Monte Carlo calculations of radiotherapy dose in “homogeneous” anatomy

Given the substantial literature on the use of Monte Carlo (MC) simulations to verify treatment planning system (TPS) calculations of radiotherapy dose in heterogeneous regions, such as head and neck and lung, this study investigated the potential value of running MC simulations of radiotherapy treatments of nominally homogeneous pelvic anatomy. A pre-existing in-house MC job submission and analysis system, built around BEAMnrc and DOSXYZnrc, was used to evaluate the dosimetric accuracy of a sample of 12 pelvic volumetric arc therapy (VMAT) treatments, planned using the Varian Eclipse TPS, where dose was calculated with both the Analytical Anisotropic Algorithm (AAA) and the Acuros (AXB) algorithm. In-house TADA (Treatment And Dose Assessor) software was used to evaluate treatment plan complexity, in terms of the small aperture score (SAS), modulation index (MI) and a novel exposed leaf score (ELS/ELA). Results showed that the TPS generally achieved closer agreement with the MC dose distribution when treatments were planned for smaller (single-organ) targets rather than larger targets that included nodes or metastases. Analysis of these MC results with reference to the complexity metrics indicated that while AXB was useful for reducing dosimetric uncertainties associated with density heterogeneity, the residual TPS dose calculation uncertainties resulted from treatment plan complexity and TPS model simplicity. The results of this study demonstrate the value of using MC methods to recalculate and check the dose calculations provided by commercial radiotherapy TPSs, even when the treated anatomy is assumed to be comparatively homogeneous, such as in the pelvic region.     

Monte Carlo commissioning of radiotherapy LINAC—Introducing an improved methodology

PurposeMonte Carlo (MC) commissioning of medical linear accelerator (LINAC) is a time-consuming process involving a comparison between measured and simulated cross beam/lateral profiles and percentage depth doses (PDDs) for various field sizes. An agreement between these two data sets is sought by trial and error method while varying the incident electron beam parameters, such as electron beam energy or width, etc. This study aims to improve the efficiency of MC commissioning of a LINAC by assessing the feasibility of using a limited number of simulated PDDs.Materials and methodsUsing EGSnrc codes, a Varian Clinac 2100 unit has been commissioned for 6 MV photon beam, and a methodology has been proposed to identify the incident electron beam parameters in a speedier fashion. Impact of voxel size in 3-dimensions and cost functions used for comparison of the measured and simulated data have been investigated along with the role of interpolation.ResultsA voxel size of 1 × 1×0.5 cm³ has been identified as suitable for accurate and fast commissioning of the LIANC. The optimum number of simulated PDDs (required for further interpolation) has been found to be five.ConclusionThe present study suggests that PDDs alone at times can be insufficient for an unambiguous commissioning process and should be supported by including the lateral beam profiles in the process.     

Evaluation of PENFAST – A fast Monte Carlo code for dose calculations in photon and electron radiotherapy treatment planning

The aim of the present study is to demonstrate the potential of accelerated dose calculations, using the fast Monte Carlo (MC) code referred to as PENFAST, rather than the conventional MC code PENELOPE, without losing accuracy in the computed dose. For this purpose, experimental measurements of dose distributions in homogeneous and inhomogeneous phantoms were compared with simulated results using both PENELOPE and PENFAST. The simulations and experiments were performed using a Saturne 43 linac operated at 12 MV (photons), and at 18 MeV (electrons). Pre-calculated phase space files (PSFs) were used as input data to both the PENELOPE and PENFAST dose simulations. Since depth–dose and dose profile comparisons between simulations and measurements in water were found to be in good agreement (within ±1% to 1 mm), the PSF calculation is considered to have been validated. In addition, measured dose distributions were compared to simulated results in a set of clinically relevant, inhomogeneous phantoms, consisting of lung and bone heterogeneities in a water tank. In general, the PENFAST results agree to within a 1% to 1 mm difference with those produced by PENELOPE, and to within a 2% to 2 mm difference with measured values. Our study thus provides a pre-clinical validation of the PENFAST code. It also demonstrates that PENFAST provides accurate results for both photon and electron beams, equivalent to those obtained with PENELOPE. CPU time comparisons between both MC codes show that PENFAST is generally about 9–21 times faster than PENELOPE.     

