This PDF file contains the front matter associated with SPIE Proceedings Volume 6734, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing.

Possibility of submillimeter laser application for medical diagnostics is shown on change of state of lymphocytes, monocytes, and red blood cells caused by submillimeter laser radiation. The new diagnostic tests can be created for hematological and immunological clinics.

In this work, quality-limiting factors and optimum packing techniques in fiber bundles are studied, and they are applied to the design of imaging endoscopes in order to improve the image quality and achieve an optimum design, so that medical praxis based on these devices can be developed in a more reliable way. Quality-limiting factors in fiber bundles for medical imaging are analised. We find that leaky modes and interference between the optical fibers of the bundle have a close relationship with the length of the endoscope and opto-geometrical parameters of the fiber. They can be reduced using a steady state modes exciter and using a certain value of the distance between cores and the core diameter, respectively, as it will be studied. Optimum packing of the fibers is also very important to maximize the image area. We propose some structures and their efficiency is analised. It will be neccesary to reach an arrangement between core diameter, size of the cladding, and number of rings in the fiber bundle.

Optoacoustic conversion in diluted suspensions of medical and biological interest under the effect of laser pulses is considered. The various conversion regimes with moderate values of the laser fluence are studied both theoretically and experimentally.

The present paper is devoted to develop the universal scheme for biological object macrostructure spectral visualization. Correct realization of this task was done with 3D simulation of optical radiation propagation through multiple scattered media. Simulation was put into practice by Monte Carlo statistical technique. TracePro by Lambda Research Corporation with built-in Monte Carlo was chosen as the basic virtual environment. Obtained results are the base for creation an algorithm of optical superficial inhomogeneous registration and spatial localization in arbitrary structure tissues that may be used in noninvasive macro diagnosis.

Laser therapy, using low-energy laser radiation, is being more and more applied. The most applied technology is transcutaneous radiation of tissues by laser radiation. Originally, a direct action on a pathological site was mostly used, but recently more attention is given to reflexogenic areas, acupuncture points, and endocrine organ projection sites. The development of light-conductive engineering made it possible to practically apply intraorgan laser therapy. This technology is widely spread in gynecology, otorhinolaryngology, urology, gastroenterology, etc. Close to it are different versions of intratissue laser therapy (intraosteal, periosteal, myofascial). A special kind of laser therapy is laser hemotherapy. Depending on the techniques and protocol of its application, there are extracorporeal, intravascular, and supravenous ways of action. According to our comparative investigations, supravenous hemotherapy by its therapeutic efficacy and major medicinal effects can be well compared with intravascular laser hemotherapy. With good prospects and efficiency is laser therapy as a combination of laser and other physical factors. Magnetolaser therapy has been scientifically substantiated and practically applied so far. Theoretically and experimentally substantiated is a combined application of laser radiation and physical factors such as ultrasound, direct current field, vacuum, cryotherapy, etc. Experimental research and few so far clinical observations are indicative of prospects of a complex application of laser radiation and drugs. To improve light absorption, laser radiation is combined with different dyes. Photodynamic therapy, originally used in oncology, is applied today in treating different diseases. We showed a possibility of using a number of drugs possessing simultaneously photosensitizing properties to this end. Laser radiation significantly influences pharmacokinetics and pharmacodynamics of drugs, which gives reason to practically implement laser technologies, based on pharmacomodulating action of laser radiation, to practical medicine.

The ability to detect optical signals form a cellular target depends upon the amount of optical energy that can be generated by this target as the signal. Given that the sensitivity of optical detectors has some finite limit, further increase of the sensitivity of optical diagnostic methods requires increasing the energy of target-generated signal. Usually this energy is converted by the cellular target upon its optical excitation and is limited by many factors such as: cell and target damage thresholds, efficiency of excitation energy conversion, size of the target etc. All these put principal limitation on sensing small targets (like molecules) in living cells with any optical method because the energy that can be safely converted by the target into a signal is limited. To overcome this limitation and to improve the sensitivity of optical microscopy of living cells (and cytometry in general) we propose the concept of intracellular amplification of the optical signal. This concept includes two major steps. First, primary (pump) optical radiation interacts with the target (a probe molecule) to generate a transient target. Second, the transient target is sensed with additional optical radiation that does not interact strongly with primary target or the cell, and, hence, may have high enough energy to increase the signal from transient target even above the energy of pump radiation, which is limited by cell and target damage thresholds. We propose to use optical scattering from clusters of gold nanoparticles (the target) that are selectively formed in specific cells through antibody-receptor interaction and through endocytosis. To amplify this optical signal we propose to generate photothermal bubbles (the transient target) around those clusters. In experiments with water suspensions and with individual tumor K562 cells we have achieved optical signal amplification in individual cells (relatively to the scattering signal from intact cells): with gold nanorod intracellular clusters, 14.8 times, with photothermal bubbles, generated around those clusters, more than 100 times. Those signals were much higher than corresponding fluorescent signals and were obtained from living cells.

