic systems, such as "LAKK-M", allow the study of a number of microcirculatory parameters, including blood microcirculatory index (Im) (by laser Doppler flowmetry, LDF) and oxygen saturation (StO2) of skin tissue (by tissue reflectance oximetry, TRO). Such systems may provide significant information relevant to physiology and clinical medicine. The aim of this research was to use such a system to study the synchronization of microvascular blood flow and oxygen saturation rhythms under normal and adaptive change conditions. Studies were conducted with 8 healthy volunteers - 3 females and 5 males of 21-49 years. Each volunteer was subjected to basic 3 minute tests. The volunteers were observed for between 1-4 months each, totalling 422 basic tests. Measurements were performed on the palmar surface of the right middle finger and the forearm medial surface. Wavelet analysis was used to study rhythmic oscillations in LDF- and TRO-data. Tissue oxygen consumption (from arterial and venal blood oxygen saturation and nutritive flux volume) was calculated for all volunteers during "adaptive changes" as (617±123 AU) and (102±38 AU) with and without arteriovenous anastomoses (AVAs) respectively. This demonstrates increased consumption compared to normal (495±170 AU) and (69±40 AU) with and without AVAs respectively. Data analysis demonstrated the emergence of resonance and synchronization of rhythms of microvascular blood flow and oxygen saturation as an adaptive change in myogenic oscillation (vasomotion) resulting from exercise and potentially from psychoemotional stress. Synchronization of myogenic rhythms during adaptive changes suggest increased oxygen consumption resulting from increased microvascular blood flow velocity.

The metrological basis for optical non-invasive diagnostic devices is an unresolved issue. A majo... more The metrological basis for optical non-invasive diagnostic devices is an unresolved issue. A major challenge for laser Doppler flowmetry (LDF) is the need to compare the outputs from individual devices and various manufacturers to identify variations useful in clinical diagnostics. The most common methods for instrument calibration are simulants or phantoms composed of colloids of light-scattering particles which simulate the motion of red blood cells based on Brownian motion. However, such systems have limited accuracy or stability and cannot calibrate for the known rhythmic components of perfusion (0.0095-1.6 Hz). To solve this problem, we propose the design of a novel technique based on the simulation of moving particles using an electromechanical transducer, in which a precision piezoelectric actuator is used (e.g., P-602.8SL with maximum movement less than 1 mm). In this system, Doppler shift is generated in the layered structure of different solid materials with different optical light diffusing properties. This comprises a fixed, light transparent upper plane-parallel plate and an oscillating fluoroplastic (PTFE) disk. Preliminary studies on this experimental setup using the LDF-channel of a "LAKK-M" system demonstrated the detection of the linear portion (0-10 Hz with a maximum signal corresponding to Doppler shift of about 20 kHz) of the LDF-signal from the oscillating frequency of the moving layer. The results suggest the possibility of applying this technique for the calibration of LDF devices. © 2014 SPIE.

In 1980-2000 besides the laser surgery an intensive evolution of Low Level Laser Therapy (LLLT) h... more In 1980-2000 besides the laser surgery an intensive evolution of Low Level Laser Therapy (LLLT) had started in medicine, especially in Russia as well as in several other East-European countries. At the same time the biophysical mechanisms of LLLT are still the subject of disputes. One of the most popular clinical effects at Low Level Laser Irradiation (LLLI) being mentioned in medical publications for justification of the LLLT healing outcome is a stimulation of blood microcirculation in irradiated area. It was declared a priori at a dawn of LLLT and is now a basis of medical interpretation of healing mechanisms of LLLT at least in Russia. But in past 20 years a lot of investigation was carried out on optical registration of microhaemodynamic parameters in vivo as well as a number of noninvasive diagnostic tools was created for that. So, today it is possible to experimentally check the blood microcirculation stimulation hypothesis. Our study was aimed on that during the past 10 years. The most precision and accurate experiments we have carried out recently using simultaneously three different noninvasive diagnostic techniques: Laser Doppler Flowmetry, Tissue Reflectance Oximetry and Infrared Thermography. All these methods didna't confirm the effect on the blood microcirculation stimulation in skin or mucosa at irradiation with the power density below 50 mW/cm2 and irradiation time up to 5-6 minutes. Above this threshold the heating on 0,8. © 2014 SPIE..1 °C of tissue in the field of irradiation and the corresponding synchronous increase of all parameters of microhemodynamics were observed. © 2014 SPIE.

