Real-time laser speckle contrast imaging for intraoperative neurovascular blood flow assessment: animal experimental study.

The use of various blood flow control methods in neurovascular interventions is crucial for reducing postoperative complications. Neurosurgeons worldwide use different methods, such as contact Dopplerography, intraoperative indocyanine videoangiography (ICG) video angiography, fluorescein angiography, flowmetry, intraoperative angiography, and direct angiography. However, there is no noninvasive method that can assess the presence of blood flow in the vessels of the brain without the introduction of fluorescent substances throughout the intervention. The real-time laser-speckle contrast imaging (LSCI) method was studied for its effectiveness in controlling blood flow in standard cerebrovascular surgery cases in rat common carotid arteries, such as proximal occlusion, trapping, reperfusion, anastomosis, and intraoperative vessel thrombosis. The real-time LSCI method is a promising method for use in neurosurgical practice. This approach allows timely diagnosis of intraoperative disturbance of blood flow in vessels in cases of clip occlusion or thrombosis. Additionally, LSCI allows us to reliably confirm the functioning of the anastomosis and reperfusion after removal of the clips and thrombolysis in real time. An unresolved limitation of the method is noise from movements, but this does not reduce the value of the method. Additional research is required to improve the quality of the data obtained.

Incremental residual polarization caused by aging in human skin.

Significance: The study of the effect of aging on the optical properties of biological tissues, in particular polarization, is important in the development of new diagnostic approaches. Aim: This work aims to provide a comprehensive analysis of the factors and mechanisms that contribute to the alteration of skin polarization properties caused by aging, using polarization-sensitive hyperspectral imaging measurements and Monte Carlo simulation. Approach: Our investigation involved both experimental studies of in vivo human skin of volunteers of different ages and computational modeling that accounted for changes in the absorption and scattering properties of the skin model. Specifically, we analyzed alterations in the degree of linear polarization (DOLP) to better understand the impact of aging on skin polarization properties. Results: A statistically significant increase in the DOLP was found for the elderly group. At the same time, there was no correlation between changes in polarization and the calculated blood volume fraction parameter for different ages. According to the simulation results, it was also found that a change in the scattering properties of biological tissues has a more significant effect on the change in polarizing light compared to the change in absorption. Conclusions: The results of the work prove that the sensitivity of polarization imaging to age- or pathological-related skin changes may be primarily due to changes in scattering, which in turn is associated with changes in the collagen fibers of the dermis. The proposed technique shows promise for in vivo non-invasive real-time assessment of age-associated skin changes and can also be extended to monitor changes associated with the development of age-related pathologies.

Exploring the evolution of circular polarized light backscattered from turbid tissue-like disperse medium utilizing generalized Monte Carlo modeling approach with a combined use of Jones and Stokes-Mueller formalisms.

Significance: Phase retardation of circularly polarized light (CPL), backscattered by biological tissue, is used extensively for quantitative evaluation of cervical intraepithelial neoplasia, presence of senile Alzheimer's plaques, and characterization of biotissues with optical anisotropy. The Stokes polarimetry and Mueller matrix approaches demonstrate high potential in definitive non-invasive cancer diagnosis and tissue characterization. The ultimate understanding of CPL interaction with tissues is essential for advancing medical diagnostics, optical imaging, therapeutic applications, and the development of optical instruments and devices. Aim: We investigate propagation of CPL within turbid tissue-like scattering medium utilizing a combination of Jones and Stokes-Mueller formalisms in a Monte Carlo (MC) modeling approach. We explore the fundamentals of CPL memory effect and depolarization formation. Approach: The generalized MC computational approach developed for polarization tracking within turbid tissue-like scattering medium is based on the iterative solution of the Bethe-Salpeter equation. The approach handles helicity response of CPL scattered in turbid medium and provides explicit expressions for assessment of its polarization state. Results: Evolution of CPL backscattered by tissue-like medium at different conditions of observation in terms of source-detector configuration is assessed quantitatively. The depolarization of light is presented in terms of the coherence matrix and Stokes-Mueller formalism. The obtained results reveal the origins of the helicity flip of CPL depending on the source-detector configuration and the properties of the medium and are in a good agreement with the experiment. Conclusions: By integrating Jones and Stokes-Mueller formalisms, the combined MC approach allows for a more complete representation of polarization effects in complex optical systems. The developed model is suitable to imitate propagation of the light beams of different shape and profile, including Gaussian, Bessel, Hermite-Gaussian, and Laguerre-Gaussian beams, within tissue-like medium. Diverse configuration of the experimental conditions, coherent properties of light, and peculiarities of polarization can be also taken into account.