Laser-Induced-Autofluorescence (LIAF), White-Light-Remission (WLR) and Electrical-Impedance-Measurement (EIM) in combination with principal component analysis were used at first time for differentiation benign from malignant prostatic tissue in vitro. The used complex statistical processing of the data has shown a differentiation of benign and malignant prostatic tissue with a sensitivity of 93.8% and a specificity of 92.4%.

The optical properties of human stomach wall mucosa were measured in the wavelength range 400-2000 nm. The measurements were carried out using the commercially available spectrophotometer CARY-2415 with an integrating sphere. The combined method based on inverse adding-doubling and inverse Monte Carlo techniques was used to determine the absorption and scattering coefficients and anisotropy factor from the measurements.

Strong light scattering and absorption limit observation of the internal structure of biological tissue. Only special tools for turbid media imaging, such as optical diffuse tomography, enable noninvasive investigation of the internal biological tissues, including visualization and intravital monitoring of deep tumors. In this work the preliminary results of diffuse fluorescence tomography (DFT) of small animals are presented. Usage of exogenous fluorophores, targeted specifically at tumor cells, and fluorescent proteins expressed endogenously can significantly increase the contrast of obtained images. Fluorescent compounds of different nature, such as sulphonated aluminium phthalocyanine (Photosens), red fluorescing proteins and CdTe/CdSe-core/shell nanocrystals (quantum dots) were applied. We tested diffuse fluorescence tomography method at model media, in post mortem and in vivo experiments. The animal was scanned in transilluminative configuration by low-frequency modulated light (1 kHz) from Nd:YAG laser with second harmonic generation at wavelength of 532 nm or semiconductor laser at wavelength of 655 nm. Quantum dots or protein DsRed2 in glass capsules (inner diameter 2-3 mm) were placed post mortem inside the esophagus of 7-day-old hairless rats to simulate marked tumors. Photosens was injected intravenously to linear mice with metastazing Lewis lung carcinoma. The reconstruction algorithm, based on Algebraic Reconstruction Technique, was created and tested numerically in model experiments. High contrast images of tumor simulating capsules with DsRed2 concentrations about 10^-6 M and quantum dots about 5x10^-11 M have been obtained. Organ distribution of Photosens and its accumulation in tumors and surrounding tissues of animals has been examined. We have conducted the monitoring of tumors, exogenously labeled by photosensitizer. This work demonstrates potential capabilities of DFT method for intravital detection and monitoring of deep fluorescent-labeled tumors in animal models. The comparative analysis of conventional photosensitizer, fluorescent proteins and quantum dots has been carried out.

The objectives of these researches were to investigate the technical fundamentals of synthesizing high-strength biocompatible medical implants and tissue scaffolds made from nitinol or titanium using of Selective Laser Sintering/Melting (SLS/M). In particular, we had been identify the processing parameters and procedures necessary to successfully laser synthesize multi-material and functionally graded implants: the physical and mechanical properties, microstructure, and corrosion behavior of the resulting structures; the shape memory effect in porous layered nitinol structures made using laser synthesis. The comparative morphological and histological results of Selective Laser Sintering of porous titanium and nitinol implants are presented. Studies are conducted also on primary cultures of dermal fibroblasts and mesenchymal stromal human cells of the 4-18 passages. The principle possibility of long cultivating a bone marrow on the porous carrier-incubator from NiTi and titanium in vitro was determined. Sufficient understanding of laser synthesized titanium and nitinol structures to determine their suitability for future use as implants, resulting in superior tissue to implant fixation and minimally invasive surgical procedures, was developed.

