We describe applications of silica (core)/gold (shell) nanoparticles and ICG dye to photothermal treatment of
phantoms, biotissue and spontaneous tumor of cats and dogs. The laser irradiation parameters were optimized by
preliminary experiments with laboratory rats. Three dimensional dynamics of temperature fields in tissue and
solution samples was measured with a thermal imaging system. It is shown that the temperature in the volume
region of nanoparticles localization can substantially exceed the surface temperature recorded by the thermal
imaging system. We have demonstrated effective optical destruction of cancer cells by local injection of
plasmon-resonant gold nanoshells and ICG dye followed by continuous wave (CW) diode laser irradiation at
wavelength 808 nm.
We describe an application of plasmonic silica/gold nanoshells to produce a controllable laser hyperthermia in tissues with the aim of the enhancement of cancer photothermal therapy. Laser irradiation parameters are optimized on the basis of preliminary experimental studies using a test-tube phantom and laboratory rats. Temperature distributions on the animal skin surface at hypodermic and intramuscular injection of gold nanoparticle suspensions and affectations by the laser radiation are measured in vivo with a thermal imaging system. The results of temperature measurements are compared with tissue histology.
This paper deals with the problem of using semiconductor laser radiation (wavelength 810 nm) for healing skin and
mucous cancer of small animal. Opportunities of using different types of lasers for clinical applications under
oncological diseases of skin and oral mucous have been analyzed. We determined power densities and duration of laser
irradiation for different types of tumors. IR thermograph was used for noninvasive temperature monitoring in the area of
tumor localization. For noninvasive measuring and registration of spatial distribution of radiation temperature of
investigated objects, we used IR Imager IRISYS 4010 Infrared Integrated System Ltd (UK).
Traditional biological and chemical methods for pathogen identification require complicated sample preparation for
reliable results. The process of identification of malignant and non-malignant growths is not easier. Optical scattering
method may be useful to detect bacterial cells in suspension and to determine malignant and non-malignant growths.
Orthogonal Zernike moments of different order were used to analyze speckle patterns, which are formed by irradiated
object of interests. Being irradiated by light every object forms a unique speckle pattern. Due to the originality of every
single speckle pattern they may be used to obtain some information about object that formed this pattern.
A new interference scheme of low-coherent interferometry was considered. This interference system does not use
a special supporting beam. An object is lighted up by optical field directly from source of light. Back-scattered
radiation is put to correlation analysis using Michelson scanning interferometer. Such unsupported interference
system has a number of advantages, e.g. conducting experiments in vivo.
A comparison of spatial sensitivity of OCT and HRT tomographs resolution was made during identification of
local inhomogeneity in presence of nanoshells and nanorods in bio-phantoms and bio-tissues. Plasmon-resonant
gold nanoparticles can be used as a new class of contrast agents in OCT diagnostics.
The theoretical part of our study was to simulate the backscattering signal related to the process of
electromagnetic wave propagation through a system of discrete scattering particles with consideration the
effects of different scattering multiplicity. By using the computer Monte Carlo simulations, we calculated
the spectra of collimated transmission, diffuse forward and back scattering for the systems of gold spherical
particles and shells.
Light-induced inactivation of dynamic response of somatic frog nerve on electrical pulsed excitation was study ex vivo. The light-sensitive Indocianin Green has been used on photodynamic induced inactivation of the processes generation nerve pulses. Inactivation of consequence action potential of somatic frog nerve using excitation of electrical pulsed was achieved by irradiation with diode laser light in a IR spectral region (λ=810 nm, P~1W/cm2) in the case of Indocianin green. It was discovered that Indocianine green decrease of the amplitude compound action potential of the ensemble neurons. Experiments show effective destruction of cancer cells of ear, mouth and skin by local injection of plasmon resonant gold nanoshells and semiconductor laser (810 nm) irradiation. For destruction such tumors pulse duration was not less than 1microsecond and pulse separation 10 at average power density 1-3 W/sm2 and energy density 100-200 J/sm2
Nowadays the artificial neural network (ANN), an effective powerful technique that is able denoting complex input and
output relationships, is widely used in different biomedical applications. In present study the applying of ANN for the
determination of characteristics of random highly scattering medium (like bio-tissue) is considered. Spatial distribution
of the backscattered light calculated by Monte Carlo method is used to train ANN for multiply scattering regimes. The
potential opportunities of use of ANN for image reconstruction of an absorbing macro inhomogeneity located in topical
layers of random scattering medium are presented. This is especially of high priority because of new
diagnostics/treatment developing that is based on the applying gold nano-particles for labeling cancer cells.
