Proton range monitoring with in-beam PET: Monte Carlo activity predictions and comparison with cyclotron data

GoalProton treatment monitoring with Positron-Emission-Tomography (PET) is based on comparing measured and Monte Carlo (MC) predicted β⁺ activity distributions. Here we present PET β⁺ activity data and MC predictions both during and after proton irradiation of homogeneous PMMA targets, where protons were extracted from a cyclotron.Methods and materialsPMMA phantoms were irradiated with 62 MeV protons extracted from the CATANA cyclotron. PET activity data were acquired with a 10 × 10 cm² planar PET system and compared with predictions from the FLUKA MC generator. We investigated which isotopes are produced and decay during irradiation, and compared them to the situation after irradiation. For various irradiation conditions we compared one-dimensional activity distributions of MC and data, focussing on Δw50%, i.e., the distance between the 50% rise and 50% fall-off position.ResultsThe PET system is able to acquire data during and after cyclotron irradiation. For PMMA phantoms the difference between the FLUKA MC prediction and our data in Δw50% is less than 1 mm. The ratio of PET activity events during and after irradiation is about 1 in both data and FLUKA, when equal time-frames are considered. Some differences are observed in profile shape.ConclusionWe found a good agreement in Δw50% and in the ratio between beam-on and beam-off activity between the PET data and the FLUKA MC predictions in all irradiation conditions.     

On the use of EBT3 film for relative dosimetry of kilovoltage X ray beams

EBT3 films were evaluated for relative dosimetry in water, in the energy range of therapeutic kV X ray beams. A film batch was calibrated in air for all nine beam qualities of a clinical unit (XStrahl 200). Monte Carlo (MC) simulations using MCNP v.6 facilitated the calculation of the film absorbed dose (f), and beam quality (k_bq) energy dependences in air. Results were found in agreement with corresponding data in the literature. Film samples from the same batch were irradiated in water along the central beam axis for each beam quality. Experimental percentage depth dose (PDD) results obtained using calibration data in air showed quality and depth dependent differences from corresponding MC simulations. These differences increased beyond film dosimetry uncertainty (<3.3%), reaching up to 8% at increased depth. The observed differences reduced only slightly when spectral variation as a function of measurement point was accounted for, using photon effective energy. PDD measurements and corresponding MC results facilitated the determination of f and k_bq in water. Results showed that the origin of the observed differences between experimental and MC PDD results is the difference between film response in air and water, as a result of radiation field perturbation from the film oriented along the central beam axis. This implies a directional dependence of film response which necessitates that the angular distribution of photons impinging on the film is the same in the calibration and measurement geometries.     

Technical note: GAMMORA,a free,open-source,and validated GATE-based model for Monte-Carlo simulations of the Varian TrueBeam

PurposeMonte Carlo (MC) is the reference computation method for medical physics. In radiotherapy, MC computations are necessary for some issues (such as assessing figures of merit, double checks, and dose conversions). A tool based on GATE is proposed to easily create full MC simulations of the Varian TrueBeam STx.MethodsGAMMORA is a package that contains photon phase spaces as a pre-trained generative adversarial network (GAN) and the TrueBeam’s full geometry. It allows users to easily create MC simulations for simple or complex radiotherapy plans such as VMAT. To validate the model, the characteristics of generated photons are first compared to those provided by Varian (IAEA format). Simulated data are also compared to measurements in water and heterogeneous media. Simulations of 8 SBRT plans are compared to measurements (in a phantom). Two examples of applications (a second check and interplay effect assessment) are presented.ResultsThe simulated photons generated by the GAN have the same characteristics (energy, position, and direction) as the IAEA data. Computed dose distributions of simple cases (in water) and complex plans delivered in a phantom are compared to measurements, and the Gamma index (3%/3mm) was always superior to 98%. The feasibility of both clinical applications is shown.ConclusionsThis model is now shared as a free and open-source tool that generates radiotherapy MC simulations. It has been validated and used for five years. Several applications can be envisaged for research and clinical purposes.     

