Photon-cell interactive Monte Carlo model based on the geometric optics theory for photon migration in blood by incorporating both extra- and intracellular pathways

A photon-cell interactive Monte Carlo (pciMC) that tracks photon migration in both the extra- and intracellular spaces is developed without using macroscopic scattering phase functions and anisotropy factors, as required for the conventional Monte Carlos (MCs). The interaction of photons at the plasma-cell boundary of randomly oriented 3-D biconcave red blood cells (RBCs) is modeled using the geometric optics. The pciMC incorporates different photon velocities from the extra- to intracellular space, whereas the conventional MC treats RBCs as points in the space with a constant velocity. In comparison to the experiments, the pciMC yielded the mean errors in photon migration time of 9.8±6.8 and 11.2±8.5% for suspensions of small and large RBCs (RBC(small), RBC(large)) averaged over the optically diffusing region from 2000 to 4000 μm, while the conventional random walk Monte Carlo simulation gave statistically higher mean errors of 19.0±5.8 (?p?相似文献   

Multiple scattering effects in Doppler optical coherence tomography of flowing blood

We investigate the effect of multiple scattering on the optical coherence tomography (OCT) signal and the Doppler OCT signal of flowing blood. Doppler OCT measurements at 1300 nm are performed on flowing diluted porcine blood with hematocrit ranging between 0% and 15%. Measured blood hematocrit and mean red blood cell volume are used to calculate, using the discrete dipole approximation model, the (single) scattering coefficient and scattering anisotropy of blood. Monte Carlo simulations, based on the calculated scattering coefficients and scattering anisotropies, are compared to Doppler OCT measurements for hematocrit smaller than 10%. Good quantitative agreement between Doppler OCT measurements and Monte Carlo simulations is observed. Our measurements, calculations and simulations explain the relatively low attenuation coefficients and well preserved flow profiles measured with Doppler OCT for flowing blood. Monte Carlo simulations demonstrate the effect of the scattering anisotropy of the medium on the strength of multiple scattering effects in Doppler OCT signals. With increasing scattering anisotropy the OCT attenuation decreases; the distortion of the flow profile is strongest at intermediate scattering anisotropies (≈0.6).     

Toward a velocity-resolved microvascular blood flow measure by decomposition of the laser Doppler spectrum

Tissue microcirculation, as measured by laser Doppler flowmetry (LDF), comprises capillary, arterial, and venous blood flow. With the classical LDF approach, it has been impossible to differentiate between different vascular compartments. We suggest an alternative LDF algorithm that estimates at least three concentration measures of flowing red blood cells (RBCs), each associated with a predefined, physiologically relevant, absolute velocity in millimeters per second. As the RBC flow velocity depends on the dimension of the blood vessel, this approach might enable a microcirculatory flow differentiation. The LDF concentration estimates are derived by fitting predefined Monte Carlo simulated, single-velocity spectra to a measured, multiple-velocity LDF spectrum. Validation measurements, using both single- and double-tube flow phantoms perfused with a microsphere solution, show that it is possible to estimate velocity and concentration changes, and to differentiate between flows with different velocities. Our theory is also applied to RBC flow measurements. A Gegenbauer kernel phase function (alpha(gk)=1.05; g(gk)=0.93), with an anisotropy factor of 0.987 at 786 nm, is found suitable for modeling Doppler scattering by RBCs diluted in physiological saline. The method is developed for low concentrations of RBCs, but can in theory be extended to cover multiple Doppler scattering.     

Anisotropic light scattering of individual sickle red blood cells

We present the anisotropic light scattering of individual red blood cells (RBCs) from a patient with sickle cell disease (SCD). To measure light scattering spectra along two independent axes of elongated-shaped sickle RBCs with arbitrary orientation, we introduce the anisotropic Fourier transform light scattering (aFTLS) technique and measured both the static and dynamic anisotropic light scattering. We observed strong anisotropy in light scattering patterns of elongated-shaped sickle RBCs along its major axes using static aFTLS. Dynamic aFTLS analysis reveals the significantly altered biophysical properties in individual sickle RBCs. These results provide evidence that effective viscosity and elasticity of sickle RBCs are significantly different from those of the healthy RBCs.     