Diseases of urinary bladder are a common healthcare problem world over. Diagnostic precision and ... more Diseases of urinary bladder are a common healthcare problem world over. Diagnostic precision and predicting response to treatment are major issues. This study aims to create an optical cross-sectionional model of a bladder, capable of visually representing the passage of photons through the tissue layers. The absorption, transmission and reflectance data, along with the derived transmission coefficients (of scattering and absorption) were obtained from literature analysis and were used in the creation of a "generic" cross-section optical property model simulating the passage of thousands of photons through the tissue at different wavelengths. Fluorescence spectra of diagnostically relevant biomarkers excited by the UV and blue wavelengths were modelled on the basis of the Monte-Carlo method. Further to this, fluorescence data gathered by the "LAKK-M" system from pig bladders was applied to the model for a specific representation of the photon passage through the tissues. The ultimate goal of this study is to employ this model to simulate the effects of different laser wavelength and energy inputs to bladder tissue and to determine the effectiveness of potential photonics based devices for the diagnosis of bladder pathologies. The model will aid in observing differences between healthy and pathological bladder tissues registered by photonics based devices.

Skin blood microcirculation and the metabolism activity of tissue were examined on the patients w... more Skin blood microcirculation and the metabolism activity of tissue were examined on the patients with type 2 diabetes. Laser Doppler flowmetry (LDF) with 1064 nm laser light source and fluorescence spectroscopy (FS) with excitation light of 365 nm and 450 nm have been used to monitor the blood perfusion and the content of coenzymes NADH and FAD. Concluding, the proposed combined LDF and tissue FS approach allows to identify the significant violations in the blood microcirculation and metabolic activity for type 2 diabetes patients. © 2016 SPIE.

This study examines the effect of blood absorption on the endogenous fluorescence signal intensit... more This study examines the effect of blood absorption on the endogenous fluorescence signal intensity of biological tissues. Experimental studies were conducted to identify these effects. To register the fluorescence intensity, the fluorescence spectroscopy method was employed. The intensity of the blood flow was measured by laser Doppler flowmetry. We proposed one possible implementation of the Monte Carlo method for the theoretical analysis of the effect of blood on the fluorescence signals. The simulation is constructed as a four-layer skin optical model based on the known optical parameters of the skin with different levels of blood supply. With the help of the simulation, we demonstrate how the level of blood supply can affect the appearance of the fluorescence spectra. In addition, to describe the properties of biological tissue, which may affect the fluorescence spectra, we turned to the method of diffuse reflectance spectroscopy (DRS). Using the spectral data provided by the DRS, the tissue attenuation effect can be extracted and used to correct the fluorescence spectra. © 2016 SPIE.

Vasospastic disorders are a common class of rheumatic disease. These include syndromes such as ve... more Vasospastic disorders are a common class of rheumatic disease. These include syndromes such as vegetative dystonia, Raynaud's syndrome, vibration disease and rheumatoid arthritis among others. The aim of this work is to develop an original method of diagnosing the functional state of peripheral vessels of the fingers, based on the simultaneous recording of LDF- and thermograms during the occlusion test, for determining vascular disorders of rheumatological patients. A diagnostic method was developed for assessing the functional state of the peripheral vessels of fingers, based on carrying out occlusion test in a thermally stabilized environment, with simultaneous recording of signals of laser Doppler flowmetry and skin thermometry. To verify the diagnostic value of the proposed method, a series of experiments were carried out on 41 rheumatological patients: 5 male and 36 females (average age 56.0±12.2 years). The most common diagnoses in the patient group were rheumatoid arthritis, arthrosis, gout and systemic lupus erythematosus. The laser analyser of blood microcirculation "LAKK-02" (SPE "LAZMA" Ltd, Russia) and a custom developed multi-channel thermometry device for low inertia thermometry were used for experimental measurements. The measurements of cutaneous temperature and the index of microcirculation were performed on the distal phalanx of the third finger of the right hand. Occlusion tests were performed with water baths at 25 and 42 °C and a tonometer cuff with a pressure of 200-220 mmHg for 3 min on the upper arm. The results of experimental studies are presented and interpreted. These data indicate a violation of the blood supply regulation in the form of a pronounced tendency towards microvascular vasoconstriction in the fingers. Thus, the response displaying a tendency toward angiospasm among patients in the rheumatological diseases profile group was observed mainly in the most severe cases (49 % of this group). The prospects of the developed diagnostic method of microcirculatory disorders in rheumatic diseases are evaluated. Thus, cutaneous blood microcirculation and temperature measurements performed together can help in diagnosis of the functional state of peripheral vessels both in a healthy state and when expressing pathology. © 2016 SPIE.