Continuous fractional component Monte Carlo simulations of high-density adsorption in metal–organic frameworks

The continuous fractional component Monte Carlo method, which was designed to overcome difficulties with insertions and deletions of molecules, is modified to include configurational bias Monte Carlo methods and is further extended to binary systems. The modified method is shown to correctly predict adsorption of Ar in silicalite, Xe and Kr in HKUST-1, and enantiomers in a homochiral metal–organic framework. The modified method is also found to be approximately an order of magnitude more efficient in inserting and deleting molecules than traditional configurational bias grand canonical Monte Carlo simulations in dense systems.     

Monte Carlo simulations of vapour–liquid phase equilibrium and microstructure for the system containing azeotropes

Abstract

Phase equilibrium data of the mixtures including alcohols, esters and organic acids are of first interest particularly to design and optimise biodiesel production and reactive distillation processes. In this work, vapour–liquid phase equilibrium of these systems was simulated at low pressure using Gibbs ensemble Monte Carlo method. All Lennard–Jones parameters of pseudo-atoms involved in the systems were derived from previous parametrisations of TraPPE-UA force field. The Fourier coefficients of dihedrals encountered in ethyl acetate molecule have been obtained from the quantum calculations. Using this force field, temperature-composition diagrams are well reproduced for ethyl acetate + ethanol, ethyl acetate + methanol at 70.00 kPa and ethyl acetate + acetic acid mixtures at 77.33 kPa. The transferability of this force field to mixtures in these systems is noticeable. Analysis of the microstructure for the ethyl acetate + ethanol and ethyl acetate + acetic acid mixtures was presented. We found that the hydrogen bond networks consist of autoassociation and cross-association and autoassociation occupies the main position as compared with cross association in the ethyl acetate + ethanol mixture. OC_HAc–H_HAc and OC_EtOAc–H_HAc hydrogen bond interactions play a significant role in the phase behaviours or structures of ethyl acetate + acetic acid mixture.     

Fetal radiation dose in three common CT examinations during pregnancy – Monte Carlo study

PurposeTo determine fetal doses in different stages of pregnancy in three common computed tomography (CT) examinations: pulmonary CT angiography, abdomino-pelvic and trauma scan with Monte Carlo (MC) simulations.MethodsAn adult female anthropomorphic phantom was scanned with a 64-slice CT using pulmonary angiography, abdomino-pelvic and trauma CT scan protocols. Three different sized gelatin boluses placed on the phantom’s abdomen simulated different stages of pregnancy. Intrauterine dose was used as a surrogate to a dose absorbed to the fetus. MC simulations were performed to estimate uterine doses. The simulation dose levels were calibrated with volumetric CT dose index (CTDI_vol) measurements and MC simulations in a cylindrical CTDI body phantom and compared with ten point doses measured with metal-oxide-semiconductor field-effect-transistor dosimeters. Intrauterine volumes and uterine walls were segmented and the respective dose volume histograms were calculated.ResultsThe mean intrauterine doses in different stages of pregnancy varied from 0.04 to 1.04 mGy, from 4.8 to 5.8 mGy, and from 9.8 to 12.6 mGy in the CT scans for pulmonary angiography, abdomino-pelvic and trauma CT scans, respectively. MC simulations showed good correlation with the MOSFET measurement at the measured locations.ConclusionsThe three studied examinations provided highly varying fetal doses increasing from sub-mGy level in pulmonary CT angiography to notably higher levels in abdomino-pelvic and trauma scans where the fetus is in the primary exposure range. Volumetric dose distribution offered by MC simulations in an appropriate anthropomorphic phantom provides a comprehensive dose assessment when applied in adjunct to point-dose measurements.     