Investigation of the halophilic PET hydrolase PET6 from Vibrio gazogenes

The handling of plastic waste and the associated ubiquitous occurrence of microplastic poses one of the biggest challenges of our time. Recent investigations of plastic degrading enzymes have opened new prospects for biological microplastic decomposition as well as recycling applications. For polyethylene terephthalate, in particular, several natural and engineered enzymes are known to have such promising properties. From a previous study that identified new PETase candidates by homology search, we chose the candidate PET6 from the globally distributed, halophilic organism Vibrio gazogenes for further investigation. By mapping the occurrence of Vibrios containing PET6 homologs we demonstrated their ubiquitous prevalence in the pangenome of several Vibrio strains. The biochemical characterization of PET6 showed that PET6 has a comparatively lower activity than other enzymes but also revealed a superior turnover at very high salt concentrations. The crystal structure of PET6 provides structural insights into this adaptation to saline environments. By grafting only a few beneficial mutations from other PET degrading enzymes onto PET6, we increased the activity up to three‐fold, demonstrating the evolutionary potential of the enzyme. MD simulations of the variant helped rationalize the mutational effects of those mutants and elucidate the interaction of the enzyme with a PET substrate. With tremendous amounts of plastic waste in the Ocean and the prevalence of Vibrio gazogenes in marine biofilms and estuarine marshes, our findings suggest that Vibrio and the PET6 enzyme are worthy subjects to study the PET degradation in marine environments.     

Monte Carlo GEANT4-based application for in vivo RBE study using small animals at LNS-INFN preclinical hadrontherapy facility

Preclinical studies represent an important step towards a deep understanding of the biological response to ionizing radiations. The effectiveness of proton therapy is higher than photons and, for clinical purposes, a fixed value of 1.1 is used for the relative biological effectiveness (RBE) of protons considered 1.1. Recent in vitro studies have reported that the RBE along the spread-out Bragg peak (SOBP) is not constant and, in particular, the RBE value increases on the distal part of SOBP. The present work has been carried-out in the perspective of a preclinical hadrontherapy facility at LNS-INFN and was focused on the experimental preparation of an in vivo study concerning the RBE variation along the SOBP. The main purpose of this work was to determine, using GEANT4-based Monte Carlo simulations, the best configuration for small animal treatments. The developed GEANT4 application simulates the proton-therapy beam line of LNS-INFN (CATANA facility) and allows to import the DICOM-CT images as targets. The RBE will be evaluated using a deterministic radiation damage like myelopathy as end-point. In fact, the dose at which the $50\%$ of animals will show the myelopathy is supposed to be LET-dependent. In this work, we studied different treatment configurations in order to choose the best two that maximize the LET difference reducing as much as possible the dose released to healthy tissue. The results will be useful to plan hadrontherapy treatments for preclinical in vivo studies and, in particular, for the future in vivo RBE studies.     

ANCA: Anharmonic Conformational Analysis of Biomolecular Simulations

Anharmonicity in time-dependent conformational fluctuations is noted to be a key feature of functional dynamics of biomolecules. Although anharmonic events are rare, long-timescale (μs–ms and beyond) simulations facilitate probing of such events. We have previously developed quasi-anharmonic analysis to resolve higher-order spatial correlations and characterize anharmonicity in biomolecular simulations. In this article, we have extended this toolbox to resolve higher-order temporal correlations and built a scalable Python package called anharmonic conformational analysis (ANCA). ANCA has modules to: 1) measure anharmonicity in the form of higher-order statistics and its variation as a function of time, 2) output a storyboard representation of the simulations to identify key anharmonic conformational events, and 3) identify putative anharmonic conformational substates and visualization of transitions between these substates.     

