Skin and cutaneous melanocytic lesion simulation in biomedical optics with multilayered phantoms

The complex inner layered structure of skin influences the photon diffusion inside the cutaneous tissues and determines the reflectance spectra formation. Phantoms are very useful tools to understand the biophysical meaning of parameters involved in light propagation through the skin. To simulate the skin reflectance spectrum, we realized a multilayered skin-like phantom and a multilayered skin phantom with a melanoma-like phantom embedded inside. Materials used were Al(2)O(3) particles, melanin of sepia officinalis and a calibrator for haematology systems dispersed in transparent silicon. Components were optically characterized with indirect techniques. Reflectance phantom spectra were compared with average values of in vivo spectra acquired on a sample of 573 voluntary subjects and 132 pigmented lesions. The phantoms' reflectance spectra agreed with those measured in vivo, mimicking the optical behaviour of the human skin. Further, the phantoms were optically stable and easily manageable, and represented a valid resource in spectra formation comprehension, in diagnostic laser applications and simulation model implementation, such as the Monte Carlo code for non-homogeneous media.     

Changes in tissue optical properties due to radio-frequency ablation of myocardium

The optical properties of pig heart tissue were measured after in vivo ablation therapy had been performed during open-heart surgery. In vitro samples of normal and ablated tissue were subjected to measurements with an optically integrating sphere set-up in the region 470–900 nm. Three independent measurements were made: total transmittance, total reflectance and collimated transmittance, which made it possible to extract the absorption and scattering coefficients and the scattering anisotropy factor g, using an inverse Monte Carlo model. Between 470 and 700 nm, only the reduced scattering coefficient and absorption could be evaluated. The absorption spectra were fitted to known tissue chromophore spectra, so that the concentrations of haemoglobin and myoglobin could be estimated. The reduced scattering coefficient was compared with Mie computations to provide Mie equivalent average radii. Most of the absorption was from myoglobin, whereas haemoglobin absorption was negligible. Metmyoglobin was formed in the ablated tissue, which could yield a spectral signature to distinguish the ablated tissue with a simple optical probe to monitor the ablation therapy. The reduced scattering coefficient increased by, on average, 50% in the ablated tissue, which corresponded to a slight decrease in the Mie equivalent radius.     

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.     

VarianClinaciX15MeV光子束能谱重建

目的：精确重建VarianClinaciX15MeV光子束能谱。方法：利用先验模型和遗传算法,以光子束中轴百分深度剂量（PDD）为基础数据实现医用直线加速器光子能谱重建。1．EGS模拟仿真VarianClinacix治疗头和标准水模体,获得15MeV光子束的模拟能谱以及单能光子中轴PDD数据;2．根据测量得到的中轴PDD数据以及模拟得到的单能光子中轴PDD数据,运用遗传算法优化求解先验模型的参数：3．将优化后的先验模型所计算的结果作为初始化种群．再用遗传算法二次优化重建光子能谱。结果：重建能谱与蒙特卡洛模拟得到的能谱具有良好的一致性,相关系数为0．9970;重建能谱的平均能量与由相空间文件分析所得平均能量的相对误差为1．16％;根据重建能谱计算得到的中轴PDD数据与实际测量的中轴PDD数据之间的相关系数为O．9999。结论：利用先验模型和遗传算法进行光子束能谱重建可靠有效．具有实用价值。     

白癜风皮肤的反射光谱及其Monte Carlo模拟

测试并研究了具有三种不同肤色的白癜风皮肤的反射光谱，在皮肤组织病理检验的基础上，建立了三色白癜风皮肤的光学模型，讨论了该皮肤的黑色素含量与分布，并进行Monle Carlo模拟计算。研究表明，白癜风皮肤，特别是具有不同肤色的白癜风，可作为一个较好的研究对象，用于探测皮肤黑色素分布或其他光学特性；反射光谱可用于皮肤表层黑色素的研究，特别是在表皮层黑色素缺失的情况下，可探知较深层（如真皮层）的黑色素含量与分布；采用Monte Carlo模拟，可以重现实测的皮肤光谱特性，并可预言皮肤组织中某些生化物质的存在。     

In vivo determination of the optical properties of muscle with time-resolved reflectance using a layered model

