Quantification of attenuation and speckle features from endoscopic OCT images for the diagnosis of human brain glioma.

Application of optical coherence tomography (OCT) in neurosurgery mostly includes the discrimination between intact and malignant tissues aimed at the detection of brain tumor margins. For particular tissue types, the existing approaches demonstrate low performance, which stimulates the further research for their improvement. The analysis of speckle patterns of brain OCT images is proposed to be taken into account for the discrimination between human brain glioma tissue and intact cortex and white matter. The speckle properties provide additional information of tissue structure, which could help to increase the efficiency of tissue differentiation. The wavelet analysis of OCT speckle patterns was applied to extract the power of local brightness fluctuations in speckle and its standard deviation. The speckle properties are analysed together with attenuation ones using a set of ex vivo brain tissue samples, including glioma of different grades. Various combinations of these features are considered to perform linear discriminant analysis for tissue differentiation. The results reveal that it is reasonable to include the local brightness fluctuations at first two wavelet decomposition levels in the analysis of OCT brain images aimed at neurosurgical diagnosis.

Influence of optical clearing agents on the scattering properties of human nail bed and blood microrheological properties: In vivo and in vitro study.

Optical clearing agents (OCAs) are substances that temporarily modify tissue's optical properties, enabling better imaging and light penetration. This study aimed to assess the impact of OCAs on the nail bed and blood using in vivo and in vitro optical methods. In the in vivo part, OCAs were applied to the nail bed, and optical coherence tomography and optical digital capillaroscopy were used to evaluate their effects on optical clearing and capillary blood flow, respectively. In the in vitro part, the collected blood samples were incubated with the OCA and blood aggregation properties were estimated using diffuse light scattering techniques. The results indicate that OCAs significantly influence the optical properties of the nail bed and blood microrheology. These findings suggest that OCAs hold promise for improving optical imaging and diagnostics, particularly for nail bed applications, and can modify blood microrheology.

Conditions of acceleration and deceleration of the cancer cell growth under osmotic pressure.

In this paper, we study a pattern formation in the epidermal layer of skin during tumor development and appearance of a binary surface consisting of healthy and cancer cells forming Turing patterns under external osmotic pressure. The basic methodology of introducing the external influences, for example, time-targeted drug therapy or radiation exposure, influence of electromagnetic fields, laser radiation or other tumor-targeting physical influences act differently in different phases of the cell cycle. In some cases, this can lead to a slowdown in the growth of cancer cells, and sometimes vice versa. Therefore, it is of particular interest to choose the right parameters such as starting time of external pressure, its magnitude and duration depending on the cell cycle of developing cancer cells. We propose a biologically inspired model that allows us to simulate the growth of cancer cells under conditions of osmotic pressure. We divide this growth into two phases. The first is characterized by active cell division, and the second by their growth. In this article, we introduce two types of pressure: short-term and long-term, and looked at what this leads to in different phases. We have found an interesting result, that there are some resonant points in time both in the first and second phases, when the introduction of additional pressure leads to the most significant slowdown in the growth of cancer cells.

Optical clearing of human skin: Molecular modeling and in vivo OCT study.

The results of in vivo immersion optical clearing of human skin under the action of two different optical clearing agents (OCAs), such as an aqueous sucrose solution and a radiographic contrast agent Omnipaque™ 300 (iohexol), were obtained with the use of optical coherence tomography (OCT) method. The rate of reduction of light scattering coefficient, obtained through an averaged A-scan of the OCT image in the region of dermis within the depths from 350 to 700 µm, were determined to evaluate the efficiency of optical clearing (EOC). The correlations between the EOC and the energy of intermolecular interaction of OCAs with a fragment of collagen peptide have been established as a result of molecular modeling by quantum chemistry methods HF/STO3G/DFT/B3LYP/6-311G(d) of a number of OCAs (glycerol, iohexol, sucrose, ribose, fructose, glucose) with mimetic peptide of collagen (GPH)3 .