The technical characteristics of the new three models of diffusion-cooled multichannel waveguide industrial CO₂ lasers excited with acoustic-frequency ac discharge are presented. The industrial lasers of this type have been developed for years at ILIT RAS. Generation of low (to 400 W) average power proved to be technically realizable through air cooling of the oscillator, which makes the laser performance even more attractive. The above lasers can be used to advantage in the laser processing systems intended for precision cutting of metallic (thickness to 10 mm) and non-metallic (thickness to 40 mm) materials; welding; surfacing and fabrication of parts from composite and metallic powder materials. The paper also provides the description and the technical characteristics of intellectual medical cardio-surgery laser systems of "Perfocor" family, developed at ILIT RAS for the transmyocardial laser revascularization (TMLR) which presents a promising method to cure the ischemic disease of heart. The clinical results (more than 800 operations) are presented. Owing to application of the TMLR technique the death rate at the A.N. Bakoulev Center is the lowest in the world. The project of a new CO₂ laser surgery plant "Khirurg" is discussed that would deliver up to 200 W power and is based on the model TL-300 with a system of biotissue diagnostics.

Influence of laser radiation on the skin is investigated in vivo. The exposure of blood to low-power laser light in the absorption range of haemoglobin leads to an increased intensity of the backscattered light, temperature and degree of oxygenation.

New approach in laser-optical diagnostic methods of cell metabolism based on visualization the local net of tissue blood vessels is proposed. Optical model of laser - tissue interaction and algorithm of mathematical calculation of optical signals is developed. Novel technology of local tissue hypoxia elimination based on laser-induced photodissosiation of oxyhemoglobin in cutaneous blood vessels is developed. Method of determination of oxygen diffusion coefficient into tissue on the base of kinetics of tissue oxygenation TcPO₂ under the laser irradiation is proposed. The results of mathematical modeling the kinetic of oxygen distribution into tissue from arterial blood are presented. The possibility of calculation and determination of the level of TcPO₂ in zones with the disturbed blood microcirculation is demonstrated. The increase of the value of oxygen release rate more than for times under the irradiation by laser light is obtained. It is shown that the efficiency of laser-induced oxygenation by means of increasing oxygen concentration in blood plasma is comparable with the method of hyperbaric oxygenation (HBO) at the same time gaining advantages in local action. Different biomedical applications of developing method are discussed.

The purpose of this work is studying a corneal asphericity change after a myopic refractive correction by mean of excimer lasers. As the ablation profile shape plays a key role in the post-op corneal asphericity, ablation profiles of recent lasers should be studied. The other task of this research was to analyze operation (LASIK) outcomes of one of the lasers with generic spherical ablation profile and to compare an asphericity change with theoretical predictions. The several correction methods, like custom generated aspherical profiles, may be utilized for mitigation of unwanted effects of asphericity change. Here we also present preliminary results of such correction for one of the excimer lasers.

Application of different phototechnologies (direct laser writing and frontal photopolymerization) for manufacturing of diffractive-refractive bifocal intraocular lenses has been described. Optically transparent photopolymer suitable for manufacturing hard and foldable optical components has been developed. The material and technologies allowed us to begin small-lot production in quantities enough for clinical testing of diffractive-refractive lenses MIOL-Accord. Clinical tests of the intraocular lenses demonstrated that all the patients are satisfied with their vision.

There has been growing interest in clinical application of laser-induced autofluorescence (LIAF) and reflectance spectroscopy (RS) to differentiate disease from normal surrounding tissue, including skin pathologies. Pigmented cutaneous lesions diagnosis plays important role in clinical practice, as malignant melanoma, which is characterized with greatest mortality from all skin cancer types, must be carefully discriminated form other colorized pathologies. The goals of this work were investigation of cutaneous hemoglobin-pigmented lesions (heamangioma, angiokeratoma, and fibroma) by the methods of LIAFS and RS. Spectra from healthy skin areas near to the lesion were detected to be used posteriori in analysis. Fluorescence and reflectance of cutaneous hemoglobin-pigmented lesions are used to develop criterion for differentiation from other pigmented pathologies. Origins of the spectral features obtained are discussed and determination of lesion types is achieved using selected spectral features. The spectral results, obtained were used to develop multispectral diagnostic algorithms based on the most prominent spectral features from the fluorescence and reflectance spectra of the lesions investigated. In comparison between normal skin and different cutaneous lesion types and between lesion types themselves sensitivities and specificities higher than 90 % were achieved. These results show a perspective possibility to differentiate hemoglobin-pigmented lesions from other pigmented pathologies using non-invasive and real time discrimination procedure.