We have investigated the possibility of determining the optical coefficients of muscle in the extremities with in vivo time-resolved reflectance measurements using a layered model. A solution of the diffusion equation for two layers was fitted to three-layered Monte Carlo calculations simulating the skin, the subcutaneous fat and the muscle. Relative time-resolved reflectance data at two distances were used to derive the optical coefficients of the layers. We found for skin and subcutaneous fat layer thicknesses (l2) of up to 10 mm that the estimated absorption coefficients of the second layer of the diffusion model have differences of less than 20% compared with those of the muscle layer of the Monte Carlo simulations if the thickness of the first layer of the diffusion model is also fitted. If l2 is known, the differences are less than 5%, whereas the use of a semi-infinite model delivers differences of up to 55%. Even if l2 is only approximately known the absorption coefficient of the muscle can be determined accurately. Experimentally, the time-resolved reflectance was measured on the forearms of volunteers at two distances from the incident beam by means of a streak camera. The thicknesses of the tissues involved were determined by ultrasound. The optical coefficients were derived from these measurements by applying the two-layered diffusion model, and results in accordance with the theoretical studies were observed.     

A library based fitting method for visual reflectance spectroscopy of human skin

The diffuse reflectance spectrum of human skin in the visible region (400-800 nm) contains information on the concentrations of chromophores such as melanin and haemoglobin. This information may be extracted by fitting the reflectance spectrum with an optical diffusion based analytical expression applied to a layered skin model. With the use of the analytical expression, it is assumed that light transport is dominated by scattering. For port wine stain (PWS) and highly pigmented human skin, however, this assumption may not be valid resulting in a potentially large error in visual reflectance spectroscopy (VRS). Monte Carlo based techniques can overcome this problem but are currently too computationally intensive to be combined with previously used fitting procedures. The fitting procedure presented herein is based on a library search which enables the use of accurate reflectance spectra based on forward Monte Carlo simulations or diffusion theory. This allows for accurate VRS to characterize chromophore concentrations in PWS and highly pigmented human skin. The method is demonstrated using both simulated and measured reflectance spectra. An additional advantage of the method is that the fitting procedure is very fast.     

Quantifying tumor-selective radiation dose enhancements using gold nanoparticles: a monte carlo simulation study

Gold nanoparticles can enhance the biological effective dose of radiation delivered to tumors, but few data exist to quantify this effect. The purpose of this project was to build a Monte Carlo simulation model to study the degree of dose enhancement achievable with gold nanoparticles. A Monte Carlo simulation model was first built using Geant4 code. An Ir-192 brachytherapy source in a water phantom was simulated and the calculation model was first validated against previously published data. We then introduced up to 10¹³ gold nanospheres per cm³ into the water phantom and examined their dose enhancement effect. We compared this enhancement against a gold-water mixture model that has been previously used to attempt to quantify nanoparticle dose enhancement. In our benchmark test, dose-rate constant, radial dose function, and two-dimensional anisotropy function calculated with our model were within 2% of those reported previously. Using our simulation model we found that the radiation dose was enhanced up to 60% with 10¹³ gold nanospheres per cm³ (9.6% by weight) in a water phantom selectively around the nanospheres. The comparison study indicated that our model more accurately calculated the dose enhancement effect and that previous methodologies overestimated the dose enhancement up to 16%. Monte Carlo calculations demonstrate that biologically-relevant radiation dose enhancement can be achieved with the use of gold nanospheres. Selective tumor labeling with gold nanospheres may be a strategy for clinically enhancing radiation effects. This study was partially funded by a grant from the U. S. Department of Defense Breast Cancer Research Program (W81XWH-06-1-0672) and by the institutional core grant (CA 16672). The authors also wish to acknowledge the Department of Scientific Publications at The University of Texas M. D. Anderson Cancer Center for its editorial assistance during the preparation of this article.     

Multi-layer imaging of human organs by measurement of laser backscattered radiation

Laser backscattered radiations from tissue phantoms and human forearms are measured by a reflectance imager. Laser radiations are guided by an optical fibre, and the backscattered radiations are collected by three optical fibres in the measurement probe assembly, placed at distances of 2 mm, 4 mm and 6 mm from the input fibre. By placing the measurement probe on the phantom or tissue surface and matching the outline on the computer monitor, the reflectance data from the organ or the phantom are collected. These data, after digitisation, interpolation and filtering, are colour coded and displayed on the computer monitor. Using this imaging procedure, the abnormalities embedded at different depths in the phantoms are located. The structural changes due to colour, composition and blood flow in the multi-layer of human forearms of various subjects are qualitatively shown in reflectance images obtained by this procedure.     

Multi-layer imaging of human organs by measurement of laser backscattered radiation

Laser backscattered radiations from tissue phantoms and human forearms are measured by a reflectance imager. Laser radiations are guided by an optical fibre, and the backscattered radiations are collected by three optical fibres in the measurement probe assembly, placed at distances of 2 mm, 4 mm and 6 mm from the input fibre. By placing the measurement probe on the phantom or tissue surface and matching the outline on the computer monitor, the reflectance data from the organ or the phantom are collected. These data, after digitisation, interpolation and filtering, are colour coded and displayed on the computer monitor. Using this imaging procedure, the abnormalities embedded at different depths in the phantoms are located. The structural changes due to colour, composition and blood flow in the multi-layer of human forearms of various subjects are qualitatively shown in reflectance images obtained by this procedure.     