Quantitative polarization-sensitive super-resolution solid immersion microscopy reveals biological tissues' birefringence in the terahertz range.

Terahertz (THz) technology offers a variety of applications in label-free medical diagnosis and therapy, majority of which rely on the effective medium theory that assumes biological tissues to be optically isotropic and homogeneous at the scale posed by the THz wavelengths. Meanwhile, most recent research discovered mesoscale ([Formula: see text]) heterogeneities of tissues; [Formula: see text] is a wavelength. This posed a problem of studying the related scattering and polarization effects of THz-wave-tissue interactions, while there is still a lack of appropriate tools and instruments for such studies. To address this challenge, in this paper, quantitative polarization-sensitive reflection-mode THz solid immersion (SI) microscope is developed, that comprises a silicon hemisphere-based SI lens, metal-wire-grid polarizer and analyzer, a continuous-wave 0.6 THz ([Formula: see text] µm) backward-wave oscillator (BWO), and a Golay detector. It makes possible the study of local polarization-dependent THz response of mesoscale tissue elements with the resolution as high as [Formula: see text]. It is applied to retrieve the refractive index distributions over the freshly-excised rat brain for the two orthogonal linear polarizations of the THz beam, aimed at uncovering the THz birefringence (structural optical anisotropy) of tissues. The most pronounced birefringence is observed for the Corpus callosum, formed by well-oriented and densely-packed axons bridging the cerebral hemispheres. The observed results are verified by the THz pulsed spectroscopy of the porcine brain, which confirms higher refractive index of the Corpus callosum when the THz beam is polarized along axons. Our findings highlight a potential of the quantitative polarization THz microscopy in biophotonics and medical imaging.

Terahertz dielectric spectroscopy and solid immersion microscopy of ex vivo glioma model 101.8: brain tissue heterogeneity.

Terahertz (THz) technology holds strong potential for the intraoperative label-free diagnosis of brain gliomas, aimed at ensuring their gross-total resection. Nevertheless, it is still far from clinical applications due to the limited knowledge about the THz-wave-brain tissue interactions. In this work, rat glioma model 101.8 was studied ex vivo using both the THz pulsed spectroscopy and the 0.15λ-resolution THz solid immersion microscopy (λ is a free-space wavelength). The considered homograft model mimics glioblastoma, possesses heterogeneous character, unclear margins, and microvascularity. Using the THz spectroscopy, effective THz optical properties of brain tissues were studied, as averaged within the diffraction-limited beam spot. Thus measured THz optical properties revealed a persistent difference between intact tissues and a tumor, along with fluctuations of the tissue response over the rat brain. The observed THz microscopic images showed heterogeneous character of brain tissues at the scale posed by the THz wavelengths, which is due to the distinct response of white and gray matters, the presence of different neurovascular structures, as well as due to the necrotic debris and hemorrhage in a tumor. Such heterogeneities might significantly complicate delineation of tumor margins during the intraoperative THz neurodiagnosis. The presented results for the first time pose the problem of studying the inhomogeneity of brain tissues that causes scattering of THz waves, as well as the urgent need to use the radiation transfer theory for describing the THz-wave - tissue interactions.

Terahertz dielectric spectroscopy of human brain gliomas and intact tissues ex vivo: double-Debye and double-overdamped-oscillator models of dielectric response.