We describe applications of colloidal gold nanoparticles and silica/gold nanoshells to photothermal therapy and X-ray diagnostics of cancer exemplified by spontaneous tumor of cats and dog. It is shown that the contrast of X-ray images of a cat mammalian tumor can be increased significantly by injection of 3-5-nm gold nanoparticles. We also present preliminary results of a complex approach to treatment a dog mouth cavity melanoma by using immunotherapy together with laser photothermolysis enhanced with silica/gold nanoshells.
The study is aimed at evaluation of diagnostic potential of plasmon-resonant nanoparticles as contrast agents for various techniques based on backward diffuse light scattering from biotissues. We consider the theoretical spectra of diffuse backscattering from a plane layer of gold nanospheres embedded into a plane layer of scattering dielectric spheres that mimic a strongly scattering sample of a biotissue. It is shown that the backscattering spectra contain information about 35-nm gold spheres provided the location depth is less than 600 mkm. The simulated color characteristics resemble the measured characteristics of a rat skin. The measured diffuse reflection spectra of 35-nm gold colloid are close to the spectra of 70/15-nm silica/gold nanoshells although the plasmon resonance wavelengths (520 and 630 nm) differ significantly.
The method of so-called laser interferometric chromoretinometry based on the use of laser sources with different colors of light in retinometer is considered. The results of application of this method for determination of retinal visual acuity (RVA) at various diseases of eye and for diagnostics of the earliest age pathological changes of a crystalline lens are discussed. Transformation of scatterers structure in the eye at age pathological changes of a crystalline lens results in essential changes in scattering of light angular spectra. Intensity of the scattered light depends on the wavelength, hence, the decrease of contrast of intererence fringes for different wavelengths is different. The dependence of fringe contrast on the wavelength can be used for in vivo diagnostics of crystalline lens pathology.
The new optical system for interference determination of retinal visual acuity (RVA) based on the use special diffraction elements random phase screens with two identical microstructures is offered. The system includes low coherence sources with quasi-monochromatic red, green, and blue light colors and special diffraction optical element that creates on patient retina an interference pattern with parallel fringes of a particular color. The restuls of the system application in diagnostics of the earliest age patholgocal changes of the lens of eye are discussed. 42 patients (74 eyes) with the initial shapes of cataract and control group without pathology are surveyed. It is established, that at the patients with initial shapes of cataract the values of RVA by green and dark blue colors are lower than it by red, and at the patients without pathology these values coincide. Intensity of scattering light depends on the wavelength, and the interference pattern contrast at the presence of lens inhomogeneities is variable for different wavelengths. Hence, the given system can be used for diagnostics of the earliest age pathological changes in a lens.
The scattering spectra of low-absorptive disperse media are not much researched. It is stipulated by the same difficulties: in experiments, the theoretical investigations had low precision and some errors and the most precise Monte-Carlo method until quite recently was difficult to use in that aim in view of the large time expenses. However, that theme required investigation since the scattering spectra are very informative and make it possible to describe the internal structure of the studied object. It is important in researches of biotissues when the scattering spectra are the means of effective non-invasive diagostics. In our study the system of spherical particles which sizes are comparable with radiation wavelength that then applied to the tissue of eye lens, the internal parameters of which were changing depending on the pathology cases were modeled. And the results of theoretical investigations of scattering spectra of these objects obtained by the Monte-Carlo simulation are presented.
