M Yu Kirillin

Compression as a method for increasing the informativity of optical coherence tomography of biotissues

The efficiency of the mechanical compression of biotissues for improving the differentiation between pathological changes in the structure of a biotissue observed by the method of optical coherence tomography (OCT) is investigated. The effect of the compression in the OCT-images of samples of the human rectum affected by inflammation and carcinoma is studied ex vivo. It is shown that the use of compression makes it possible to differentiate between these pathological changes. To interpret experimental data, images of an inflamed part of rectum are modeled by the Monte Carlo method for different degrees of compression. The results of modeling agree qualitatively with the experimental data.

Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples

In this work, Monte Carlo simulation is used to obtain model optical coherence tomography (OCT) signals from a horizontally orientated blood layer at different stages of red blood cell (RBC) aggregation and sedimentation processes. The parameters for aggregating and sedimenting blood cells were chosen based on the data available from the literature and our earlier experimental studies. We consider two different cases: a suspension of washed RBCs in physiological solution (where aggregation does not take place) and RBCs in blood plasma (which provides necessary conditions for aggregation). Good agreement of the simulation results with the available experimental data shows that the chosen optical parameters are reasonable. The dependence of the numbers of photons contributing to the OCT signal on the number of experienced scattering events was analysed for each simulated signal. It was shown that the maxima of these dependences correspond to the peaks in the OCT signals related to the interfaces between the layers of blood plasma and blood cells. Their positions can be calculated from the optical thicknesses of the layers, and the absorption and scattering coefficients of the media.

Optical properties of mouse biotissues and their optical phantoms

Based on spectrophotometric measurements in the range of 700–1100 nm performed with the use of an integrating sphere, we have obtained absorption and scattering spectra of internal organs of mouse, as well as of aqueous solutions of India ink and Lipofundin, which are basic model media for creating optical phantoms of biological tissues. To retrieve the spectra of optical characteristics, we have used original formulas that relate the parameters of the medium with measured spectrophotometric characteristics and that are constructed based on classical analytical models of propagation of light in turbid media. As a result of comparison of spectra of biotissues and model media, we have developed a mixture of Lipofundin and India ink serving as mouse optical phantoms for problems of optical medical diagnostics.

Monte carlo simulation of signals from model biological tissues measured by an optical coherence tomograph and an optical coherence Doppler tomograph

The results of Monte Carlo simulation of optical coherence tomograph (OCT) signals from layers of a suspension of erythrocytes and an aqueous solution of Intralipid are presented. It is shown that the rear boundary of a layer of an erythrocyte suspension 0.5 mm thick is distinguished in the OCT signal for all the hematocrits considered (5, 10, and 35%). This is explained by fact that the greatest contribution to the signal is made by low-order scattered photons, which ensures good differentiation of internal inclusions and the rear boundary. In the case of the Intralipid solution, the main contribution is made by multiply scattered photons and the signal from the rear boundary is indistinguishable. Signals of an optical coherence Doppler tomograph (OCDT) from a plane-parallel flow of Intralipid between glass plates are also simulated. The effect of the Intralipid concentration on the velocity profile reconstructed from the OCDT signal is studied. It is shown that an increase in the Intralipid concentration leads to a shift in the maximum of the reconstructed velocity profile and to an stretching of the profile. The reason for these distortions is the contribution to the signal from multiple scattering. OCDT signals from a blood layer immersed in an optical phantom of skin are also simulated, and the distortions of the reconstructed profile are analyzed in relation to the depth of the layer.

Laser-ablated silicon nanoparticles: optical properties and perspectives in optical coherence tomography

Due to their biocompatibility silicon nanoparticles have high potential in biomedical applications, especially in optical diagnostics. In this paper we analyze properties of the silicon nanoparticles formed via laser ablation in water and study the possibility of their application as contrasting agents in optical coherence tomography (OCT). The nanoparticles suspension was produced by picosecond laser irradiation of monocrystalline silicon wafers in water. According to transmission electron microcopy analysis the silicon nanoparticles in the obtained suspension vary in size from 2 to 200 nm while concentration of the particles is estimated as 1013cm−3. The optical properties of the suspension in the range from 400 to 1000 nm were studied by spectrophotometry measurements revealing a scattering coefficient of about 0.1 mm−1 and a scattering anisotropy factor in the range of 0.2–0.4. In OCT study a system with a central wavelength of 910 nm was employed. Potential of the silicon nanoparticles as a contrasting agent for OCT is studied in experiments with agarose gel phantoms. Topical application of the nanoparticles suspension allowed the obtaining of the contrast of structural features of phantom up to 14 dB in the OCT image.