Multiplexed spatially-focused localization of light in adipose biological tissues.

Last decades the effects of localization and focusing of light in turbid randomly inhomogeneous tissue-like scattering medium have been attracting a particular attention. Weak localization of light in disordered and weakly ordered biological tissue, polarization memory effect, correlations in transmission matrices, focusing light by wavefronts shaping have been widely exploited. Here, we represent an experimentally observed and theoretically confirmed new type of spatial localization of light within biological tissues. General description of the observed phenomenon based on Monte Carlo ray tracing model is provided. We find that innate body arrangements of individual adipocytes can act as a cascade of quasi-ordered microscale lenses confining propagation of light within adipose tissues similar to lens lightguides. The observed spatially-resolved longitudinal multi-focusing of light within disordered adipose biological tissues can naturally lead greater spatial control and enhance light-tissue interactions.

Influence of blood pulsation on diagnostic volume in pulse oximetry and photoplethysmography measurements.

Recent advances in the development of ultra-compact semiconductor lasers and technology of printed flexible hybrid electronics have opened broad perspectives for the design of new pulse oximetry and photoplethysmography devices. Conceptual design of optical diagnostic devices requires careful selection of various technical parameters, including spectral range; polarization and intensity of incident light; actual size, geometry, and sensitivity of the detector; and mutual position of the source and detector on the surface of skin. In the current study utilizing a unified Monte Carlo computational tool, we explore the variations in diagnostic volume due to arterial blood pulsation for typical transmitted and back-scattered probing configurations in a human finger. The results of computational studies show that the variations in diagnostic volumes due to arterial pulse wave are notably (up to 45%) different in visible and near-infrared spectral ranges in both transmitted and back-scattered probing geometries. While these variations are acceptable for relative measurements in pulse oximetry and/or photoplethysmography, for absolute measurements, an alignment normalization of diagnostic volume is required and can be done by a computational approach utilized in the framework of the current study.

Mueller-matrix-based polarization imaging and quantitative assessment of optically anisotropic polycrystalline networks.

We introduce a Mueller-matrix imaging polarization-based approach for the quantitative digital screening of the polycrystalline structure of fibrillary-based biological tissues in vitro. The morphometric evaluation of histological sections of myocardium was performed utilizing the high-order statistical moments calculated based on the spatial distribution of linear and circular birefringence and dichroism obtained experimentally. We demonstrate that spatial distributions of phase of light and optical anisotropy of scattering inherent to fibrillar networks of myocardium at different necrotic stages can be effectively used as a quantitative marker of stages of myosin fibril degradation. Processing the images of phase of light scattered in biological tissues with high order statistical analysis provides a functional tool for the quantitative characterization of necrotic conditions of the myocardium.

Terahertz time-domain spectroscopy for non-invasive assessment of water content in biological samples.

We apply terahertz time-domain spectroscopy for the quantitative non-invasive assessment of the water content in biological samples, such as Carpinus caroliniana tree leaves and pork muscles. The developed experimental terahertz time-domain spectroscopy system operates both in transmission and reflection modes. The Landau-Looyenga-Lifshitz-based model is used for the calculation of the water concentration within the samples. The results of the water concentration measurements are compared with the results of the gravimetric measurements. The obtained results show that the water content in biological samples can be measured non-invasively, with a high accuracy, utilizing terahertz waves in transmission and reflection modes.

Assessment of the dynamics of human glymphatic system by near-infrared spectroscopy.