One of the optical techniques applied in skin lesion investigations is reflectance spectroscopy of cutaneous tissues. Diffuse reflectance signals could be applied for absolute determination of absorption and scattering coefficients of biological tissue and give reliable results for wide range of wavelengths. However, light distribution anisotropy leads to significant influence over the reflectance spectra appearance depending on the used geometry. To obtain good reproducibility and repeatability of the results, one needs to fix carefully the geometrical conditions. We present skin reflectance spectra obtained at different angles and distances from tissue surface and discuss possible reasons for differences observed. In the case of small angles of incidence, we have significant losses of the backscattered light related to the anisotropy of the tissue and the intensity observed of the reflected signal is much lower than in the case of diffuse reflectance signal detected at higher angles. In the case of direct contact between skin surface and end tip of the fibers great reduction of the short wavelength component is observed. The appearance of higher intensity blue signal as the distance between end tip of the optical fibers and skin surface is increased could be related to the specular component of the reflectance spectra. An optimum distance exists where the registered signal has the greatest value, which is related to the specific parameters of the optical fibers used, such as diameter and optical aperture.

The problem of retrieval of homogeneous spherical particles characteristics by the data on the intensity of scattered light is considered. To solve this problem the high-order neural networks method is used. The algorithms to determine radius and refractive index of particle using the multidot high-order neural networks are proposed. The nets to retrieve particle's radius and refractive index by the data on the intensity of scattered light in a limiting range of available for measurement angles are constructed. The neural networks are trained in the range of radius from 0.5 up to 15.5 microns and refractive index from 1.02 to 1.2, respectively. Dependence of the retrieval errors on particle characteristics and the neural network structure is estimated.

The removal of tattoo pigments by laser energy is effected through a process of selective photothermolysis. Dehydration and optical immersion based on refractive index matching of scattering centers with that of surrounding matter through introduction of an exogenous index-matching agent can improve laser tattoo removal by providing increased efficiency of laser delivery to embedded ink particles and enabling the use of shorter wavelength visible lasers more effective on certain inks. Effectiveness of a method of accelerating penetration of the index-matching compounds by enhancing skin permeability through creating a lattice of micro-zones of limited thermal damage in the stratum corneum was studied. As optical clearing agents 100% and 88%-aqueous glycerol solutions were used. The effect of stratum corneum perforation on the rate of the immersion clearing of skin was studied. Dynamics of refractive index alteration of glycerol solution during its interaction with skin samples was monitored. Improvement of tattoo visualization was observed. The results of the experiments have shown that the lattice of island damage method the is effective for transepidermal delivery of optical clearing agents and could be used successfully in in vivo conditions for the enhancement of optical clearing of treated skin area and as enabling improvement of laser tattoo removal.

Transmembrane transfer of medicines are investigated under the action of laser radiation. Regulation of antibiotics transport across membranous model of skin with the use of dimethylsulfoxide addition into hygrogel matrix, modification of laser spectral parameters is achieved.

Intravenous laser irradiation of blood (ILIB) by helium-neon laser (HNL) with &lgr;=632.8 nm, 2.5-4.5 mW at the light guide outlet was employed to investigate ILIB influence on blood oxygen transport (BOT), hydro-ion balance for normal rabbits and after modeling of local ischemia of brain (LIB). Marked improvement of disturbances typical for ischemia was revealed for both hydro-ion balance characteristics and BOT parameters such as oxygen tension (p_vO₂), oxygen hemoglobin saturation (s_vO₂), p_vO₂ of blood under its 50% saturation by O₂ (p50) and tendency was found to their normalization. To identify the molecular photoacceptors and the mechanisms of primary photoreactions the spectral data were used both in visible and infrared regions. On the basis of spectral analysis hemoglobin was discussed as a possible photoacceptor when blood is irradiated with HNL radiation. Variations in the redox properties of respiratory chain components were considered as primary mechanisms of light action on photoacceptor molecules that initiated a cascade of secondary reactions controlling cellular homeostasis parameters.

Cell structure, shape, and size distribution are characterized by optical measurement of normal peripheral blood granulocytes in a cell suspension as applied to a cell discrimination by the solution of the direct and inverse light-scattering problems in scanning flow cytometry (SFC). The distribution laws of the cell and nuclei sizes are estimated. A morphometric model of a segmented neutrophilic granulocyte is constructed on the base of the gained data. An interrelation between the cell and nucleus metric characteristics is deduced. The obtained interrelation allows decreasing a number of independent parameters of the cell model to adapt it to the real-time discrimination of the cells. The findings can be used as input parameters for the solution of the direct and inverse light-scattering problems in SFC-dispensing with a costly and time-consuming immunophenotyping of the cells.

In an experiment on animals, the efficacy of a new technique of photodynamic therapy based on Fotolon ointment phonophoresis was demonstrated.