The aim of this work was to study the possibilities of the laser Doppler flowmetry method for the... more The aim of this work was to study the possibilities of the laser Doppler flowmetry method for the joint study of microhaemo- and lymph circulation of human skin. Conducting a series of experimental studies allowed to trace the relationship of recorded signals of microcirculation of blood flow and lymph flow, as well as to study their oscillation nature by using wavelet analysis. © 2017 SPIE.

The studies were carried out on groups of clinically healthy mice line of outbred CD-1 stock. The... more The studies were carried out on groups of clinically healthy mice line of outbred CD-1 stock. The model animals were divided into 2 groups and received experimental liposomal formulations. Using the method of fluorescence spectroscopy, we investigated the effectiveness of penetration into the circulatory system of fluorescently stained liposomes with polyethylene glycol (PEG) and without PEG when administered orally. Fluorescence channel with a fiber probe series of multifunctional laser non-invasive diagnostic system "LAKK-M" (SPE "LAZMA" Ltd, Russia) was used as the measuring equipment. © COPYRIGHT SPIE.

Laser Doppler flowmetry (LDF) is widely used for diagnosing blood microcirculation diseases. It i... more Laser Doppler flowmetry (LDF) is widely used for diagnosing blood microcirculation diseases. It is well known that the Doppler shift of laser radiation scattered by moving red blood cells (RBC) can be assessed through analyzing photocurrent produced by a photodetector. LDF signal contains information about regulating blood flow rhythms: myogenic, cardiac, nervous and endothelial. The method of videocapillaroscopy (VCS) allows local capillary blood flow velocity evaluation and, using video data processing algorithms, is able to assess RBC velocity changes into capillary. We present the results of simultaneous investigations of changes in tissue perfusion of the distal phalanx of human finger by the LDF as well as changes in capillary blood flow velocity in the nail bed evaluated by the VCS method during arterial occlusion test. The experimental results confirmed the correspondence between blood perfusion and blood flow velocity. © COPYRIGHT SPIE.

This article presents the results of the study of the pressure applied on optical diagnostic prob... more This article presents the results of the study of the pressure applied on optical diagnostic probes as a significant factor affecting the results of measurements. During stepwise increasing and decreasing of local pressure on skin we conducted measurements using the methods of laser Doppler flowmetry and fluorescence spectroscopy. It was found out that pressure on optical probe has sufficient impact on skin microcirculation to affect registered fluorescence intensity. Data obtained in this study are of interest for design and development of diagnostic technologies for wearable devices. This data will also inform further investigation into issues of compensation of blood absorption influence on fluorescence spectrum, allowing increased accuracy and reproducibility of measurements by fluorescence spectroscopy methods in optical diagnosis. © COPYRIGHT SPIE.

An optical instrument for nailfold fluorescence capillaroscopy and image registration has been de... more An optical instrument for nailfold fluorescence capillaroscopy and image registration has been developed. With this instrument, an effect of increasing fluorescence intensity in the spectral range of NADH fluorescence during ischemia was detected. © 2017 SPIE-OSA.