Numerical study of reflectance imaging using a parallel Monte Carlo method

Reflectance imaging of biological tissues with visible and near-infrared light has the significant potential to provide a noninvasive and safe imaging modality for diagnosis of dysplastic and malignant lesions in the superficial tissue layers. The difficulty in the extraction of optical and structural parameters lies in the lack of efficient methods for accurate modeling of light scattering in biological tissues of turbid nature. We present a parallel Monte Carlo method for accurate and efficient modeling of reflectance images from turbid tissue phantoms. A parallel Monte Carlo code has been developed with the message passing interface and evaluated on a computing cluster with 16 processing elements. The code was validated against the solutions of the radiative transfer equation on the bidirectional reflection and transmission functions. With this code we investigated numerically the dependence of reflectance image on the imaging system and phantom parameters. The contrasts of reflectance images were found to be nearly independent of the numerical aperture (NA) of the imaging camera despite the fact that reflectance depends on the NA. This enables efficient simulations of the reflectance images using an NA at 1.00. Using heterogeneous tissue phantoms with an embedded region simulating a lesion, we investigated the correlation between the reflectance image profile or contrast and the phantom parameters. It has been shown that the image contrast approaches 0 when the single-scattering albedos of the two regions in the heterogeneous phantoms become matched. Furthermore, a zone of detection has been demonstrated for determination of the thickness of the embedded region and optical parameters from the reflectance image profile and contrast. Therefore, the utility of the reflectance imaging method with visible and near-infrared light has been firmly established. We conclude from these results that the optical parameters of the embedded region can be determined inversely from reflectance images acquired with full-field illumination at multiple incident angles or multiple wavelengths.     

Optical and acoustic properties at 1064 nm of polyvinyl chloride-plastisol for use as a tissue phantom in biomedical optoacoustics

A novel optoacoustic phantom made of polyvinyl chloride-plastisol (PVCP) for optoacoustic studies is described. The optical and acoustic properties of PVCP were measured. Titanium dioxide (TiO2) powder and black plastic colour (BPC) were used to introduce scattering and absorption, respectively, in the phantoms. The optical absorption coefficient (mua) at 1064 nm was determined using an optoacoustic method, while diffuse reflectance measurements were used to obtain the optical reduced scattering coefficient (mu's). These optical properties were calculated to be mua = (12.818 +/- 0.001)ABPC cm(-1) and mu's = (2.6 +/- 0.2)S(TiO2) + (1.4 +/- 0.1) cm(-1), where ABPC is the BPC per cent volume concentration, and S(TiO2) is the TiO2 volume concentration (mg mL(-1)). The speed of sound in PVCP was measured to be (1.40 +/- 0.02) x 10(3) m s(-1) using the pulse echo transmit receive method, with an acoustic attenuation of (0.56 +/- 1.01) f(1.51+/-0.06)MHz (dB cm(-1)) in the frequency range of 0.61-1.25 MHz, and a density, calculated by measuring the displacement of water, of 1.00 +/- 0.04 g cm(-3). The speed of sound and density of PVCP are similar to tissue, and together with the user-adjustable optical properties, make this material well suited for developing tissue-equivalent phantoms for biomedical optoacoustics.     

DPM蒙卡方法在放疗剂量计算中的应用研究

目的:探讨最新推出基于蒙特卡罗方法的DPM(dose planning method)程序在放疗剂量计算中的应用,研究DPM程序计算放疗剂量的准确性及其临床应用的可行性。方法:对DPM源文件编译形成四个可执行文件,使其能在Windows系统下运行。(1)通过借助蒙卡BEAMnrc程序模拟我院Varian Clinac 21EX直线加速器治疗头,得到其相空间文件,并计算出SSD=100cm处的相空间(Phase Space)数据。(2)使用BEAMDP程序对该相空间文件进行能谱分析,获取到6MV-X线能谱分布。(3)修改DPM源程序,使之能调用该能谱。(4)DPM计算出水模体内百分深度剂量并用MATLAB软件显示PDD曲线分布,与实际测量进行拟合。(5)DPM计算非均匀组织内方野剂量,相同条件下与实测量、TPS计算值进行了比较。结果:蒙卡DPM程序调用直线加速器能谱计算水模体内的PDD曲线与实测曲线的拟合完全吻合,证明了DPM程序调用能谱方法可行而且计算准确。DPM蒙卡程序在非均匀组织中的计算也是准确的。结论:DPM蒙卡方法可应用实现组织中放疗剂量计算的研究。     