Theoretical and in vitro and in vivo experimental study of spectral and polarization characteristics of the human and rabbit eye tissues are presented. The possibility of control of optical properties of eye cornea, lens and sclera is discussed and realized experimentally for glucose solution as the refractive index matching factor.
Laser light radiation scattered by the system of spheres with various parameters was theoretically investigated by using of the Mie theory of electromagnetic scattering by a single sphere. The calculations were performed for systems of particles whose coordinates were specifically realized in random fashion according to the specified probabilities defined by the approximation of hard spheres. The parameters of model are the same as in the eye lense biotissue and were carried out by using of medical data about internal structure of men lens and some animals. In general the studied model presents the system of homogeneous spherical particles which are randomly distributed in the layer of thickness. We study the optical properties such as scattering effective cross-section and function of correlation in different models.
A rigorous multiple scattering wave theory for investigation of 2D photonic crystals is used. The use of translation properties of Bessel functions reduces the scattering problem to the linear system. This method is able to provide angular dependence of scattering intensity of the samples of structures formed by different number of circular rods. Some biological tissues, for example the optical tissues of eye-cornea and sclera, can be considered as natural photonic crystals.
Theoretical investigations of laser light radiation scattered by eye lens model as a system of spheres with various parameters were performed on the base of Mie theory of electromagnetic scattering by a single sphere. The calculations were performed for systems of particles whose coordinates were specifically realized in random fashion according to the specified probabilities defined by the approximation of hard spheres. The modeling of lens biotissue was carried out by using of medical data about internal structure of lens of human and some animals. In general the researchable model presents the system of homogeneous spherical particles those are randomly distributed in the layer of thickness. We study the optical properties such as scattering effective cross-section and function of correlation in different models.
The theoretical investigations of laser light radiation scattered by eye lens model as a system of spheres with various parameters in case of gaussian wave were performed on the base of Mie theory of electromagnetic scattering by a single sphere and by using Bromwich formulation. The amplitude matrix of light scattering, the intensity distribution of scattered light are received. The contrast analyses of obtained intensity distributions in dependence on size and amount of scatterers were carried out. The optical constants and dimensions of the particles were varied in a range of values corresponding to the normal and pathological lenses.
This paper deals with the problem of calculating the color characteristics of light scattered by disperse systems. Multiple scattering effects were taken into account.
The inclusion of radiation polarization considerably extends the sensitivity and the potentials of optical coherence tomography. The recorded signals are however skewed by using wide-band light sources and polarization sensitive elements, as well as by frequency dispersion of the objects under study. It is essential for such layered system with spatial anisotropy as eye cornea and sclera.
This paper is concerned the problem of calculating the polarization and spatial characteristics of laser radiation scattered by the eye lens. In calculations, a complete general solution of the problem of interactive electromagnetic scattering by clusters of arbitrary configured nonidentical spheres was used. The light scattering matrix, the image of a speckle structure of scattered radiation, the intensity distribution are received. The optical constants and dimensions of the particles were varied in a range of values corresponding to the normal and pathological lens. The modeling results are compared with the previously reported experimental indicatrixes of the eye lens.
The dependence of reflectance on the scattering coefficient value and the distance between the emitting and receiving fibers are analyzed using Monte Carlo simulation technique. The preliminary results of in vivo measurements of the reflectance at 830 nm of the human skin immersed by various oils and lotions are described.
This paper deals with the problem of calculating the polarization and spatial characteristics of laser radiation scattered by the eye tissues. Multiple scattering effects simultaneously with the degree of near order for scattering particles were taken into account.
The Monte-Carlo method was used to study the effect of multiple light scattering on the medium's polarization characteristics. The influence of the scattering system parameters and experimental conditions on the results of LSM measurements were estimated. Calculation was performed for a monodisperse system of spherical particle. The scattering medium was enclosed in a spherical and a cylinder cells. The influence of cell wall thickness and light reflection at the medium-glass and glass-air interfaces was regarded. Various parameters of incident beam, cell diameter and scattering particles dimensions were employed for calculations.