Light scattering of human red blood cells during metabolic remodeling of the membrane

We present the light scattering properties of individual human red blood cells (RBCs). We show that both the RBC static and dynamic scattering signals are altered by adenosine 5'-triphosphate (ATP)-driven membrane metabolic remodeling. To measure the light scattering signal from individual RBCs, we use diffraction phase microscopy together with a Fourier transform light scattering technique. RBC cytosolic ATPs are both chemically and metabolically depleted, and the corresponding scattering signals are compared with the light scattering signal of normal RBCs having physiologic levels of ATP.     

Polarized light propagation in multiply scattering media exhibiting both linear birefringence and optical activity: Monte Carlo model and experimental methodology

A Monte Carlo model for polarized light propagation in birefringent, optically active, multiply scattering media is developed in an effort to accurately represent the propagation of polarized light in biological tissue. The model employs the Jones N-matrix formalism to combine both linear birefringence and optical activity into a single effect that can be applied to photons as they propagate between scattering events. Polyacrylamide phantoms with strain-induced birefringence, sucrose-induced optical activity, and polystyrene microspheres as scattering particles are used for experimental validation. Measurements are made using a Stokes polarimeter that detects scattered light in different geometries, and compared to the results of Monte Carlo simulations run with similar parameters. The results show close agreement between the experimental measurements and Monte Carlo calculations for phantoms exhibiting turbidity and birefringence, as well as for phantoms exhibiting turbidity, birefringence, and optical activity. Other scattering-independent polarization properties can be incorporated into the developed Jones N-matrix formalism, enabling quantification of the polarization effects via an accurate polarization-sensitive Monte Carlo model.     

Determination of the optical properties of anisotropic biological media using an isotropic diffusion model

We investigate anisotropic light propagation in biological tissue in steady-state and time domains. Monte Carlo simulations performed for tissue that consists of aligned cylindrical and spherical scatterers show that steady-state and time-resolved reflectance depends strongly on the measurement direction relative to the alignment of the cylinder axis. We examine the determination of optical properties using an isotropic diffusion model and find that in the time domain, in contrast to steady-state spatially resolved reflectance measurements, the obtained absorption coefficient does not depend on the measurement direction and is close to the true value. Contrarily, the derived reduced scattering coefficient depends strongly on the measurement direction in both domains. Measurements of the steady-state and time-resolved reflectance from bovine tendon confirm the theoretical findings.     

红细胞非惯性升力对血液流动的影响

目的 为准确模拟血流,研究红细胞变形性对血液流动的影响。方法 基于血液流变特性和红细胞力学特性分析,对现有血液两相流流动模型进行改进,改进模型中考虑了易变形红细胞受剪切流场或血管壁面作用而产生的非惯性升力的影响。利用改进模型对多个不同直径血管内的血液流动进行模拟。结果 由红细胞所受非惯性升力导致的径向运动对血管内红细胞体积分数、运动速度分布有明显影响;当血管直径为0.1~3.0 mm时,用改进模型得到的血液相对黏度的模拟值与测量值接近。结论 非惯性升力是血流呈现Fahraeus-Lindqvist效应的主要原因之一。考虑非惯性升力的改进模型可以准确模拟血液流动,为循环系统诊疗机制和细胞分选等过程的模拟提供更为准确的方法。     

红细胞非惯性升力对血液流动的影响

目的为准确模拟血流,研究红细胞变形性对血液流动的影响。方法基于血液流变特性和红细胞力学特性分析,对现有血液两相流流动模型进行改进,改进模型中考虑了易变形红细胞受剪切流场或血管壁面作用而产生的非惯性升力的影响。利用改进模型对多个不同直径血管内的血液流动进行模拟。结果由红细胞所受非惯性升力导致的径向运动对血管内红细胞体积分数、运动速度分布有明显影响;当血管直径为0.1~3.0 mm时,用改进模型得到的血液相对黏度的模拟值与测量值接近。结论非惯性升力是血流呈现Fahraeus-Lindqvist效应的主要原因之一。考虑非惯性升力的改进模型可以准确模拟血液流动,为循环系统诊疗机制和细胞分选等过程的模拟提供更为准确的方法。     

