. The Monte Carlo simulation software is a valuable tool in radiation therapy, in particular to achieve the needed accuracy in the dose evaluation for the treatment plans optimisation. The current ...challenge in this field is the time reduction to open the way to many clinical applications for which the computational time is an issue. In this manuscript we present an innovative GPU-accelerated Monte Carlo software for dose valuation in electron and photon based radiotherapy, developed as an update of the FRED (Fast paRticle thErapy Dose evaluator) software.
. The code transports particles through a 3D voxel grid, while scoring their energy deposition along their trajectory. The models of electromagnetic interactions in the energy region between 1 MeV-1 GeV available in literature have been implemented to efficiently run on GPUs, allowing to combine a fast tracking while keeping high accuracy in dose assessment. The FRED software has been bench-marked against state-of-art full MC (FLUKA, GEANT4) in the realm of two different radiotherapy applications: Intra-Operative Radio Therapy and Very High Electron Energy radiotherapy applications.
. The single pencil beam dose-depth profiles in water as well as the dose map computed on non-homogeneous phantom agree with full-MCs at 2% level, observing a gain in processing time from 200 to 5000.
. Such performance allows for computing a plan with electron beams in few minutes with an accuracy of ∼%, demonstrating the FRED potential to be adopted for fast plan re-calculation in photon or electron radiotherapy applications.
In the framework of the euro SIG project and within an international collaboration between CNAO, CERN, INFN, and MedAustron, the design of a novel gantry for hadron therapy based on superconducting ...magnets and a downstream scanning system has been undertaken. The choice of placing the scanning system downstream of the last superconducting dipole plays a crucial role in the overall layout of the gantry, having a direct impact on its radius, weight, and cost. The proposed design for the scanning system considers two separate normal-conducting scanning magnets with a central field in the order of 1 T, three times higher than the current state-of-the-art scanning magnets for hadron therapy. Such a magnetic field value for a fast-pulsed magnet poses interesting questions regarding non-linearities due to the yoke saturation, hysteretic effects, and eddy currents. In this context, it is important to develop reliable models to study the behavior of the magnet at various levels of current and magnetic field. For this reason, we implemented two and three-dimensional simulations of a short dipole with FeCo yoke and we validated them against experimental measurements. In this paper, we focus on the modelization of the hysteretic behavior of this magnet, providing insight into the feasibility of proposed scanning magnets.
Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this ...technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms.
The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account.
The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far.
•A fast GPU based MC has been developed for IOeRT breast treatment planning.•The input is an ultrasound image with defined PTV and OARs.•Different applicator positions, dimensions and angles and beam energies are tested.•Plan is optimised using absorbed dose maps and related DVHs.•Results in the context of conventional and FLASH irradiations are discussed.
The treatment of deep-seated tumours with electrons of very high energies (VHEE, 70–150 MeV) has already been explored in the past, suggesting that a dosimetric coverage comparable with ...state-of-the-art proton (PT) or photon radiotherapy (RT) could be achieved with a large (
>
10) number of fields and high electron energy. The technical and economical challenges posed by the deployment of such beams in treatment centres, together with the expected small therapeutic gain, prevented the development of such technique. This scenario could radically change in the light of recent developments that occurred in the compact, high-gradient, electron acceleration technology and, additionally, of the experimental evidence of the sparing of organs at risk achieved in ultra-high dose rate irradiation, also referred to as FLASH. Electrons with the energy required to treat intracranial lesions could be provided, at dose rates compatible with what is needed to trigger the FLASH effect, by accelerators that are a few metres long, and the organ sparing could be exploited to significantly simplify the irradiation geometry, decreasing the number of fields needed to treat a patient. In this paper, the case of two patients affected by a chordoma and a meningioma, respectively, treated with protons in Trento (IT) is presented. The proton plans have been compared with VHEE plans and X-ray intensity-modulated radiotherapy (IMRT) plans. The VHEE plans were first evaluated in terms of physical dose distribution and then assuming that the FLASH regimen can be achieved. VHEE beams demonstrated their potential in obtaining plans that have comparable tumour coverage and organs at risk sparing when benchmarked against current state-of-the-art IMRT and PT. These results were obtained with a number of explored fields that was in the range between 3 and 7, consistent with what is routinely performed in IMRT and PT conventional irradiations. The FLASH regimen, in all cases, showed its potential in reducing damage to the organs placed nearby the target volume, allowing, particularly in the chordoma case where the irradiation geometry is more challenging, a better tumour coverage with respect to the conventional treatments.