Cerenkov Luminescence Imaging (CLI) for Cancer Therapy Monitoring

In molecular imaging, positron emission tomography (PET) and optical imaging (OI) are two of the most important and thus most widely used modalities^1-3. PET is characterized by its excellent sensitivity and quantification ability while OI is notable for non-radiation, relative low cost, short scanning time, high throughput, and wide availability to basic researchers. However, both modalities have their shortcomings as well. PET suffers from poor spatial resolution and high cost, while OI is mostly limited to preclinical applications because of its limited tissue penetration along with prominent scattering optical signals through the thickness of living tissues.Recently a bridge between PET and OI has emerged with the discovery of Cerenkov Luminescence Imaging (CLI)^4-6. CLI is a new imaging modality that harnesses Cerenkov Radiation (CR) to image radionuclides with OI instruments. Russian Nobel laureate Alekseyevich Cerenkov and his colleagues originally discovered CR in 1934. It is a form of electromagnetic radiation emitted when a charged particle travels at a superluminal speed in a dielectric medium^7,8. The charged particle, whether positron or electron, perturbs the electromagnetic field of the medium by displacing the electrons in its atoms. After passing of the disruption photons are emitted as the displaced electrons return to the ground state. For instance, one ¹⁸F decay was estimated to produce an average of 3 photons in water⁵. Since its emergence, CLI has been investigated for its use in a variety of preclinical applications including in vivo tumor imaging, reporter gene imaging, radiotracer development, multimodality imaging, among others^4,5,9,10,11. The most important reason why CLI has enjoyed much success so far is that this new technology takes advantage of the low cost and wide availability of OI to image radionuclides, which used to be imaged only by more expensive and less available nuclear imaging modalities such as PET.Here, we present the method of using CLI to monitor cancer drug therapy. Our group has recently investigated this new application and validated its feasibility by a proof-of-concept study¹². We demonstrated that CLI and PET exhibited excellent correlations across different tumor xenografts and imaging probes. This is consistent with the overarching principle of CR that CLI essentially visualizes the same radionuclides as PET. We selected Bevacizumab (Avastin; Genentech/Roche) as our therapeutic agent because it is a well-known angiogenesis inhibitor^13,14. Maturation of this technology in the near future can be envisioned to have a significant impact on preclinical drug development, screening, as well as therapy monitoring of patients receiving treatments.     

The Parallel Worm Tracker: a platform for measuring average speed and drug-induced paralysis in nematodes

Background

Caenorhabditis elegans locomotion is a simple behavior that has been widely used to dissect genetic components of behavior, synaptic transmission, and muscle function. Many of the paradigms that have been created to study C. elegans locomotion rely on qualitative experimenter observation. Here we report the implementation of an automated tracking system developed to quantify the locomotion of multiple individual worms in parallel.

Methodology/Principal Findings

Our tracking system generates a consistent measurement of locomotion that allows direct comparison of results across experiments and experimenters and provides a standard method to share data between laboratories. The tracker utilizes a video camera attached to a zoom lens and a software package implemented in MATLAB®. We demonstrate several proof-of-principle applications for the tracker including measuring speed in the absence and presence of food and in the presence of serotonin. We further use the tracker to automatically quantify the time course of paralysis of worms exposed to aldicarb and levamisole and show that tracker performance compares favorably to data generated using a hand-scored metric.

Conclusions/Signficance

Although this is not the first automated tracking system developed to measure C. elegans locomotion, our tracking software package is freely available and provides a simple interface that includes tools for rapid data collection and analysis. By contrast with other tools, it is not dependent on a specific set of hardware. We propose that the tracker may be used for a broad range of additional worm locomotion applications including genetic and chemical screening.     

Experimental measurement and Monte Carlo assessment of Argon-41 production in a PET cyclotron facility

In a medical cyclotron facility, ⁴¹Ar (t_1/2 = 109.34 m) is produced by the activation of air due to the neutron flux during irradiation, according to the ⁴⁰Ar(n,γ)⁴¹Ar reaction; this is particularly relevant in widely diffused high beam current cyclotrons for the production of PET radionuclides. While theoretical estimations of the ⁴¹Ar production have been published, no data are available on direct experimental measurements for a biomedical cyclotron. In this work, we describe a sampling methodology and report the results of an extensive measurement campaign. Furthermore, the experimental results are compared with Monte Carlo simulations performed with the FLUKA code. To measure ⁴¹Ar activity, air samples were taken inside the cyclotron bunker in sealed Marinelli beakers, during the routine production of ¹⁸F with a 16.5 MeV GE-PETtrace cyclotron; this sampling thus reproduces a situation of absence of air changes. Samples analysis was performed in a gamma-ray spectrometry system equipped with HPGe detector. Monte Carlo assessment of the ⁴¹Ar saturation yield was performed directly using the standard FLUKA score RESNUCLE, and off-line by the convolution of neutron fluence with cross section data. The average ⁴¹Ar saturation yield per one liter of air of ⁴¹Ar, measured in gamma-ray spectrometry, resulted to be 3.0 ± 0.6 Bq/µA*dm³ while simulations gave a result of 6.9 ± 0.3 Bq/µA*dm³ in the direct assessment and 6.92 ± 0.22 Bq/µA*dm³ by the convolution neutron fluence-to-cross section.     

limma powers differential expression analyses for RNA-sequencing and microarray studies

limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.     