Fluctuations in brain water content has attracted increasing interest, particularly as regards studies of the glymphatic system, which is connected with the complex organization of dural lymphatic vessels, responsible for cleaning tissue. Disturbances of glymphatic circulation are associated with several brain disorders, including dementia. This article introduces an approach to noninvasive measurement of water dynamics in the human brain utilizing near-infrared spectroscopy (NIRS). We demonstrate the possibility to sense dynamic variations of water content between the skull and grey matter, for instance, in the subarachnoid space. Measured fluctuations in water content, especially in the cerebrospinal fluid (CSF), are assumed to be correlated with the dynamics of glymphatic circulation. The sampling volume for the NIRS optode was estimated by Monte Carlo modelling for the wavelengths of 660, 740, 830 and 980 nm. In addition, using combinations of these wavelengths, this article presents the calculation models for quantifying water and haemodynamics. The presented NIRS technique allows long-term functional brain monitoring, including sleeping time. Furthermore, it is used in combination with different magnetic neuroimaging techniques, particularly magnetic resonance encephalography. Using the combined setup, we report the preliminary results on the interaction between CSF and blood oxygen level-dependent fluctuations.

Influence of probe pressure on diffuse reflectance spectra of human skin measured in vivo.

Mechanical pressure superficially applied on the human skin surface by a fiber-optic probe influences the spatial distribution of blood within the cutaneous tissues. Upon gradual load of weight on the probe, a stepwise increase in the skin reflectance spectra is observed. The decrease in the load follows the similar inverse staircase-like tendency. The observed stepwise reflectance spectra changes are due to, respectively, sequential extrusion of blood from the topical cutaneous vascular beds and their filling afterward. The obtained results are confirmed by Monte Carlo modeling. This implies that pressure-induced influence during the human skin diffuse reflectance spectra measurements in vivo should be taken into consideration, in particular, in the rapidly developing area of wearable gadgets for real-time monitoring of various human body parameters.

Remote in vivo stress assessment of aquatic animals with microencapsulated biomarkers for environmental monitoring.

Remote in vivo scanning of physiological parameters is a major trend in the development of new tools for the fields of medicine and animal physiology. For this purpose, a variety of implantable optical micro- and nanosensors have been designed for potential medical applications. At the same time, the important area of environmental sciences has been neglected in the development of techniques for remote physiological measurements. In the field of environmental monitoring and related research, there is a constant demand for new effective and quick techniques for the stress assessment of aquatic animals, and the development of proper methods for remote physiological measurements in vivo may significantly increase the precision and throughput of analyses in this field. In the present study, we apply pH-sensitive microencapsulated biomarkers to remotely monitor the pH of haemolymph in vivo in endemic amphipods from Lake Baikal, and we compare the suitability of this technique for stress assessment with that of common biochemical methods. For the first time, we demonstrate the possibility of remotely detecting a change in a physiological parameter in an aquatic organism under ecologically relevant stressful conditions and show the applicability of techniques using microencapsulated biomarkers for remote physiological measurements in environmental monitoring.

Backscattering of linearly polarized light from turbid tissue-like scattering medium with rough surface.

In the framework of further development of a unified computational tool for the needs of biomedical optics, we introduce an electric field Monte Carlo (MC) model for simulation of backscattering of coherent linearly polarized light from a turbid tissue-like scattering medium with a rough surface. We consider the laser speckle patterns formation and the role of surface roughness in the depolarization of linearly polarized light backscattered from the medium. The mutual phase shifts due to the photons' pathlength difference within the medium and due to reflection/refraction on the rough surface of the medium are taken into account. The validation of the model includes the creation of the phantoms of various roughness and optical properties, measurements of co- and cross-polarized components of the backscattered/reflected light, its analysis and extensive computer modeling accelerated by parallel computing on the NVIDIA graphics processing units using compute unified device architecture (CUDA). The analysis of the spatial intensity distribution is based on second-order statistics that shows a strong correlation with the surface roughness, both with the results of modeling and experiment. The results of modeling show a good agreement with the results of experimental measurements on phantoms mimicking human skin. The developed MC approach can be used for the direct simulation of light scattered by the turbid scattering medium with various roughness of the surface.