Monte Carlo simulations in the isothermal-isobaric ensemble: use of a ‘shell’ particle for simulating polyatomic fluids

The recent reformulation of the isothermal-isobaric ensemble requires the use of a ‘shell’ particle to define uniquely the volume of the system, thereby avoiding the redundant counting of configurations. A previous modification of the Monte Carlo method, in which trial moves are generated and accepted consistent with the correct constant pressure partition function, is extended here to the case of polyatomic fluids. With a ‘shell’ molecule, either the centre of mass of the molecule or the location of any one of the atoms within the molecule can be chosen to define the system volume. Ensemble averages obtained with the use of the shell molecule differ from ensemble averages determined with the old (i.e. no shell particle) Monte Carlo algorithm, specifically for small system sizes, although both sets of averages become equal, as they must, in the thermodynamic limit. Monte Carlo simulations in the constant pressure ensemble for various Lennard-Jones polyatomic fluids, both for pure component and binary mixtures, demonstrate these differences for small systems. For mixtures, Monte Carlo simulations may include attempted identity swaps for the shell molecule, as the choice of which component serves as the shell molecule is arbitrary when periodic boundary conditions are applied.     

Does the setup of Monte Carlo simulations influence the calculated properties and effect of gold nanoparticles in radiation therapy?

PurposeTo investigate whether the dose-scoring process of Monte Carlo (MC) simulations of Gold nanoparticles (GNPs) in radiation therapy affects the results.MethodsThe GATE MC toolkit was used to simulate the irradiation of a water phantom containing a single solid or hollow GNP with 250 kVp and 6 MV photons. The dose was scored in 20 nm × 20 nm × 50 μm, 100 nm × 100 nm × 50 μm and 200 nm × 200 nm × 50 μm volumes using dose-scoring voxels of size 1 nm × 1 nm × 50 μm, 10 nm × 10 nm × 50 μm, 50 nm × 50 nm × 50 μm and 100 nm × 100 nm × 50 μm Εxcess dose depth-dose (EDDD) curves and lateral beam profiles were used to compare the dose-scoring voxels.ResultsIn a given volume, neither the EDDD curves nor the lateral beam profiles are affected by the size of the dose-scoring voxels, subject to noise and uncertainty. Certain features of the EDDD curves are clearly seen in larger volumes, but hidden within the uncertainty and noise levels in smaller volumes. For the lateral beam profiles, it is the larger volumes that result in misleading results and the smaller ones that give the expected results. However, the limited statistics result in asymmetries and skewness in the profiles.ConclusionFor a given volume, the dose curves are not affected by the size of the dose-scoring voxels. However, the voxel size may hide or reveal the finer structure of the dose curves and/or may result in misleading curves.     

A new kinetic Monte Carlo scheme with Gibbs ensemble to determine vapour–liquid equilibria

We present a new kinetic Monte Carlo scheme, as an alternative to the Gibbs ensemble Monte Carlo (GEMC) method, to determine vapour–liquid equilibria using a canonical ensemble in a system composed of two boxes. To illustrate the method, we have tested it with two systems: (1) argon over a range of temperatures from below the triple point to close to the critical point; (2) methane and ethane mixtures of various compositions at 180 K. The advantage of the new scheme is that chemical potentials of all components are accurately determined in both boxes. In particular, the chemical potential in the liquid box is determined much more accurately than with the Widom method employed in conventional GEMC simulations.     

The solution conformation of sialyl-α(2→6)-lactose studied by modern NMR techniques and Monte Carlo simulations