The paper shows the possibility of assessing the functional state of microcirculatory-tissue syst... more The paper shows the possibility of assessing the functional state of microcirculatory-tissue systems of patients with diabetes mellitus by laser Doppler flowmetry (LDF), diffuse reflectance spectroscopy (DRS) and fluorescence spectroscopy (FS) methods. A review of the existing non-invasive optical technologies used to assess the state of microcirculation and oxygen metabolism in tissues of patients with diabetes is conducted. A series of experimental studies involving 76 patients with diabetes and 46 healthy volunteers was carried out. A wavelet analysis of LDF-grams was used to evaluate the adaptive changes of microcirculation during the temperature tests. The obtained data revealed that the proposed methodology in the form of combined use of several diagnostic technologies (LDF, FS and DRS) allows us to detect the presence or absence of trophic disorders and to evaluate adaptation processes during thermal tests. © Published under licence by IOP Publishing Ltd.

Laser Doppler flowmetry (LDF) is a method widely used in diagnosis of microcirculation diseases. ... more Laser Doppler flowmetry (LDF) is a method widely used in diagnosis of microcirculation diseases. It is well known that information about frequency distribution of Doppler spectrum of the laser radiation scattered by moving red blood cells (RBC) usually disappears after signal processing procedure. Photocurrent's spectrum distribution contains valuable diagnostic information about velocity distribution of the RBC. In this research it is proposed to compute the indexes of microcirculation in the sub-ranges of the Doppler spectrum as well as investigate the frequency distribution of the computed indexes. © Published under licence by IOP Publishing Ltd.

This studiy was carried out on groups of clinically healthy male Wistar rats. Animals received di... more This studiy was carried out on groups of clinically healthy male Wistar rats. Animals received distilled drinking water ad libitum for 1 month, water containing succinic acid, water containing zinc sulphate and succinate zinc. Using the method of fluorescence spectroscopy, the parameters of brain metabolism in vivo in a model of laboratory rats was investigated. Based on data obtained by fluorescence spectroscopy, we have registered a change in the degree of cellular respiration in different structures of the cerebral cortex with the toxic effect of zinc compounds and succinic acid on the oxygen exchange process. © 2018 SPIE.

Local hemodynamic parameters were studied by means of laser Doppler flowmetry in 15 patients with... more Local hemodynamic parameters were studied by means of laser Doppler flowmetry in 15 patients with psoriasis in the stationary stage, who have plaques on the inner surface of the forearm. LDF signals recorded at the site of psoriatic lesions of the tissue as well as in the intact tissue at a distance of 1-2 cm from the affected area were analysed. LDF signals were postprocessed by continuous wavelet transform using the Morlet wavelet. © 2018 SPIE.

Diagnostics

Light-based technologies provide unique opportunities for the diagnosis of various pathological d... more Light-based technologies provide unique opportunities for the diagnosis of various pathological disorders of biological tissues [...]

Life

Aggregation of the misfolded proteins β-amyloid, tau, huntingtin, and α-synuclein is one of the m... more Aggregation of the misfolded proteins β-amyloid, tau, huntingtin, and α-synuclein is one of the most important steps in the pathology underlying a wide spectrum of neurodegenerative disorders, including the two most common ones—Alzheimer’s and Parkinson’s disease. Activity and toxicity of these proteins depends on the stage and form of aggregates. Excessive production of free radicals, including reactive oxygen species which lead to oxidative stress, is proven to be involved in the mechanism of pathology in most of neurodegenerative disorders. Both reactive oxygen species and misfolded proteins play a physiological role in the brain, and only deregulation in redox state and aggregation of the proteins leads to pathology. Here, we review the role of misfolded proteins in the activation of ROS production from various sources in neurons and glia. We discuss if free radicals can influence structural changes of the key toxic intermediates and describe the putative mechanisms by which oxi...

Scientific Reports

This paper presents the results of the experiments which were performed using the optical biopsy ... more This paper presents the results of the experiments which were performed using the optical biopsy system specially developed for in vivo tissue classification during the percutaneous needle biopsy (pnB) of the liver. the proposed system includes an optical probe of small diameter acceptable for use in the pnB of the liver. the results of the feasibility studies and actual tests on laboratory mice with inoculated hepatocellular carcinoma and in clinical conditions on patients with liver tumors are presented and discussed. Monte Carlo simulations were carried out to assess the diagnostic volume and to trace the sensing depth. Fluorescence and diffuse reflectance spectroscopy measurements were used to monitor metabolic and morphological changes in tissues. The tissue oxygen saturation was evaluated using a recently developed approach to neural network fitting of diffuse reflectance spectra. The Support Vector Machine Classification was applied to identify intact liver and tumor tissues. Analysis of the obtained results shows the high sensitivity and specificity of the proposed multimodal method. This approach allows to obtain information before the tissue sample is taken, which makes it possible to significantly reduce the number of false-negative biopsies.