Two electric field Monte Carlo models of coherent backscattering of polarized light.

Modeling of coherent polarized light propagation in turbid scattering medium by the Monte Carlo method provides an ultimate understanding of coherent effects of multiple scattering, such as enhancement of coherent backscattering and peculiarities of laser speckle formation in dynamic light scattering (DLS) and optical coherence tomography (OCT) diagnostic modalities. In this report, we consider two major ways of modeling the coherent polarized light propagation in scattering tissue-like turbid media. The first approach is based on tracking transformations of the electric field along the ray propagation. The second one is developed in analogy to the iterative procedure of the solution of the Bethe-Salpeter equation. To achieve a higher accuracy in the results and to speed up the modeling, both codes utilize the implementation of parallel computing on NVIDIA Graphics Processing Units (GPUs) with Compute Unified Device Architecture (CUDA). We compare these two approaches through simulations of the enhancement of coherent backscattering of polarized light and evaluate the accuracy of each technique with the results of a known analytical solution. The advantages and disadvantages of each computational approach and their further developments are discussed. Both codes are available online and are ready for immediate use or download.

Propagation of coherent polarized light in turbid highly scattering medium.

Within the framework of further development of unified Monte Carlo code for the needs of biomedical optics and biophotonics, we present an approach for modeling of coherent polarized light propagation in highly scattering turbid media, such as biological tissues. The temporal coherence of light, linear and circular polarization, interference, and the helicity flip of circularly polarized light due to reflection at the medium boundary and/or backscattering events are taken into account. To achieve higher accuracy in the results and to speed up the modeling, the implementation of the code utilizes parallel computing on NVIDIA graphics processing units using Compute Unified Device Architecture. The results of the simulation of coherent linearly and circularly polarized light are presented in comparison with the results of known theoretical studies and the results of alternative modelings.

Evaluation of path-history-based fluorescence Monte Carlo method for photon migration in heterogeneous media.

The path-history-based fluorescence Monte Carlo method used for fluorescence tomography imaging reconstruction has attracted increasing attention. In this paper, we first validate the standard fluorescence Monte Carlo (sfMC) method by experimenting with a cylindrical phantom. Then, we describe a path-history-based decoupled fluorescence Monte Carlo (dfMC) method, analyze different perturbation fluorescence Monte Carlo (pfMC) methods, and compare the calculation accuracy and computational efficiency of the dfMC and pfMC methods using the sfMC method as a reference. The results show that the dfMC method is more accurate and efficient than the pfMC method in heterogeneous medium.

Peer-to-peer Monte Carlo simulation of photon migration in topical applications of biomedical optics.

In the framework of further development of the unified approach of photon migration in complex turbid media, such as biological tissues we present a peer-to-peer (P2P) Monte Carlo (MC) code. The object-oriented programming is used for generalization of MC model for multipurpose use in various applications of biomedical optics. The online user interface providing multiuser access is developed using modern web technologies, such as Microsoft Silverlight, ASP.NET. The emerging P2P network utilizing computers with different types of compute unified device architecture-capable graphics processing units (GPUs) is applied for acceleration and to overcome the limitations, imposed by multiuser access in the online MC computational tool. The developed P2P MC was validated by comparing the results of simulation of diffuse reflectance and fluence rate distribution for semi-infinite scattering medium with known analytical results, results of adding-doubling method, and with other GPU-based MC techniques developed in the past. The best speedup of processing multiuser requests in a range of 4 to 35 s was achieved using single-precision computing, and the double-precision computing for floating-point arithmetic operations provides higher accuracy.

Online object oriented Monte Carlo computational tool for the needs of biomedical optics.