Non-invasive determination of muscle blood flow in the extremities from laser Doppler spectra

We investigate theoretically the non-invasive determination of blood flow in muscles of the extremities using laser Doppler measurements. Laser Doppler spectra are calculated using Monte Carlo simulations and solutions of the correlation diffusion equation. The extremities are modelled as a two-layered turbid medium. The first layer represents the skin and subcutaneous fat layer and the second layer the muscle. It is shown that the absolute root-mean-square velocity of the blood in the muscle layer can be accurately derived in many practical cases if the laser Doppler spectra are measured at a distance which is sufficiently far from the source, and if the optical properties of the muscle are simultaneously determined.     

基于蒙特卡洛方法和数字体模的质子治疗设施屏蔽优化设计

目的:评估采用蒙特卡洛（MC）模拟方法和中国科学技术大学数字人体模型（USTC体模）在质子治疗设施中的辐射屏蔽优化设计。方法:使用MC模拟方法和USTC体模计算数字体模处于不同位置时在不同部位的当量剂量率（EDR），对安徽省合肥市离子医学中心（HIMC）的新型质子治疗设施的屏蔽设计进行评估，并将其与采用经验公式计算得出的EDR进行比较。结果:使用铁靶时，经验公式计算得出的EDR值比MC模拟方法得到的结果偏高27.6倍；使用水靶时，经验公式计算结果较MC模拟结果高36.6倍，说明使用经验公式进行屏蔽计算将使得剂量被高估，从而导致成本增加，不符合辐射防护最优化原则。结论:利用USTC体模对质子治疗设施进行基于MC模拟的屏蔽计算可以得到更加准确和优化的结果。     

Establishing an Initial Electron Beam Model with Monte Carlo Simulation for a Single 6 MV X-ray Medical Linac Based on Particle Dynamics Characteristics

Objective：In this study, we try to establish an initial electron beam model by combining Monte Carlo simulation method with particle dynamic calculation （TRSV） for the single 6 MV X-ray accelerating waveguide of BJ-6 medical linac. Methods and Materials ： 1. We adapted the treatment head configuration of BJ-6 medical linac made by Beijing Medical Equipment Institute （BMEI） as the radiation system for this study. 2. Use particle dynamics calculation code called TRSV to drive out the initial electron beam parameters of the energy spectrum, the spatial intensity distribution, and the beam incidence angle. 3. Analyze the 6 MV X-ray beam characteristics of PDDc , OARc in a water phantom by using Monte Carlo simulation （ BEAMnrc, DOSXYZnrc） for a preset of the initial electron beam parameters which have been determined by TRSV, do the comparisons of the measured results of PDDm, OARm in a real water phantom, and then use the deviations of calculated and measured results to slightly modify the initial electron beam model back and forth until the deviations meet the error less than 2%. Results：The deviations between the Monte Carlo simulation results of percentage depth doses at PDDc and off-axis ratios OARc and the measured results of PDDm and OARm in a water phantom were within 2%. Conclusion：When doing the Monte Carlo simulation to determine the parameters of an initial electron beam for a particular medical linac like B J-6, modifying some parameters based on the particle dynamics calculation code would give some more reasonable and more acceptable results.     

Comparison of dose calculation algorithms with Monte Carlo methods for photon arcs

The objective of this study is to seek an accurate and efficient method to calculate the dose distribution of a photon arc. The algorithms tested include Monte Carlo, pencil beam kernel (PK), and collapsed cone convolution (CCC). For the Monte Carlo dose calculation, EGS4/DOSXYZ was used. The SRCXYZ source code associated with the DOSXYZ was modified so that the gantry angle of a photon beam would be sampled uniformly within the arc range about an isocenter to simulate a photon arc. Specifically, photon beams (6/18 MV, 4 x 4 and 10 x 10 cm2) described by a phase space file generated by BEAM (MCPHS), or by two point sources with different photon energy spectra (MCDIV) were used. These methods were used to calculate three-dimensional (3-D) distributions in a PMMA phantom, a cylindrical water phantom, and a phantom with lung inhomogeneity. A commercial treatment planning system was also used to calculate dose distributions in these phantoms using equivalent tissue air ratio (ETAR), PK and CCC algorithms for inhomogeneity corrections. Dose distributions for a photon arc in these phantoms were measured using a RK ion chamber and radiographic films. For homogeneous phantoms, the measured results agreed well (approximately 2% error) with predictions by the Monte Carlo simulations (MCPHS and MCDIV) and the treatment planning system for the 180 degrees and 360 degrees photon arcs. For the dose distribution in the phantom with lung inhomogeneity with a 90 degrees photon arc, the Monte Carlo calculations agreed with the measurements within 2%, while the treatment planning system using ETAR, PK and CCC underestimated or overestimated the dose inside the lung inhomogeneity from 6% to 12%.     