Terahertz (THz) technology offers novel opportunities in the intraoperative neurodiagnosis. Recently, the significant progress was achieved in the study of brain gliomas and intact tissues, highlighting a potential for THz technology in the intraoperative delineation of tumor margins. However, a lack of physical models describing the THz dielectric permittivity of healthy and pathological brain tissues restrains the further progress in this field. In the present work, the ex vivo THz dielectric response of human brain tissues was analyzed using relaxation models of complex dielectric permittivity. Dielectric response of tissues was parametrized by a pair of the Debye relaxators and a pair of the overdamped-oscillators - namely, the double-Debye (DD) and double-overdamped-oscillator (DO) models. Both models accurately reproduce the experimental curves for the intact tissues and the WHO Grades I-IV gliomas. While the DD model is more common for THz biophotonics, the DO model is more physically rigorous, since it satisfies the sum rule. In this way, the DO model and the sum rule were, then, applied to estimate the content of water in intact tissues and gliomas ex vivo. The observed results agreed well with the earlier-reported data, justifying water as a main endogenous label of brain tumors in the THz range. The developed models can be used to describe completely the THz-wave - human brain tissues interactions in the frameworks of classical electrodynamics, being quite important for further research and developments in THz neurodiagnosis of tumors.

Capability of physically reasonable OCT-based differentiation between intact brain tissues, human brain gliomas of different WHO grades, and glioma model 101.8 from rats.

Optical coherence tomography (OCT) of the ex vivo rat and human brain tissue samples is performed. The set of samples comprises intact white and gray matter, as well as human brain gliomas of the World Health Organization (WHO) Grades I-IV and glioma model 101.8 from rats. Analysis of OCT signals is aimed at comparing the physically reasonable properties of tissues, and determining the attenuation coefficient, parameter related to effective refractive index, and their standard deviations. Data analysis is based on the linear discriminant analysis and estimation of their dispersion in a four-dimensional principal component space. The results demonstrate the distinct contrast between intact tissues and low-grade gliomas and moderate contrast between intact tissues and high-grade gliomas. Particularly, the mean values of attenuation coefficient are 7.56±0.91, 3.96±0.98, and 5.71±1.49 mm-1 for human white matter, glioma Grade I, and glioblastoma, respectively. The significant variability of optical properties of high Grades and essential differences between rat and human brain tissues are observed. The dispersion of properties enlarges with increase of the glioma WHO Grade, which can be attributed to the growing heterogeneity of pathological brain tissues. The results of this study reveal the advantages and drawbacks of OCT for the intraoperative diagnosis of brain gliomas and compare its abilities separately for different grades of malignancy. The perspective of OCT to differentiate low-grade gliomas is highlighted by the low performance of the existing intraoperational methods and instruments.

Multimodal Optical Diagnostics of Glycated Biological Tissues.

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia accompanied by the disruption of carbohydrate, lipid, and proteins metabolism and development of long-term microvascular, macrovascular, and neuropathic changes. This review presents the results of spectroscopic studies on the glycation of tissues and cell proteins in organisms with naturally developing and model diabetes and in vitro glycated samples in a wide range of electromagnetic waves, from visible light to terahertz radiation. Experiments on the refractometric measurements of glycated and oxygenated hemoglobin in broad wavelength and temperature ranges using digital holographic microscopy and diffraction tomography are discussed, as well as possible application of these methods in the diabetes diagnostics. It is shown that the development and implementation of multimodal approaches based on a combination of phase diagnostics with other methods is another promising direction in the diabetes diagnostics. The possibilities of using optical clearing agents for monitoring the diffusion of substances in the glycated tissues and blood flow dynamics in the pancreas of animals with induced diabetes have also been analyzed.

Methods for Optical Skin Clearing in Molecular Optical Imaging in Dermatology.

This short review describes recent progress in using optical clearing (OC) technique in skin studies. Optical clearing is an efficient tool for enhancing the probing depth and data quality in multiphoton microscopy and Raman spectroscopy. Here, we discuss the main mechanisms of OC, its safety, advantages, and limitations. The data on the OC effect on the skin water content are presented. It was demonstrated that 70% glycerol and 100% OmnipaqueTM 300 reduce the water content in the skin. Both OC agents (OCAs) significantly affect the strongly bound and weakly bound water. However, OmnipaqueTM 300 causes considerably less skin dehydration than glycerol. In addition, the results of examination of the OC effect on autofluorescence in two-photon excitation and background fluorescence in Raman scattering at different skin depths are presented. It is shown that OmnipaqueTM 300 is a promising OCA due to its ability to reduce background fluorescence in the upper skin layers. The possibility of multimodal imaging combining optical methods and OC technique is discussed.