Conceptual engineering design and optimization of laser-based imaging techniques and optical diagnostic systems used in the field of biomedical optics requires a clear understanding of the light-tissue interaction and peculiarities of localization of the detected optical radiation within the medium. The description of photon migration within the turbid tissue-like media is based on the concept of radiative transfer that forms a basis of Monte Carlo (MC) modeling. An opportunity of direct simulation of influence of structural variations of biological tissues on the probing light makes MC a primary tool for biomedical optics and optical engineering. Due to the diversity of optical modalities utilizing different properties of light and mechanisms of light-tissue interactions a new MC code is typically required to be developed for the particular diagnostic application. In current paper introducing an object oriented concept of MC modeling and utilizing modern web applications we present the generalized online computational tool suitable for the major applications in biophotonics. The computation is supported by NVIDEA CUDA Graphics Processing Unit providing acceleration of modeling up to 340 times.

Simulation of optical coherence tomography images by Monte Carlo modeling based on polarization vector approach.

Monte Carlo method is applied for simulation of 2D optical coherence tomography (OCT) images of skin-like model. Layer boundaries in skin model feature curved shape which agrees with physiological structure of human skin. The effect of coherence properties of probing radiation on OCT image formation and speckles in the detected OCT signal is considered. The developed model is employed for image simulation both for conventional and polarization dependent time-domain OCT modalities. Simulation of polarized OCT signal is performed using vector approach developed previously for modeling of electromagnetic field transfer in turbid media.

Laser light scattering in turbid media Part II: Spatial and temporal analysis of individual scattering orders via Monte Carlo simulation.

In Part I of this study [1], good agreement between experimental measurements and results from Monte Carlo simulations were obtained for the spatial intensity distribution of a laser beam propagating within a turbid environment. In this second part, the validated Monte Carlo model is used to investigate spatial and temporal effects from distinct scattering orders on image formation. The contribution of ballistic photons and the first twelve scattering orders are analyzed individually by filtering the appropriate data from simulation results. Side-scattering and forward-scattering detection geometries are investigated and compared. We demonstrate that the distribution of positions for the final scattering events is independent of particle concentration when considering a given scattering order in forward detection. From this observation, it follows that the normalized intensity distribution of each order, in both space and time, is independent of the number density of particles. As a result, the amount of transmitted information is constant for a given scattering order and is directly related to the phase function in association with the detection acceptance angle. Finally, a contrast analysis is performed in order to quantify this information at the image plane.

Simulation of polarization-sensitive optical coherence tomography images by a Monte Carlo method.

We introduce a new Monte Carlo (MC) method for simulating optical coherence tomography (OCT) images of complex multilayered turbid scattering media. We demonstrate, for the first time of our knowledge, the use of a MC technique to imitate two-dimensional polarization-sensitive OCT images with nonplanar boundaries of layers in the medium like a human skin. The simulation of polarized low-coherent optical radiation is based on the vector approach generalized from the iterative procedure of the solution of Bethe-Saltpeter equation. The performances of the developed method are demonstrated both for conventional and polarization-sensitive OCT modalities.

Crossed source-detector geometry for a novel spray diagnostic: Monte Carlo simulation and analytical results.

Sprays and other industrially relevant turbid media can be quantitatively characterized by light scattering. However, current optical diagnostic techniques generate errors in the intermediate scattering regime where the average number of light scattering is too great for the single scattering to be assumed, but too few for the diffusion approximation to be applied. Within this transitional single-to-multiple scattering regime, we consider a novel crossed source-detector geometry that allows the intensity of single scattering to be measured separately from the higher scattering orders. We verify Monte Carlo calculations that include the imperfections of the experiment against analytical results. We show quantitatively the influence of the detector numerical aperture and the angle between the source and the detector on the relative intensity of the scattering orders in the intermediate single-to-multiple scattering regime. Monte Carlo and analytical calculations of double light-scattering intensity are made with small particles that exhibit isotropic scattering. The agreement between Monte Carlo and analytical techniques validates use of the Monte Carlo approach in the intermediate scattering regime. Monte Carlo calculations are then performed for typical parameters of sprays and aerosols with anisotropic (Mie) scattering in the intermediate single-to-multiple scattering regime.