Dosimetric impacts of beam-hardening filter removal for the CyberKnife system

PurposeEquipment refurbishment was performed to remove the beam-hardening filter (BHF) from the CyberKnife system (CK). This study aimed to confirm the change in the beam characteristics between the conventional CK (present-BHF CK) and CK after the BHF was removed (absent-BHF CK) and evaluate the impact of BHF removal on the beam quality correction factors k_Q.MethodsThe experimental measurements of the beam characteristics of the present- and absent-BHF CKs were compared. The CKs were modeled using Monte Carlo simulations (MCs). The energy fluence spectra were calculated using MCs. Finally, k_Q were estimated by combining the MC results and analytic calculations based on the TRS-398 and TRS-483 approaches.ResultsAll gamma values for percent depth doses and beam profiles between each CK were less than 0.5 following the 3%/1 mm criteria. The percentage differences for tissue-phantom ratios at depths of 20 and 10 cm and percentage depth doses at 10 cm between each CK were −1.20% and −0.97%, respectively. The MC results demonstrated that the photon energy fluence spectrum of the absent-BHF CK was softer than that of the present-BHF CK. The k_Q values for the absent-BHF CK were in agreement within 0.02% with those for the present-BHF CK.ConclusionsThe photon energy fluence spectrum was softened by the removal of BHF. However, no remarkable impact was observed for the measured beam characteristics and k_Q. Therefore, the previous findings of the k_Q values for the present-BHF CK can be directly used for the absent-BHF CK.     

RASPA: molecular simulation software for adsorption and diffusion in flexible nanoporous materials

A new software package, RASPA, for simulating adsorption and diffusion of molecules in flexible nanoporous materials is presented. The code implements the latest state-of-the-art algorithms for molecular dynamics and Monte Carlo (MC) in various ensembles including symplectic/measure-preserving integrators, Ewald summation, configurational-bias MC, continuous fractional component MC, reactive MC and Baker's minimisation. We show example applications of RASPA in computing coexistence properties, adsorption isotherms for single and multiple components, self- and collective diffusivities, reaction systems and visualisation. The software is released under the GNU General Public License.     

In vivo imaging in NHP models of malaria: Challenges,progress and outlooks

Animal models of malaria, mainly mice, have made a large contribution to our knowledge of host–pathogen interactions and immune responses, and to drug and vaccine design. Non-human primate (NHP) models for malaria are admittedly under-used, although they are probably closer models than mice for human malaria; in particular, NHP models allow the use of human pathogens (Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium knowlesi). NHPs, whether natural hosts or experimentally challenged with a simian Plasmodium, can also serve as robust pre-clinical models. Some simian parasites are closely related to a human counterpart, with which they may share a common ancestor, and display similar major features with the human infection and pathology. NHP models allow longitudinal studies, from the early events following sporozoite inoculation to the later events, including analysis of organs and tissues, particularly liver, spleen, brain and bone marrow. NHP models have one other significant advantage over mouse models: NHPs are our closest relatives and thus their biology is very similar to ours.Recently developed in vivo imaging tools have provided insight into malaria parasite infection and disease in mouse models. One advantage of these tools is that they limit the need for invasive procedures, such as tissue biopsies. Many such technologies are now available for NHP studies and provide new opportunities for elucidating host/parasite interactions. The aim of this review is to bring the malaria community up to date on what is currently possible and what soon will be, in terms of in vivo imaging in NHP models of malaria, to consider the pros and the cons of the various techniques, and to identify challenges.     

Monte Carlo transport of swift protons and light ions in water: The influence of excitation cross sections,relativistic effects,and Auger electron emission in w-values

PurposeTo develop a particle transport code to compute w-values and stopping power of swift ions in liquid water and gases of interest for reference dosimetry in hadrontherapy. To analyze the relevance of inelastic and post-collisional processes considered.MethodsThe Monte Carlo code MDM was extended to the case of swift ion impact on liquid water (MDM-Ion). Relativistic corrections in the inelastic cross sections and the post-collisional Auger emission were considered. The effects of introducing different electronic excitation cross sections were also studied.ResultsThe stopping power of swift ions on liquid water, calculated with MDM-Ion, are in excellent agreement with recommended data. The w-values show a strong dependence on the electronic excitation cross sections and on the Auger electron emission. Comparisons with other Monte Carlo codes show the relevance of both the processes considered and of the cross sections employed. W and w-values for swift electron, proton, and carbon ions calculated with the MDM and MDM-Ion codes are in very close agreement with each other and with the 20.8 eV experimental value.ConclusionWe found that w-values in liquid water are independent of ion charge and energy, as assumed in reference dosimetry for hadrontherapy from sparse experimental results for electron and ion impact on gases. Excitation cross sections and Auger emission included in Monte Carlo codes are critical in w-values calculations. The computation of this physical parameter should be used as a benchmark for micro-dosimetry investigations, to assess the reliability of the cross sections employed.     