Liquid optical phantoms mimicking spectral characteristics of laboratory mouse biotissues

Optical phantoms mimicking optical properties of real biotissues in the visible and IR spectral regions are developed based on measurements of the spectral characteristics of ex vivo samples of laboratory mouse biotissues. The phantoms are composed of aqueous solutions of Lipofundin, Indian ink and red ink with different spectral characteristics. The deviations of the measured absorption and scattering coefficients of phantoms in the wavelength range 480 – 580 nm from the corresponding values for real biotissues do not exceed 25% and 2%, respectively. For phantoms in the wavelength region 580 – 880 nm, the deviations of the absorption coefficient do not exceed 40% and the deviations of the scattering coefficient do not exceed 25%. These values, in general, fall within the range of variations for different individual mice of one strain.

Gold nanoshells for OCT imaging contrast: From model to in-vivo study

We have investigated the effect of application of gold nanoshells with a 150 nm silica core size and 25 nm thick gold coating on optical properties of skin. We have analyzed the possibility of using these particles as a contrasting agent for optical coherence tomography (OCT). A set of Monte Carlo calculations was performed in order to simulate the images of skin before and after application of the nanoshells for a skin model close to that in vivo. We investigated the mechanisms of boundary contrasting between tissue layers with different optical properties in the presence of gold nanoshells on two-layer agar gel phantom. Gold nanoshells were also applied on the skin surface in vivo. Gold-silica nanoshells caused an increase in the intensity of OCT signal, brightness of the superficial part of the dermis, contrast between dermis layers and contrast of hair follicles and glands in the OCT image. The contrasting effects of the gold nanoshells lasted up to 24 hours of observation.

In vivo study of contrasting properties of gold nanoparticles for optical coherence tomography

We have investigated the effect of application of gold nanoparticles with a diameter of 50 nm and nanoshells with a 150 nm silica core size and 25 nm thick gold shell on optical properties of skin. We have analyzed the possibility of using these particles as a contrasting agent for optical coherence tomography (OCT). As the first step in the study, effects of gold nanoparticles after one application to skin were studied using OCT. Then we evaluated the effects of multiple applications of 50 nm gold nanoparticles to skin in 30-minute intervals. Biopsy of relevant skin areas was performed under local anaesthesia and samples for light and electron microscopy were prepared. Identification of skin layers on OCT images was made by comparing with histology. Application of gold-silica nanoshells caused increase in intensity of useful signal, brightness of the superficial part of the dermis and contrast between the superficial and deep parts of the dermis 30 minutes after application on skin. After 24 hours the changes in OCT images became more pronounced as the brightness of the superficial part of the dermis and the contrast between the superficial and deep parts of the dermis further increased. In addition, the border between the superficial and deep parts of the dermis became more distinct, continuous and well discernible, permitting to accurately differentiate these layers. Besides that, the application of nanoshells caused contrasting of hair follicles and glands. In order to give interpretation to the obtained experimental OCT-images of skin and understand the mechanisms of contrasting a set of Monte Carlo calculations was performed in order to simulate the images of skin before and after application of the nanoparticles for skin model close to that in the experiment. The results of the simulation exhibit good qualitative agreement with the experimental images and prove that the contrasting originates from the nanoparticles added while contrasting of hair bulb originates from the absence of nanoparticles in it with their presence in surrounding area.

Method of measuring blood oxygenation based on spectroscopy of diffusely scattered light

A new approach to the measurement of blood oxygenation is developed and implemented, based on an original two-step algorithm reconstructing the relative concentration of biological chromophores (haemoglobin, water, lipids) from the measured spectra of diffusely scattered light at different distances from the radiation source. The numerical experiments and approbation of the proposed approach using a biological phantom have shown the high accuracy of the reconstruction of optical properties of the object in question, as well as the possibility of correct calculation of the haemoglobin oxygenation in the presence of additive noises without calibration of the measuring device. The results of the experimental studies in animals agree with the previously published results obtained by other research groups and demonstrate the possibility of applying the developed method to the monitoring of blood oxygenation in tumour tissues.

Fluence compensated optoacoustic measurements of blood oxygen saturation in vivo at two optimal wavelengths

Non-invasive measurement of blood oxygen saturation in blood vessels is a promising clinical application of optoacoustic imaging. However, unknown spatial and spectral distribution of optical fluence within biotissue challenges precise multispectral optoacoustic measurements of blood oxygen saturation. The accuracy of the blood oxygen saturation measurement can be improved by the choice of optimal laser wavelengths. We propose the numerical approach to determine the optimal wavelengths for two-wavelengths OA measurements of blood oxygen saturation at various depths. The developed approach accounts for acoustic pressure noise, error in determination of optical scattering and absorption coefficients used for the calculation of the optical fluence, and diameter of the investigated blood vessel. We demonstrate that in case of an unknown (or partially known) fluence spatial distribution at depths between 2 and 8 mm, minimal error in the determination of blood oxygen saturation is achieved at the wavelengths of 658±40 nm and 1069±40 nm. We report on the pilot results of OA in vivo measurements of blood oxygen saturation using optimal wavelengths obtained by the proposed approach.