The results of an irradiation of sensitized and non-sensitized tumors Pliss lymphosarcoma are presented in the paper. The experimental data and the theoretical calculations show, that hemoglobin can be considered as a primary agent, the photoexcitation of which induces cytotoxic reactions resulting in a tumors destruction without an exogenous singlet oxygen photosensitizer. Several mechanisms of a laser action on biological tissues, which can hypothetically influence on PDT efficiency, are discussed in the paper.

The use of optical techniques in medical praxis allows practitioners to improve their tools. This improvement is realized in two main aspects, treatment and characterization of biological tissue. The former deals with methods like Photodynamic Therapy (PDT), Low Intensity Laser Therapy (LILT) or Hyperthermia. Tissue characterization by optical means is more challenging. The idea is to obtain images from biological tissues with a non-contact, non-invasive and safe procedure. The drawbacks of conventional imaging techniques, like X-Ray with its ionising radiation or ultrasound with the needed contact, are then avoided. Some of these optical techniques are for instance Confocal Microscopy or Optical Coherence Tomography (OCT). The inclusion of the analysis of light polarization can increase the contrast in these images. In this work, polarization information via the Mueller matrix of the target tissue in 2D is proposed as an improved way of characterization. This matrix contains all the polarization properties of tissue, including depolarisation, so a more complete analysis can be carried out. A polarimeter, composed by linear polarizers and rotators, as long as a CCD camera, is proposed to measure 2D Mueller matrix in concrete points of a biological tissue. The importance of these diagnosis methods is crucial in preliminary detection of diseases, like cancer.

The advantages of applications of diode-pumped solid-state laser based on thulium-doped potassium yttrium tungstate and Raman laser with the wavelengths of &lgr;~2 &mgr;m and &lgr;~1.6 &mgr;m correspondingly for local coagulation of surface tissue defects are considered.

Stochastic models of multilayer tissue and low-coherence interferometric signals are considered. The extended Kalman filtering method is investigated applied to dynamic evaluating layer borders of multilayer tissues in Optical Coherence Tomography (OCT). Increased resolution of layer borders is provided by direct transforming input fringe signal samples series to dynamic estimates of fringe amplitude and local envelope maximum positions. Results of experimental estimates of the method resolving power in the case of partially overlapped envelope peaks presented and discussed.

The treatment of blood with low intensity laser irradiation has become popular in a variety of clinical applications due to its anti-inflammatory, biostimulative and immune-stimulatory effects etc. Laser blood irradiation with infrared and red laser sources have the potential for stimulating antioxidant enzymes activities. At present study the influence of red and infra-red laser irradiation at different doses on superoxide dismutase (SOD) activity of peripheral blood lymphocytes was investigated in vitro. Suspensions of human lymphocytes (concentration of cells 1x10⁶ cells/ml) were irradiated with red (670 nm) and infrared (980 nm) therapy lasers at different light doses (0-600 J/sample) and light power (4,5 and 15 mW for red; 50 and 500 mW for infrared) at 20°C. It is revealed doze-depended effect of red and infra-red laser irradiation on superoxide dismutaze activity of peripheral blood lymphocytes. The SOD activity, first of all, depends on irradiation time, but not on intensity or wavelength of irradiation. These data can explain the positive medical effects of a laser blood irradiation. The obtained results confirm a hypothesis that laser irradiation with the different wavelength characteristic (red and infra-red light ranges) reveals a stimulating effect on SOD - antioxidant defence system enzyme in peripheral blood lymphocytes.

Laser fluorescent analysis has been used for assessing the spectra of normal and nuclear cataract lens fluorescence in vivo. Spectral criterion (index of opacity) was developed for objective differentiation of cataract's stage. Contribution of ascorbic acid into spectrum of cataract lens fluorescence was analyzed.

Assessment of carboxyhemoglobin photodissociation performed at solution of whole human blood. At the range 550-585 nm we detected maximal efficacy of carboxyhemoglobin dissociation corresponding to Q-electron transition at 570 nm.

We have developed and researched a new method of modal phase tomography for diagnostics of human eye aberrations. The technique of restoration permits separating the contributions of different elements of the eye to the total aberrations. The results of numerical researches and modeling experiment are presented.

The efficiency of splitting of renal rocks is studied with the usage of four schemes of the laser construction, generating momentums of microsecond duration. The dependence of deleting of the concrete renal rock substance on spectral content of radiation of microsecond duration in the range of 460-1064 nm has been established.