Inverse Monte Carlo method in a multilayered tissue model for diffuse reflectance spectroscopy

Model based data analysis of diffuse reflectance spectroscopy data enables the estimation of optical and structural tissue parameters. The aim of this study was to present an inverse Monte Carlo method based on spectra from two source-detector distances (0.4 and 1.2 mm), using a multilayered tissue model. The tissue model variables include geometrical properties, light scattering properties, tissue chromophores such as melanin and hemoglobin, oxygen saturation and average vessel diameter. The method utilizes a small set of presimulated Monte Carlo data for combinations of different levels of epidermal thickness and tissue scattering. The path length distributions in the different layers are stored and the effect of the other parameters is added in the post-processing. The accuracy of the method was evaluated using Monte Carlo simulations of tissue-like models containing discrete blood vessels, evaluating blood tissue fraction and oxygenation. It was also compared to a homogeneous model. The multilayer model performed better than the homogeneous model and all tissue parameters significantly improved spectral fitting. Recorded in vivo spectra were fitted well at both distances, which we previously found was not possible with a homogeneous model. No absolute intensity calibration is needed and the algorithm is fast enough for real-time processing.     

红细胞非惯性升力对血液流动的影响

目的 为准确模拟血流,研究红细胞变形性对血液流动的影响。方法 基于血液流变特性和红细胞力学特性分析,对现有血液两相流流动模型进行改进,改进模型中考虑了易变形红细胞受剪切流场或血管壁面作用而产生的非惯性升力的影响。利用改进模型对多个不同直径血管内的血液流动进行模拟。结果 由红细胞所受非惯性升力导致的径向运动对血管内红细胞体积分数、运动速度分布有明显影响;当血管直径为0.1~3.0 mm时,用改进模型得到的血液相对黏度的模拟值与测量值接近。结论 非惯性升力是血流呈现Fahraeus-Lindqvist效应的主要原因之一。考虑非惯性升力的改进模型可以准确模拟血液流动,为循环系统诊疗机制和细胞分选等过程的模拟提供更为准确的方法。     

Anisotropy of light propagation in human skin

Using spatially resolved, steady state diffuse reflectometry, a directional dependence was found in the propagation of visible and near infrared light through human skin in vivo. The skin's reduced scattering coefficient mu(s)' varies by up to a factor of two between different directions of propagation at the same position. This anisotropy is believed to be caused by the preferential orientation of collagen fibres in the dermis, as described by Langer's skin tension lines. Monte Carlo simulations that examine the effect of partial collagen fibre orientation support this hypothesis. The observation has consequences for non-invasive diagnostic methods relying on skin optical properties, and it could be used non-invasively to determine the direction of lines of cleavage in order to minimize scars due to surgical incisions.     

Microconfined flow behavior of red blood cells

Red blood cells (RBCs) perform essential functions in human body, such as gas exchange between blood and tissues, thanks to their ability to deform and flow in the microvascular network. The high RBC deformability is mainly due to the viscoelastic properties of the cell membrane. Since an impaired RBC deformability could be found in some diseases, such as malaria, sickle cell anemia, diabetes and hereditary disorders, there is the need to provide further insight into measurement of RBC deformability in a physiologically relevant flow field. Here, RBCs deformability has been studied in terms of the minimum apparent plasma-layer thickness by using high-speed video microscopy of RBCs flowing in cylindrical glass capillaries. An in vitro systematic microfluidic investigation of RBCs in micro-confined conditions has been performed, resulting in the determination of the RBCs time recovery constant, RBC volume and surface area and RBC membrane shear elastic modulus and surface viscosity. It has been noticed that the deformability of RBCs induces cells aggregation during flow in microcapillaries, allowing the formation of clusters of cells. Overall, our results provide a novel technique to estimate RBC deformability and also RBCs collective behavior, which can be used for the analysis of pathological RBCs, for which reliable quantitative methods are still lacking.     