The theoretical model of a human eye lens is presented. This model accounts effects of the spatial interaction of scatterers arising due to existence of closely packed system of particles and the complexity of refractive index of their material. The calculations of transmission and scattering spectra for a monodispersive system of scatterers were done using Monte-Carlo method. The influence of absorption on transmission spectra formation was studied.
Theoretical and computer modeling approaches, such as Mie theory, radiative transfer theory, Monte Carlo simulation method were applied for tissue optics analysis in a process of its optical clearing due to refractive indices matching. CW transmittance and forward and backward scattering measurements were used for tissue structural and optical properties monitoring. As a controlled tissue samples of the human sclera were taken. As a chemical applicator-controller osmotically active trazograph solution was used. The scleral absorption and scattering spectra as well as diffusion coefficient describing the samples of the human sclera permeability to trazograph wer experimentally estimated. Presented results are general and can be applicable for description of many other fibrous tissues.
This paper deals with the problem of calculating the polarization and spatial characteristics of laser radiation scattered by the eye lens. The light scattering matrix (LSM) and angular dependencies of the LSM elements were obtained. Multiple scattering effects simultaneously with the degree of near order for scattering particles were taken into account.
Investigation of the polarization characteristics of scattered light can be effectively used for diagnosis of biotissues and bio-objects. Usually the whole indicatrices of scattered light can not be measured in vivo. So the investigation of polarized backscattered light is of great interest. The high concentration of scatterers in such objects requires the multiple scattering effects to be accounted for. In this work the Monte-Carlo method was used to describe the multiple scattering of polarized light. Trajectories of each migrating photon were traced by this method. Probability density of scattering directions are determined according to the Mie formulas with accounting for the polarization of each photon. As a result, the Stokes vectors of scattered light were calculated. So, we have determined the changes of polarization characteristics caused by the variations of the dimensions and concentrations of scatterers and by the geometry of medium. The influence of the order of scattering on the depolarization of scattered light also have been investigated. We present the patterns of spatial distribution of intensities backscattered polarized light. Calculations were performed for the systems of isotrope spherical scatterers and the obtained results were compared with the experimental data of measurement in the cross-polarized channel described in.
It is shown experimentally and theoretically that due to interaction of totally or partially coherent light beams with such tissues as the human eye sclera and skin which undergo the refractive indices matching the collimated and total transmission, diffuse reflection and speckle structure of transmitted beams are changing in accordance with transition from multiple to low-step scattering. The scleral samples in a final stage of tissue optical clearing have the same properties as an optical retarder.
Photoacoustic spectroscopy is powerful method of investigation of absorption spectra of scattering media. This method was successfully applied for investigation of different biotissues. However the multiple scattering is essential in these media. It disturbs the output photoacoustic signals. So it is necessary take this phenomenon into account. The purpose of our work is to analyze the variations of photoacoustic signal versus the multiplicity of light scattering. Calculations are held for the model monodisperse spherical particles. Mie theory was applied to describe scattering by single spherical particle. The case of Gaussian profile beam was considered. Monte- Carlo method was used to calculate the photons trajectories in three dimension space. Such events as photon absorption, scattering and reflection from the sell walls was evaluated by random numbers with appropriate probability density. Angular dependence of probability density of the photon scattering is determined in terms of Mie theory for depolarized light. So we define coordinates of photon's collision and absorption points. It enables us to determine the spatial distribution of the points of photon absorption, which depends on the shapes of scattering volume and beam profile. These calculations were made for the model of former elements of blood. It was shown that the multiple scattering varies the absorption profile of the beam. Since multiplicity of light scattering depends on the wavelength of incident light, then absorption spectrum is disturbed. The depth of light penetration into the medium appears to be essentially smaller in the case of short wavelengths.