Purpose: Intraoperative electron radiotherapy (IOeRT) is considered the first clinical translation of FLASH with electrons. A crucial aspect is represented by the precise dose monitoring and ...measurement; to this aim, we propose a method fully based on Monte Carlo (MC) simulation that uses as input the beam current measurement and the beam optics simulation. To validate this approach, we chose the NOVAC11 (produced by Sordina IORT Technologies SpA) accelerator, which provides a well-studied model. Methods: We used FLUKA and FRED MC software to simulate in detail the geometry of the NOVAC11 and the coupled applicator usually adopted in clinical practice to deliver the dose in the surgical bed. The simulation results of the longitudinal and off-axis profiles and dose per pulse obtained in a water phantom with different applicators are compared to the experimental data. Results: A very good agreement not only for the relative dosimetry in both the longitudinal and off-axis profiles, with a gamma index pass rate of 100% with 3%/3 mm acceptance criteria, but also for the absolute dosimetry was obtained. Conclusion: The results completely validate the MC description of the system and provide a reliable evaluation of the dose per pulse and output factor with an accuracy of the order of few % for different sets of applicator diameters and lengths.
Sepsis is initiated by interactions between microbial products and host inflammatory cells. Toll-like receptors (TLRs) are central innate immune mediators of sepsis that recognize different ...components of microorganisms. Peptidoglycan-associated lipoprotein (PAL) is a ubiquitous gram-negative bacterial outer-membrane protein that is shed by bacteria into the circulation of septic animals. We explored the inflammatory effects of purified PAL and of a naturally occurring form of PAL that is shed into serum. PAL is released into human serum by Escherichia coli bacteria in a form that induces cytokine production by macrophages and is tightly associated with lipopolysaccharide (LPS). PAL activates inflammation through TLR2. PAL and LPS synergistically activate macrophages. These data suggest that PAL may play an important role in the pathogenesis of sepsis and imply that physiologically relevant PAL and LPS are shed into serum and act in concert to initiate inflammation in sepsis
Introduction: Charged Particle Therapy plays a key role in the treatment of deep-seated tumours, because of the advantageous energy deposition culminating in the Bragg peak. However, knowledge of the ...dose delivered in the entrance channel is limited by the lack of data on the beam and fragmentation of the target. Methods: The FOOT experiment has been designed to measure the cross sections of the nuclear fragmentation of projectile and target with two different detectors: an electronic setup for the identification of Z ≥ 3 fragments and a nuclear emulsion spectrometer for Z ≤ 3 fragments. In this paper, we analyze the data taken by exposing four nuclear emulsion spectrometers, with C and C 2 H 4 targets, to 200 MeV/n and 400 MeV/n oxygen beams at GSI Helmholtzzentrum für Schwerionenforschung (Darmstadt, Germany), and we report the charge identification of produced fragments based on the controlled fading induced on nuclear emulsion films. Results: The goal of identifying fragments as heavy as lithium has been achieved. Discussion: The results will contribute to a better understanding of the nuclear fragmentation process in charged particle therapy and have implications for refining treatment planning in the presence of deep-seated tumors.
Despite frequent herpes simplex virus (HSV) reactivation, peripheral nerve destruction and sensory anesthesia are rare. We discovered that skin biopsies obtained during asymptomatic human HSV-2 ...reactivation exhibit a higher density of nerve fibers relative to biopsies during virological and clinical quiescence. We evaluated the effects of HSV infection on keratinocytes, the initial target of HSV replication, to better understand this observation. Keratinocytes produced IL-17c during HSV-2 reactivation, and IL-17RE, an IL-17c-specific receptor, was expressed on nerve fibers in human skin and sensory neurons in dorsal root ganglia. In ex vivo experiments, exogenous human IL-17c provided directional guidance and promoted neurite growth and branching in microfluidic devices. Exogenous murine IL-17c pretreatment reduced apoptosis in HSV-2-infected primary neurons. These results suggest that IL-17c is a neurotrophic cytokine that protects peripheral nerve systems during HSV reactivation. This mechanism could explain the lack of nerve damage from recurrent HSV infection and may provide insight to understanding and treating sensory peripheral neuropathies.
•Kinetic Monte Carlo modeling with distributed species requires the appropriate search method.•Performance testing for linear, tree-based, q-section, (hybrid) interpolation and search methods.•The ...search method needs to be selected based on the system size.•Comparison of execution times, search/modification times and number of iterations.
Monte Carlo modeling has emerged as a powerful tool to describe system state variations in many engineering systems. If distributed species are involved, the so-called Gillespie-based kinetic Monte Carlo (kMC) simulations are very promising, provided that the search method to identify individual population members is properly chosen. A comparative study is therefore performed on the most promising search methods, using the stochastic simulation algorithm and considering system size variations from 102 to 106 employing 107 randomly selected targets. Attention is paid to already applied search methods as well as novel ones based on recent insights. It is demonstrated that for smaller systems the execution time of the linear search method is the lowest, and for larger systems the quaternary tree-based and tetrasection search methods are most suited. The tests are interpreted based on the search/modification times and an analysis based on iteration numbers is addressed.
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