Summary We present a comprehensive strategy for detailed characterization of the solution conformations of oligosaccharides by NMR spectroscopy and force-field calculations. Our experimental strategy generates a number of interglycosidic spatial constraints that is sufficiently large to allow us to determine glycosidic linkage conformations with a precision heretofore unachievable. In addition to the commonly used {¹H,¹H} NOE contacts between aliphatic protons, our constraints are: (a) homonuclear NOEs of hydroxyl protons in H₂O to other protons in the oligosaccharide, (b) heteronuclear {¹H,¹³C} NOEs, (c) isotope effects of O¹H/O²H hydroxyl groups on¹³C chemical shifts, and (d) long-range heteronuclear scalar coupling across glycosidic bonds.We have used this approach to study the trisaccharide sialyl-(26)-lactose in aqueous solution. The experimentally determined geometrical constraints were compared to results obtained from force-field calculations based on Metropolis Monte Carlo simulations. The molecule was found to exist in 2 families of conformers. The preferred conformations of the (26)-linkage of the trisaccharide are best described by an equilibrium of 2 conformers with angles at –60° or 180° and of the 3 staggered rotamers of the angle with a predominantgt conformer. Three intramolecular hydrogen bonds, involving the hydroxyl protons on C8 and C7 of the sialic acid residue and on C3 of the reducing-end glucose residue, contribute significantly to the conformational stability of the trisaccharide in aqueous solution. Supplementary material available from the corresponding author: Table containing values for the dihedral angles , , , , and for bond angles , for the six lowest-energy conformations of sialyl-(26)-lactose (1 page).     

Distinct phases of free α-synuclein--a Monte Carlo study

The α-synuclein protein (αS), implicated in Parkinson's disease, shows conformational versatility. It aggregates into β-sheet-rich fibrils, occurs in helical membrane-bound forms, is disordered as a free monomer, and has recently been suggested to have a folded helical tetramer as its main physiological form. Here, we use implicit solvent all-atom Monte Carlo methods to explore the conformational ensemble sampled by the free αS monomer. We analyze secondary structure propensities, size, and topological properties and compare with existing experimental data. Our study suggests that free αS has two distinct phases. One phase has the expected disordered character. The other phase also shows large conformational variability. However, in this phase, the β-strand content is substantial, and the backbone fold shows statistical similarities with that in αS fibrils. Presence of this phase is consistent with data from low-temperature experiments. Conversion of disordered αS to this fibril-like form requires the crossing of a rather large apparent free-energy barrier.     

运用Monte Carlo模拟方法评价林木转化分析法

使用蒙特卡罗模拟(Monte Carlo simulation)方法来评价了林木非平衡单因素随机区组试验资料转化前后的分析效果.为了减少工作量,并使研究结果具有普遍性,采用了5个试验,单因素RCB设计,将多株小区转化成单株小区,研究转化分析法的统计学基础.评价非平衡试验资料转化前后分析法优劣的指标有,(1)有无负的方差分量;(2)参数的偏性,偏性的显著性和均方误大小;(3)试验资料的转化对家系遗传力和单株遗传力估计值大小和误差的影响.经过比较分析发现t(1)转化分析法可以消灭负的方差分量;(2)在参数的偏性、偏性的显著性和均方误大小方面,试验I至III的结果是一致的,除了未转化的资料Vb偏差达到显著水平外,其它参数间的偏差不显著;所有参数的均方误都是未转化的资料大;(3)对试验资料进行转化,有利于提高提高遗传力的大小,降低参数的误差.由于林木造林试验多采用4-8株小区,所以可以得出结论;转化分析法都要优于原模型分析法.建议在林木遗传育种实践中采用转化分析法来处理非平衡试验资料.     

Monte Carlo studies of two-dimensional polymer–solvent systems

The static properties of two-dimensional athermal polymer solutions were studied by performing Monte Carlo lattice simulations using the cooperative motion algorithm (CMA) and taking into account the presence of explicit solvent molecules. The simulations were performed for a wide range of polymer chain lengths N (16–1024) and concentrations φ (0.0156–1). The results obtained for short chains (N?<?256) were in good agreement with those given by previous simulations. For the longest chains (512 or 1024 beads), some unexpected behavior was observed in the dilute and semidilute regimes. A pronounced change in the concentration dependence of chain size and shape was observed below a certain critical concentration (0.6 for the longest chains under consideration, consisting of 1024 beads). Longer chains became more extended below this concentration. The behavior of the single-chain structure factor confirmed these changes in the fractal dimension of the chain as a function of the concentration. The observed phenomena are related to the excluded volume of solvent molecules, which causes the chain statistics to be modified in the vicinity of other chains; this effect is important in strictly 2D systems.