We have used, in our paper, the Monte Carlo method to study the multiple light scattering effect on the medium polarization characteristics. We have estimated the influence of a scattering system parameters and experimental conditions on the LSM measurement results. In our model a monodisperse system of spherical particle was used. The scattering substance was considered to be placed in a cylinder cell. Calculations were conducted for various parameters of incident beam, cell diameter and scattering particles dimensions. The calculations were performed for three values of particle diameters and different concentrations.
Theoretical and computer modeling approaches, such as Mie theory, radiative transfer theory, diffusion wave
correlation spectroscopy, and Monte Carlo simulation were used to analyze tissue optics during a process of
optical clearing due to refractive index matching. Continuous wave transmittance and forward scattering
measurements as well as intensity correlation experiments were used to monitor tissue structural and optical properties. As a control, tissue samples of the human sclera were taken. Osmotically active solutions, such as Trazograph, glucose, and polyethylene glycol, were used as chemicals. A characteristic time response of human scleral optical clearing the range 3 to 10 min was determined. The diffusion coefficients describing the permeability of the scleral samples to Trazograph were experimentally estimated; the average value was DT'(0.960.5)31025 cm2/s. The results are general and can be used to describe many other fibrous tissues.
Theoretical and computer modeling using Mie theory, radiative transfer theory, diffusion wave correlation spectroscopy, Monte Carlo simulation technique were applied for human sclera optics analysis in a process of its optical enlightening caused by osmolitically active chemicals administration.
In the work, behavior of the elements of light scattering matrix (LSM) is investigated during the process of aggregation of proteins of the eye lens. We consider a system of spherical scatterers as a model of the lens. The Monte-Carlo method is used to trace migration and scattering of photons in a medium. Light scattering on the particles is described by the Mie formulas. We investigate influence of the multiple scattering on spatial and polarization characteristics of the scattered laser light accounting for the given geometry of the experiment and obtain angular dependencies of the LSM elements. Also the angular dependencies of weights of different orders of scattering are obtained. It is shown, that for small particle systems the influence of multiple scattering has a maximum for the scattering angle equal to 90 degrees. Finally, we discuss light depolarization in the lens.
Changes of light scattering matrix elements during the aggregation process are investigated. It is shown that during the aggregation the depolarizing ability of protein solution increases for the particles smaller than wavelength and it may have a minimum for the larger ones. Light depolarization is estimated as a function of the measurement duration and of the width of particles distribution by size.
Theoretical and computer modeling approaches, such as Mie theory, radiative transfer theory, diffusion wave correlation spectroscopy, Monte Carlo simulation method were applied for tissue optics analysis in a process of its clearance. CW collimated transmittance and forward scattering measurements as well as intensity correlation experiments were used for tissue structure and optical properties monitoring. Conrolled tissue samples of the human sclera were taken. A chemical applicator-conrollers Trazograph, glucose and polyethileneglycol solutions were used. On the base of sclera samples clearance investigation the general principles of tissue optical and structural parameters controlling were established.
Transscleral laser microsurgery has gained wide acceptance recently. Many problems in this field are due to laser beam decay in an optically nonhomogeneous sciera. The sciera light transmission in defined by scattering processes on its fibers. Because of high density in the arrangement of sciera fibers, the phenomena of interferential interaction between scattered radiation and multiple scattering are essential. Our paper is aimed at the theoretical and experimental validation of light scattering decrease on collagen fibers by substituting the sciera base substance with substance exhibiting higher refraction index. As a model of sciera, system of long dielectric cylinders was chosen, which were surrounded by isotropic base substance with lower refraction index. The fibril diameters are varied from 10 to 100 nm. The indexes of refraction for the fibrils and embedding substance differ appreciably from each other and are equal2, respectively) to 1,47 and 1.345. The thickness of sciera is I mm. The statistic characteristics of spatial arrangement of fiber centers were described at an approximation of exduded volume. The scattering amplitude function for a single cylinder was calculated using Mie theory. Under calculation it was assumed that the axes of all the fibers are parallel to the sciera surface and their orientation in this plane is random. Two complex coefficients for waves, polarized in parallel and normally to the fiber axes, were found by means of method describing the propagation of coherent waves through random systems. According to this approach, scattering medium is represented as homogeneous but a having new effective refraction index. The imaginary part of the index takes into account energy extinction due to scattering.