Liver cancer remains one of the most widespread cancer types worldwide. The time spent on the dia... more Liver cancer remains one of the most widespread cancer types worldwide. The time spent on the diagnosis is one of crucial factors ensuring the effectiveness of treatment. As percutaneous needle biopsy remains the gold standard for liver diagnosis, it is necessary to develop new methods for improving this procedure. One of the most promising directions is multimodal optical biopsy. The proposed protocol describes the methodology of real-time in vivo optical measurements of liver lesions during the percutaneous needle biopsy of the liver. The multimodal approach combines the methods of fluorescence and diffuse reflectance spectroscopy and conventional histological analysis.

Applied Sciences

The paper presents the results of experimental measurements of endogenous fluorescence and blood ... more The paper presents the results of experimental measurements of endogenous fluorescence and blood perfusion in patients with pathology of the organs of hepatopancreatoduodenal area in vivo. A custom setup combining channels for fluorescence spectroscopy (excitation wavelengths of 365 nm and 450 nm) and laser Doppler flowmetry (1064 nm) with fibre optical probe for nondestructive laparoscopic measurements has been developed and applied during minimally invasive operation procedure. Preliminary measurements with two aforementioned channels have been performed at specified excitation wavelengths. The possibility of obtaining fluorescence spectra and laser Doppler flowmetry signals in vivo during minimally invasive interventions was shown. Obtained data show perspectives of further research on technical and methodological development of optical diagnostic methods for minimally invasive surgery. The obtained results can be used to provide a deeper understanding of pathological processes i...

Journal of Biomedical Photonics & Engineering

Optical techniques are one of the most promising non-invasive technologies for the diagnosis of m... more Optical techniques are one of the most promising non-invasive technologies for the diagnosis of medical conditions. This work is devoted to the current state of the optical non-invasive diagnostics (OND), especially about instrumentation as well as methodological and metrological provision for this technology. In some details Laser Doppler Flowmetry (LDF) and Fluorescence Spectroscopy (FS) diagnostics methods are considered. The main conclusion is that it is necessary to solve the problems of metrological support OND devices of these types. It is also important to develop a methodology based on diagnostic criteria obtained from a relationship between a number of OND methods and others.

Background and objective The formation of reactive oxygen species (ROS) is associated with cardio... more Background and objective The formation of reactive oxygen species (ROS) is associated with cardiovascular disease (CVD). High dietary cholesterol can significantly alter the delicate balance between prooxidation and antioxidant defences leading to reactive oxygen speciesformationin the vasculature,without significant structural changes in tissue composition. We aimed to establish a methodology for the noninvasive assessment of skin fluorescent biomarkers in mice. Materials and methods C57/black/6 wild-type (WT; n = 25) male mice were subdivided to receive normal rodent chow (n = 11) or a high cholesterol diet (2% cholesterol; n = 14) for 20 weeks. Skin autofluorescence measurements were made on the backs of anaesthetized (1.5–2% isoflurane in oxygen) mice. A laser probe was used to make simultaneous measurements of: collagen, elastin, nicotinamide adenine dinucleotide, pyridoxine, flavins, lipofuscin and β-carotene. Results are expressed as group mean in arbitrary units (AU) ± stand...

The paper discusses the possibilities of noninvasive optical spectrophotometric diagnostic techni... more The paper discusses the possibilities of noninvasive optical spectrophotometric diagnostic techniques for registration and evaluation of changes in blood microcirculation processes at low level laser therapy. Preliminary results of experimental studies are presented. Visible stimulation of blood microcirculation was steadily observed only in the case of tissue heating on 0.8...1 C or more.

Photodiagnosis and Photodynamic Therapy, 2008

Thermal Treatment of Tissue: Energy Delivery and Assessment IV, 2007