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Graphical abstract Extended long chains at moderate density with solvent molecules inside coils.

     

Conformational analysis of α-d-Fuc-(1→4)-β-d-GlcNAc-OMe. One-dimensional transient NOE experiments and metropolis Monte Carlo simulations

Summary One-dimensional transient NOE build-up curves were measured for the synthetic disaccharide -d-Fuc-(14)--d-GlcNAc 1 utilizing Gaussian shaped pulses. Simulated build-up curves from Metropolis Monte Carlo simulations were compared to the experimental data. Disaccharide 1 is structurally related to methyl -d-maltoside in that it also contains an -(14) linkage, and it has the same configuration of groups around the glycosidic linkage. Analysis of NOEs in methyl -d-maltoside is restricted to those observed upon selective excitation of H1 because of severe spectral overlap. The situation is different in 1 where ¹H-NMR signals are well separated. Several interglycosidic NOEs were observed. The corresponding build-up curves allowed an accurate determination of the conformational preferences at the glycosidic linkage in 1. Comparison of experimental and theoretical NOE build-up curves showed clearly that rigid minimum-energy models cannot account for the experimental data. The best fit of experimental NOE build-up curves was obtained with theoretical curves from a 2×10⁶ step Metropolis Monte Carlo simulation with the temperature parameter set at 1000 K. Finally, it was observed that only the interglycosidic NOE H5/H6-pro-S significantly depends upon varying conformation distributions at the -(14)-glycosidic linkage, induced by choosing different temperature parameters for the Metropolis Monte Carlo simulations.     

Monte Carlo模拟肠道组织的非接触式漫反射光谱

本文采用Monte Carlo模拟人体肠道组织的非接触式漫反射光谱,并分别研究了聚焦光束的聚焦深度、组织表面入射光斑与出射光斑(Source-Detector,S-D)之间的距离、探测面积和探测深度对光谱测量的影响,为设计非接触式光谱检测系统提供理论依据。结果表明在利用光谱技术对肠道疾病如早期肠癌进行诊断时,非接触式光谱检测系统的聚焦深度应小于0.1 cm;在漫反射光谱检测时,应根据探测信号的强弱以及探测器的灵敏度选择S-D距离;0.06 cm的探测面积半径能有效地反映组织中氧合血红蛋白和脱氧合血红蛋白含量的变化情况;为反映不同深度组织光学特性,在改变探测深度时,应保持探测光锥顶角不变。     

Using a FRET Library with Multiple Probe Pairs To Drive Monte Carlo Simulations of α-Synuclein

We describe a strategy for experimentally-constraining computational simulations of intrinsically disordered proteins (IDPs), using α-synuclein, an IDP with a central role in Parkinson’s disease pathology, as an example. Previously, data from single-molecule Förster Resonance Energy Transfer (FRET) experiments have been effectively utilized to generate experimentally constrained computational models of IDPs. However, the fluorophores required for single-molecule FRET experiments are not amenable to the study of short-range (<30 Å) interactions. Using ensemble FRET measurements allows one to acquire data from probes with multiple distance ranges, which can be used to constrain Monte Carlo simulations in PyRosetta. To appropriately employ ensemble FRET data as constraints, we optimized the shape and weight of constraining potentials to afford ensembles of structures that are consistent with experimental data. We also used this approach to examine the structure of α-synuclein in the presence of the compacting osmolyte trimethylamine-N-oxide. Despite significant compaction imparted by 2 M trimethylamine-N-oxide, the underlying ensemble of α-synuclein remains largely disordered and capable of aggregation, also in agreement with experimental data. These proof-of-concept experiments demonstrate that our modeling protocol enables one to efficiently generate experimentally constrained models of IDPs that incorporate atomic-scale detail, allowing one to study an IDP under a variety of conditions.