Multiple-source models for electron beams of a medical linear accelerator using BEAMDP computer code

AimThe aim of this work was to develop multiple-source models for electron beams of the NEPTUN 10PC medical linear accelerator using the BEAMDP computer code.BackgroundOne of the most accurate techniques of radiotherapy dose calculation is the Monte Carlo (MC) simulation of radiation transport, which requires detailed information of the beam in the form of a phase-space file. The computing time required to simulate the beam data and obtain phase-space files from a clinical accelerator is significant. Calculation of dose distributions using multiple-source models is an alternative method to phase-space data as direct input to the dose calculation system.Materials and methodsMonte Carlo simulation of accelerator head was done in which a record was kept of the particle phase-space regarding the details of the particle history. Multiple-source models were built from the phase-space files of Monte Carlo simulations. These simplified beam models were used to generate Monte Carlo dose calculations and to compare those calculations with phase-space data for electron beams.ResultsComparison of the measured and calculated dose distributions using the phase-space files and multiple-source models for three electron beam energies showed that the measured and calculated values match well each other throughout the curves.ConclusionIt was found that dose distributions calculated using both the multiple-source models and the phase-space data agree within 1.3%, demonstrating that the models can be used for dosimetry research purposes and dose calculations in radiotherapy.     

Assessment of the neutron dose field around a biomedical cyclotron: FLUKA simulation and experimental measurements

In the planning of a new cyclotron facility, an accurate knowledge of the radiation field around the accelerator is fundamental for the design of shielding, the protection of workers, the general public and the environment.Monte Carlo simulations can be very useful in this process, and their use is constantly increasing. However, few data have been published so far as regards the proper validation of Monte Carlo simulation against experimental measurements, particularly in the energy range of biomedical cyclotrons.In this work a detailed model of an existing installation of a GE PETtrace 16.5 MeV cyclotron was developed using FLUKA. An extensive measurement campaign of the neutron ambient dose equivalent H¹(10) in marked positions around the cyclotron was conducted using a neutron rem-counter probe and CR39 neutron detectors. Data from a previous measurement campaign performed by our group using TLDs were also re-evaluated.The FLUKA model was then validated by comparing the results of high-statistics simulations with experimental data. In 10 out of 12 measurement locations, FLUKA simulations were in agreement within uncertainties with all the three different sets of experimental data; in the remaining 2 positions, the agreement was with 2/3 of the measurements.Our work allows to quantitatively validate our FLUKA simulation setup and confirms that Monte Carlo technique can produce accurate results in the energy range of biomedical cyclotrons.     

DICOM-RT Ion interface to utilize MC simulations in routine clinical workflow for proton pencil beam radiotherapy

To adopt Monte Carlo (MC) simulations as an independent dose calculation method for proton pencil beam radiotherapy, an interface that converts the plan information in DICOM format into MC components such as geometries and beam source is a crucial element. For this purpose, a DICOM-RT Ion interface (https://github.com/topasmc/dicom-interface) has been developed and integrated into the TOPAS MC code to perform such conversions on-the-fly. DICOM-RT objects utilized in this interface include Ion Plan (RTIP), Ion Beams Treatment Record (RTIBTR), CT image, and Dose. Beamline geometries, gantry and patient coordinate systems, and fluence maps are determined from RTIP and/or RTIBTR. In this interface, DICOM information is processed and delivered to a MC engine in two steps. A MC model, which consists of beamline geometries and beam source, to represent a treatment machine is created by a DICOM parser of the interface. The complexities from different DICOM types, various beamline configurations and source models are handled in this step. Next, geometry information and beam source are transferred to TOPAS on-the-fly via the developed TOPAS extensions. This interface with two treatment machines was successfully deployed into our automated MC workflow which provides simulated dose and LET distributions in a patient or a water phantom automatically when a new plan is identified. The developed interface provides novel features such as handling multiple treatment systems based on different DICOM types, DICOM conversions on-the-fly, and flexible sampling methods that significantly reduce the burden of handling DICOM based plan or treatment record information for MC simulations.     