Validity of a theoretical model to examine blood oxygenation dependent optoacoustics

A theoretical model investigating the dependence of optoacoustic (OA) signal on blood oxygen saturation (SO(2)) is discussed. The derivations for the nonbandlimited and bandlimited OA signals from many red blood cells (RBCs) are presented. The OA field generated by many RBCs was obtained by summing the OA field emitted by each RBC approximated as a fluid sphere. A Monte Carlo technique was employed generating the spatial organizations of RBCs in two-dimensional. The RBCs were assumed to have the same SO(2) level in a simulated configuration. The fractional number of oxyhemoglobin molecules, confined in a cell, determined the cellular SO(2) and also defined the blood SO(2). For the nonbandlimited case, the OA signal amplitude decreased and increased linearly with blood SO(2) when illuminated by 700 and 1000 nm radiations, respectively. The power spectra exhibited similar trends over the entire frequency range (MHz to GHz). For the bandlimited case, three acoustic receivers with 2, 10, and 50 MHz as the center frequencies were considered. The linear variations of the OA amplitude with blood SO(2) were also observed for each receiver at those laser sources. The good agreement between simulated and published experimental results validates the model qualitatively.     

Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range

The optical parameters absorption coefficient, scattering coefficient, and the anisotropy factor of platelets (PLTs) suspended in plasma and cell-free blood plasma are determined by measuring the diffuse reflectance, total and diffuse transmission, and subsequently by inverse Monte Carlo simulation. Furthermore, the optical behavior of PLTs and red blood cells suspended in plasma are compared with those suspended in saline solution. Cell-free plasma shows a higher scattering coefficient and anisotropy factor than expected for Rayleigh scattering by plasma proteins. The scattering coefficient of PLTs increases linearly with the PLT concentration. The existence of physiological concentrations of leukocytes has no measurable influence on the absorption and scattering properties of whole blood. In summary, red blood cells predominate over the other blood components by two to three orders of magnitude with regard to absorption and effective scattering. However, substituting saline solution for plasma leads to a significant increase in the effective scattering coefficient and therefore should be taken into consideration.     

Microfluidic interactions between red blood cells and drug carriers by image analysis techniques

Blood is a complex biological fluid composed of deformable cells and platelets suspended in plasma, a protein-rich liquid. The peculiar nature of blood needs to be considered when designing a drug delivery strategy based on systemically administered carriers. Here, we report on an in vitro fluid dynamic investigation of the influence of the microcapillary flow of red blood cells (RBCs) on micron-sized carriers by high-speed imaging methods. The experiments were carried out in a 50 µm diameter glass capillary that mimicked the hydrodynamic conditions of human microcirculation. Spherical μ-particles (μ-Ps), with sizes ranging between 0.5 and 3 µm, were tested. Images of the flowing RBCs and μ-Ps were acquired by a high- speed/high-magnification microscopy. The transport and distribution of rigid particles in a suspension of RBCs under shear flow were investigated by analyzing: (i) the velocity profile of both μ-Ps and RBCs in the capillary; (ii) the radial distribution of μ-Ps in the presence of RBCs; (iii) the migration of μ-Ps towards the vessel wall due to their hydrodynamic interactions with RBCs. This study suggests that the therapeutic efficacy of μ-Ps could be ultimately affected by their interactions with the flowing RBCs in the vasculature.     

Determination of radiotherapy X-ray spectra using a screen-film system

A method to determine the X-ray spectrum delivered by a medical linear accelerator is presented. This method consists of an analytical calculation of the primary spectrum using the Schiff bremsstrahlung cross-section formula. A correction factor that accounts for the scatter component of the spectrum is estimated by comparing the signal in two screen-film systems to a theoretical prediction using a model of energy deposition in such detectors. The model makes use of the quantum absorption efficiency and the average energy deposited per interacting photon concepts. These two quantities are calculated by means of Monte Carlo simulations of the screen-film systems used. This method is capable of determining the spectrum as a function of the spatial position across a plane perpendicular to the beam central axis. It does not, however, render information about the direction cosines of the X-ray fluence crossing such a plane, a requirement in order to produce a full phase-space file that can be used in conjunction with a Monte Carlo dose calculation engine.     