The basic principles of light scattering methods which should be very useful for ophthalmic disease diagnostics and monitoring are discussed. As an example a human eye lens tissue was considered. Angular-dependent scattering spectra and scattering matrix elements M12, M33, M34 and M44 are suggested as informative parameters for eye lens aging and cataract monitoring.
We performed this work to estimate the errors of the device for measurement of light scattering matrices (LSM). The scheme of a laser polarizational nephelometer with polarization modulation by the phase plates rotating with a speed ratio of one to five was taken for analysis. For this scheme the influence of the adjustment errors on the LSM elements of different test objects was evaluated by the Monte-Carlo method, and we have found the matrix of empty space to be the most sensitive to the errors. Dependencies of the matrix error upon the different adjustment parameters have been plotted for the matrix of empty space. Also we have studied dependency of the errors from the intensity of scattered light and the distortions in the registration unit. We also analyzed the modulation of the polarization state by rotation of the phase plates. We studied the condition number [cond(C)] of the matrix of conversion of the input signal Fourier spectrum to LSM was under investigation. Dependencies of cond(C) versus the initial orientation of the phase plates axis and the phase shift values were investigated.
Cornea anisotropic properties have been investigated experimentally by Mueller matrix technique. The system of the plane anisotropic layers has been used as an optical model of the cornea. In this model we consider every layer to be a closely packed system of long cylinders. Jones's transmission matrices of the above mentioned multilayer anisotropic system were calculated using transfer matrix 4 X 4 method. The multilayer systems with different ordering of layer's optical axis were analyzed. We have obtained spectral dependencies of limit values of linear and circular dichroism and birefringence from cornea fiber orientation. Mueller matrices of rabbit cornea were measured experimentally. Then we turn from the experimental Mueller matrix to Jones matrix to reveal clearly the cornea anisotropy. This transition is correct for the depolarization-free objects. Analyzing the cornea experimental Muller matrices by the depolarization criterion method we conclude that cornea has a negligible depolarization. Theoretical and experimental results appear to be in good agreement.
There are six known inequalities which connect the elements of light scattering matrix (LSM). Analysis of the inequalities shows that the region of permissible values of the elements in the upper left quadrant of LSM has a form of tetrahedron in the space of (M12, M21 M22). In this work we have investigated regions of localization of the LSM elements corresponding to the basic types of optical objects.
The relationships between Mueller matrix elements are considered. The correctness of their application as a criterion for consistency of experimental data and for the estimation of depolarizing ability of real objects are analyzed. Experimental errors have been assessed by means of numerical simulation.
Optical models of crystalline lens were analyzed, to increase understanding of high transparency and loss of it with aging and for pathology tissue. Experimental and calculated human crystalline lens spectra in a wide range of wavelengths are presented. Calculations were made for the model of short-term- order scatterers, taking into account interference effects of scatterers and specific features of absorbing species, such as protein-bound tryptophan, kynurenine, and age-related chromophores leading to generalized yellowing of the lens proteins. Satisfactory qualitative coincidence of calculated spectra with spectrophotometric data for isolated human lens is shown. Measured angular dependencies of scattering matrix elements are sensitive to modification related to aging and cataract appearance.
Several alternative solutions of the inverse problems of quantitative analysis of a wide range of disperse systems by means of elastic light scattering method are discussed. The possibilities are considered for the optimization of the spectroturbidimetric method as a tool in studying of the structurally complex biological and synthetic suspensions with due consideration for the unavoidable restrictions on spectral interval width and the body of a priori information for real systems.
Scattering methods are widely used for diagnostics in biology and medicine and the analysis of the experimental
results very often requires accounting for concentration effects.' The most simple model allowing to analyse the
scattered light interference is a system of densely packed hard spherical particles.
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