Glycerol dehydration of native and diabetic animal tissues studied by THz-TDS and NMR methods.

The optical clearing method has been widely used for different spectral ranges where it provides tissue transparency. In this work, we observed the enhanced penetration of the terahertz waves inside biological samples (skin, kidney, and cornea) treated with glycerol solutions inducing changes of optical and dielectric properties. It was supported by the observed trend of free-to-bound water ratio measured by the nuclear magnetic resonance (NMR) method. The terahertz clearing efficiency was found to be less for diabetic samples than for normal ones. Results of the numerical simulation proved that pulse deformation is due to bigger penetration depth caused by the reduction of absorption and refraction at optical clearing.

Recent progress in tissue optical clearing for spectroscopic application.

This paper aims to review recent progress in optical clearing of the skin and over naturally turbid biological tissues and blood using this technique in vivo and in vitro with multiphoton microscopy, confocal Raman microscopy, confocal microscopy, NIR spectroscopy, optical coherence tomography, and laser speckle contrast imaging. Basic principles of the technique, its safety, advantages and limitations are discussed. The application of optical clearing agent on a tissue allows for controlling the optical properties of tissue. Optical clearing-induced reduction of tissue scattering significantly facilitates the observation of deep-located tissue regions, at the same time improving the resolution and image contrast for a variety of optical imaging methods suitable for clinical applications, such as diagnostics and laser treatment of skin diseases, mucosal tumor imaging, laser disruption of pathological abnormalities, etc.

Multiresolution analysis of pathological changes in cerebral venous dynamics in newborn mice with intracranial hemorrhage: adrenorelated vasorelaxation.

Intracranial hemorrhage (ICH) is the major problem of modern neonatal intensive care. Abnormalities of cerebral venous blood flow (CVBF) can play a crucial role in the development of ICH in infants. The mechanisms underlying these pathological processes remain unclear; however it has been established that the activation of the adrenorelated vasorelaxation can be an important reason. Aiming to reach a better understanding of how the adrenodependent relaxation of cerebral veins contributes to the development of ICH in newborns, we study here the effects of pharmacological stimulation of adrenorelated dilation of the sagittal sinus by isoproterenol on the cerebral venous hemodynamics. Our study is performed in newborn mice at different stages of ICH using the laser speckle contrast imaging and wavelet analysis of the vascular dynamics of CVBF. We show that the dilation of the sagittal sinus with the decreased velocity of blood flow presides to the stress-induced ICH in newborn mice. These morphofunctional vascular changes are accompanied by an increased variance of the wavelet-coefficients in the areas of endothelial and non-endothelial (KATP-channels activity of vascular muscle) sympathetic components of the CVBF variability. Changes in the cerebral venous hemodynamics at the latent stage of ICH are associated with a high responsiveness of the sagittal sinus to isoproterenol quantifying by wavelet-coefficients related to a very slow region of the frequency domain. The obtained results certify that a high activation of the adrenergic-related vasodilatory responses to severe stress in newborn mice can be one of the important mechanisms underlying the development of ICH. Thus, the venous insufficiency with the decreased blood outflow from the brain associated with changes in the endothelial and the sympathetic components of CVBF-variability can be treated as prognostic criteria for the risk of ICH during the first days after birth.

[Kinetics of changes in the coefficient of transmission of the adipose tissue in vitro as a result of photodynamic action].

Changes in the light transmission coefficient of human adipose cells as a result of photodynamic action have been detected and investigated. Based on the statistical processing of digital micrographs of thin tissue slices, the kinetics of processes occurring in the adipose tissue has been quantitatively estimated. It has been suggested that the effects observed are brought about through the lipolysis of adipose cells with the retention of their structure.