Experimental validation of Monte Carlo modeling of fluorescence in tissues in the UV-visible spectrum

The goal of the work is to experimentally verify Monte Carlo modeling of fluorescence and diffuse reflectance measurements in turbid, tissue phantom models. In particular, two series of simulations and experiments, in which one optical parameter (absorption or scattering coefficient) is varied while the other is fixed, are carried out to assess the effect of the absorption coefficient (mu(a)) and scattering coefficient (mu(s)) on the fluorescence and diffuse reflectance measured from a turbid medium. Moreover, simulations and experiments are carried out for several fiber optic probe geometries that are designed to sample small tissue volumes. Additionally, a group of conversion expressions are derived to convert the optical properties and fluorescence quantum yield measured from tissue phantoms for use in Monte Carlo simulations. The conversions account for the differences between the definitions of the absorption coefficient and fluorescence quantum yield of fluorophores in a tissue phantom model and those in a Monte Carlo simulation. The results indicate that there is good agreement between the simulated and experimentally measured results in most cases. This dataset can serve as a systematic validation of Monte Carlo modeling of fluorescent light propagation in tissues. The simulations are carried out for a wide range of absorption and scattering coefficients as well as ratios of scattering coefficient to absorption coefficient, and thus would be applicable to tissue optical properties over a wide wavelength range (UV-visible/near infrared). The fiber optic probe geometries that are modeled in this study include those commonly used for measuring fluorescence from tissues in practice.     

Determination of the tissue attenuation factor along two major axes of a high dose rate (HDR) 192Ir source.

Quantitative information on photon scattering around brachytherapy sources is needed to develop dose calculation formalisms capable of predicting dosimetric parameters with minimal empiricism. Photon absorption and scatter around brachytherapy sources can be characterized using the tissue attenuation factor, defined as the ratio of dose in water to water kerma in free space. In this study, the tissue attenuation factor along two major axes of a high dose rate (HDR) 192Ir source was determined by TLD measurements and MCNP Monte Carlo calculations. A calculational method is also suggested to derive the tissue attenuation factor along the longitudinal source axis from the factor along the transverse axis, using published anisotropy data as input. TLD and Monte Carlo results agreed with each other for both source axes within the statistical uncertainty (approximately +/- 5%) of Monte Carlo calculations. Comparison with published data, available only for the transverse source axis, also showed good agreement within +/- 5%. The shape and magnitude of the tissue attenuation factor are found to be remarkably different between the two axes. The tissue attenuation factor reaches a maximum value of about 1.4 at 8 cm from the source along the longitudinal source axis, while a maximum value of about 1.04 occurs at 3-4 cm from the source along the transverse axis. The calculated tissue attenuation factor along the longitudinal source axis generally reproduced the TLD and Monte Carlo results within +/- 5% at most radial distances.     

Visualizing depth and thickness of a local blood region in skin tissue using diffuse reflectance images

A method is proposed for visualizing the depth and thickness distribution of a local blood region in skin tissue using diffuse reflectance images at three isosbestic wavelengths of hemoglobin: 420, 585, and 800 nm. Monte Carlo simulation of light transport specifies a relation among optical densities, depth, and thickness of the region under given concentrations of melanin in epidermis and blood in dermis. Experiments with tissue-like agar gel phantoms indicate that a simple circular blood region embedded in scattering media can be visualized with errors of 6% for the depth and 22% for the thickness to the given values. In-vivo measurements on human veins demonstrate that results from the proposed method agree within errors of 30 and 19% for the depth and thickness, respectively, with values obtained from the same veins by the conventional ultrasound technique. Numerical investigation with the Monte Carlo simulation of light transport in the skin tissue is also performed to discuss effects of deviation in scattering coefficients of skin tissue and absorption coefficients of the local blood region from the typical values of the results. The depth of the local blood region is over- or underestimated as the scattering coefficients of epidermis and dermis decrease or increase, respectively, while the thickness of the region agrees well with the given values below 1.2 mm. Decreases or increases of hematocrit value give over- or underestimation of the thickness, but they have almost no influence on the depth.