Influence of Microcrystal Formulation on In Vivo Absorption of Celecoxib in Rats

The objective of this study was to prepare celecoxib microcrystals using different stabilizers in order to evaluate the influence of microcrystal formulation on the in vitro dissolution rate and in vivo absorption after oral administration of celecoxib in rats. Three celecoxib microcrystals (MC1, MC2, and MC3) were prepared using solvent change method. Microcrystals were evaluated for morphology, particle size, crystallinity, solubility, in vitro dissolution, and in vivo absorption in rats. Scanning electron microscopy images showed distinct differences in the morphologies and dimensions of various celecoxib microcrystals. The particle size of all microcrystals was significantly (P < 0.05) reduced relative to plain celecoxib. The DSC and XRD results revealed that MC1 retain drug crystallinity relative to control crystals, MC2, and MC3. All microcrystals showed marked increase in the drug dissolution parameters particularly MC1 that exhibited a prompt drug release and significantly (P < 0.05) higher values of % dissolution efficiency as compared to control celecoxib and the other microcrystals. The influence of microcrystals on the in vivo absorption of celecoxib was studied in rats in comparison to plain drug. The results of in vivo absorption study in rats indicated that MC1 significantly improved the rate and extent of celecoxib absorption than plain celecoxib. The mean relative bioavailability of MC1 formulation to plain celecoxib was 157.55 ± 20.18%. In conclusion, microcrystal formulation of celecoxib results not only in an enhancement of dissolution parameters but also improves the bioavailability of celecoxib in rats.KEY WORDS: celecoxib, dissolution, in vivo absorption, microcrystals, particle size     

The use of non-standard CT conversion ramps for Monte Carlo verification of 6 MV prostate IMRT plans

Monte Carlo (MC) dose calculation algorithms have been widely used to verify the accuracy of intensity-modulated radiotherapy (IMRT) dose distributions computed by conventional algorithms due to the ability to precisely account for the effects of tissue inhomogeneities and multileaf collimator characteristics. Both algorithms present, however, a particular difference in terms of dose calculation and report. Whereas dose from conventional methods is traditionally computed and reported as the water-equivalent dose (D_w), MC dose algorithms calculate and report dose to medium (D_m). In order to compare consistently both methods, the conversion of MC D_m into D_w is therefore necessary.This study aims to assess the effect of applying the conversion of MC-based D_m distributions to D_w for prostate IMRT plans generated for 6 MV photon beams. MC phantoms were created from the patient CT images using three different ramps to convert CT numbers into material and mass density: a conventional four material ramp (CTCREATE) and two simplified CT conversion ramps: (1) air and water with variable densities and (2) air and water with unit density. MC simulations were performed using the BEAMnrc code for the treatment head simulation and the DOSXYZnrc code for the patient dose calculation. The conversion of D_m to D_w by scaling with the stopping power ratios of water to medium was also performed in a post-MC calculation process.The comparison of MC dose distributions calculated in conventional and simplified (water with variable densities) phantoms showed that the effect of material composition on dose-volume histograms (DVH) was less than 1% for soft tissue and about 2.5% near and inside bone structures. The effect of material density on DVH was less than 1% for all tissues through the comparison of MC distributions performed in the two simplified phantoms considering water. Additionally, MC dose distributions were compared with the predictions from an Eclipse treatment planning system (TPS), which employed a pencil beam convolution (PBC) algorithm with Modified Batho Power Law heterogeneity correction. Eclipse PBC and MC calculations (conventional and simplified phantoms) agreed well (<1%) for soft tissues. For femoral heads, differences up to 3% were observed between the DVH for Eclipse PBC and MC calculated in conventional phantoms. The use of the CT conversion ramp of water with variable densities for MC simulations showed no dose discrepancies (0.5%) with the PBC algorithm. Moreover, converting D_m to D_w using mass stopping power ratios resulted in a significant shift (up to 6%) in the DVH for the femoral heads compared to the Eclipse PBC one.Our results show that, for prostate IMRT plans delivered with 6 MV photon beams, no conversion of MC dose from medium to water using stopping power ratio is needed. In contrast, MC dose calculations using water with variable density may be a simple way to solve the problem found using the dose conversion method based on the stopping power ratio.