A polygon-surface reference Korean male phantom (PSRK-Man) and its direct implementation in Geant4 Monte Carlo simulation

Even though the hybrid phantom embodies both the anatomic reality of voxel phantoms and the deformability of stylized phantoms, it must be voxelized to be used in a Monte Carlo code for dose calculation or some imaging simulation, which incurs the inherent limitations of voxel phantoms. In the present study, a voxel phantom named VKH-Man (Visible Korean Human-Man), was converted to a polygon-surface phantom (PSRK-Man, Polygon-Surface Reference Korean-Man), which was then adjusted to the Reference Korean data. Subsequently, the PSRK-Man polygon phantom was directly, without any voxelization process, implemented in the Geant4 Monte Carlo code for dose calculations. The calculated dose values and computation time were then compared with those of HDRK-Man (High Definition Reference Korean-Man), a corresponding voxel phantom adjusted to the same Reference Korean data from the same VKH-Man voxel phantom. Our results showed that the calculated dose values of the PSRK-Man surface phantom agreed well with those of the HDRK-Man voxel phantom. The calculation speed for the PSRK-Man polygon phantom though was 70-150 times slower than that of the HDRK-Man voxel phantom; that speed, however, could be acceptable in some applications, in that direct use of the surface phantom PSRK-Man in Geant4 does not require a separate voxelization process. Computing speed can be enhanced, in future, either by optimizing the Monte Carlo transport kernel for the polygon surfaces or by using modern computing technologies such as grid computing and general-purpose computing on graphics processing units programming.     

Spectroscopic method for determination of the absorption coefficient in brain tissue

I use Monte Carlo simulations and phantom measurements to characterize a probe with adjacent optical fibres for diffuse reflectance spectroscopy during stereotactic surgery in the brain. Simulations and measurements have been fitted to a modified Beer-Lambert model for light transport in order to be able to quantify chromophore content based on clinically measured spectra in brain tissue. It was found that it is important to take the impact of the light absorption into account when calculating the apparent optical path length, lp, for the photons in order to get good estimates of the absorption coefficient, μa. The optical path length was found to be well fitted to the equation lp=a+b ln(Is)+c ln(μa)+d ln(Is)ln(μa), where Is is the reflected light intensity for scattering alone (i.e., zero absorption). Although coefficients a-d calculated in this study are specific to the probe used here, the general form of the equation should be applicable to similar probes.     

Monte Carlo verification of polymer gel dosimetry applied to radionuclide therapy: a phantom study

This study evaluates the dosimetric performance of the polymer gel dosimeter 'Methacrylic and Ascorbic acid in Gelatin, initiated by Copper' and its suitability for quality assurance and analysis of I-131-targeted radionuclide therapy dosimetry. Four batches of gel were manufactured in-house and sets of calibration vials and phantoms were created containing different concentrations of I-131-doped gel. Multiple dose measurements were made up to 700 h post preparation and compared to equivalent Monte Carlo simulations. In addition to uniformly filled phantoms the cross-dose distribution from a hot insert to a surrounding phantom was measured. In this example comparisons were made with both Monte Carlo and a clinical scintigraphic dosimetry method. Dose-response curves generated from the calibration data followed a sigmoid function. The gels appeared to be stable over many weeks of internal irradiation with a delay in gel response observed at 29 h post preparation. This was attributed to chemical inhibitors and slow reaction rates of long-chain radical species. For this reason, phantom measurements were only made after 190 h of irradiation. For uniformly filled phantoms of I-131 the accuracy of dose measurements agreed to within 10% when compared to Monte Carlo simulations. A radial cross-dose distribution measured using the gel dosimeter compared well to that calculated with Monte Carlo. Small inhomogeneities were observed in the dosimeter attributed to non-uniform mixing of monomer during preparation. However, they were not detrimental to this study where the quantitative accuracy and spatial resolution of polymer gel dosimetry were far superior to that calculated using scintigraphy. The difference between Monte Carlo and gel measurements was of the order of a few cGy, whilst with the scintigraphic method differences of up to 8 Gy were observed. A manipulation technique is also presented which allows 3D scintigraphic dosimetry measurements to be compared to polymer gel dosimetry measurements without generating misleading errors due to the limited spatial resolution.