[Photodynamic effect on cells of human adipose tissue in vitro].

Changes in optical properties of human adipose tissue cells after photodynamic exposure in vitro were found and investigated. Analysis of the kinetics of the process was realized by means of photomicrography of the object investigated. The statistical computer processing of digital photos obtained gave us an opportunity to estimate quantitatively the kinetics of photodynamic effect upon the tissue. Optical interpretation of the photos obtained indicates that the observed phenomenon corresponds to the partial lysis of adipose tissue cells without their complete destruction.

[Plasma dehydratation self-organization in patients with coronary heart].

The functional morphology of biological fluids is a basically new branch of science, which is based on the study of a result of phase change processes in the substrate under study. The paper shows the specific features of plasma spatial organization in patients with chronic and acute coronary heart disease (CHD). The findings may be used as an additional criterion for the differential diagnosis of the above forms of CHD and open up a new line in the diagnosis and risk stratification in CHD patients.

[Role of the carbohydrate-binding center of bacterial lectin in the effect on adipocytes under the influence of increased temperature].

The effect of temperature and lectin from bacteria of the genues Azospirillum with blocked activity on human adipose tissue cells has been studied. The temperature used was 43.5 +/- 0.5 degrees C. Comparative results are given for the effect of lectin with the blocked and active carbohydrate-binding centers on adipocytes during heating, and the time course of the structural changes of adipocytes is described. When lectin with the active carbohydrate-binding centers was used for treatment, the heat-treated cells of a healthy obesity-prone subject died on the average in 55 +/- 5 min, whereas cells treated with lectin with the L-fucose-blocked carbohydrate-binding centers died in 80 +/- 5 min. The heat-treated cells of a diabetic obesity-prone patient died in 150 +/- 10 min on average when exposed to both active and inactive lectin. Consequently, when the lectin center is blocked with L-fucose, the effectiveness of lectin action on adipose cells of healthy obesity-prone persons decreases.

Optical monitoring of microlymphatic disturbances during experimental lymphedema.

BACKGROUND: Rat mesentery has been widely used to study microvascular functions. The goal of this work is to extend this animal model to monitor blood and lymph microvessel function during lymphedema. METHODS AND RESULTS: Lymphedema is created by microsurgical removal of regional lymph nodes (lymphadenectomy) or ligation of the collecting vein. Water volume in mesenteric tissue, microvessel diameters, phasic contraction, valve function, lymph flow velocity, and cell migration were analyzed during lymphedema development. Dynamic observation of water amount after lymphadenectomy revealed increasing edema from 30 min to 1 week; greatest degree of edema at one week, and gradual decrease in edema from 1 to 11 weeks. These effects were accompanied by acute constriction of lymph vessels and slowing of lymph flow velocity, switching to dilation and appearance of new blood capillaries at week 1, progressing to dilation and degenerative changes of the microlymphatic wall at week 4, and, finally, leading to lymphatic fibrosis and lymphangiogenesis at week 11. Acute venous insufficiency (30 min after vein ligation) led to significant edema, decreasing blood flow velocity to stasis, and output of erythrocytes from venules to interstitium, with further movement to microlymphatics and regional lymph nodes. CONCLUSIONS: Rat mesentery as an animal model in combination with an advanced optical imaging system is valuable in studying microlymphatic disturbances in mesentery during the development of experimental lymphedema from latent period to chronic stages, including monitoring of individual cell dislocation with high resolution optical imaging.

[Diffusion of methylene blue in the human maxillary sinus mucosa].

The coefficient of diffusion of methylene blue in pathologically changed human maxillary sinus mucosa in vitro has been estimated for the first time. The mean value of the diffusion coefficient is (4.8 +/- 2.9) x 10(-7) cm2/s. The method is based on the registration of the dynamics of reflectance of tissue samples under the action of the dye. The diffusion coefficient has been estimated by approximation of experimental data in the framework of the model presented.