Preparation and characterization of a radiobiology beam-line at the 18 MeV proton cyclotron facility at CNA

Trabajo presentado en el II Workshop Español de Protonterapia, celebrado en Sevilla (España), del 15 al 18 de marzo de 2018Peer reviewe

Parameterising microdosimetric distributions of mono-energetic proton beams for fast estimates of yD and y∗

Wepresent analytical models of the dose-mean lineal energy (yD) and the saturation-corrected dosemean lineal energy (y∗) for fast and accurate radiobiological calculations in proton therapy. These models are based on the modelling of microdosimetric distributions f(ϵs) obtained from Monte Carlo (MC) simulations of the energy deposited per interaction event, ϵs, for mono-energetic proton beams in water with an energy range from 0.6 MeV to 95 MeV.Wealso performed calculations of Relative Biological Effectiveness (RBE) based on both,MCand the analytical models of y∗, using the Microdosimetric Kinetic Model (MKM) for Human Salivary Gland (HSG) cells. Both RBE calculations were then compared to demonstrate the consistency of the agreement between the microdosimetric distributions themselves as well as of any other distributions based on them. Maximum, mininum and average relative differences betweenMCand analytical values were reported as well as paired Student t-tests to display the goodness of our tool to model y, D y∗ and RBE distributions. For yD values the maximum, minimum and average relative discrepancies were 0.99%, ?1.67% and?0.06% respectively. In the case of y∗ values these differences were 0.98%,?1.55% and ?0.07%, while for RBE values they were 0.37%,?0.75% and?0.04% respectively. The Student t-tests showed that no statistically significant differences were observed betweenMCand analytical values. Our analytical tool has provided instantaneous calculations of the magnitudes of interest, in contrast with the computation times required withMCsimulations.Wehave developed an algorithm which provides fast calculations of yD and y∗, maintaining a clinically relevant accuracy level

Microdosimetry-based dose-averaged linear energy transfer calculation for clinical proton beams: a Monte Carlo study with Geant4-DNA

Trabajo presentado en el 3rd Geant4 International User Conference at the Physics, Medicine, Biology frontier, celebrado en Bordeaux (Francia), del 29 al 31 de octubre de 2018This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 675265, OMA – Optimization of Medical Accelerators, and from the Spanish Ministry of Economy and Competitiveness under grant No FPA2016- 77689-C2-1-R. The Monte Carlo simulations were carried out at the FIS-ATOM cluster hosted at CICA (Seville, Spain).Peer reviewe

Dosimetry with gafchromic films based on a new micro-opto-electro-mechanical system

This work presents the first tests performed with radiochromic films and a new Micro‒Opto‒Electro-Mechanical system (MOEMS) for in situ dosimetry evaluation in radiotherapy in real time. We present a new device and methodology that overcomes the traditional limitation of time-delay in radiochromic film analysis by turning a passive detector into an active sensor. The proposed system consists mainly of an optical sensor based on light emitting diodes and photodetectors controlled by both customized electronic circuit and graphical user interface, which enables optical measurements directly. We show the first trials performed in a low‒energy proton cyclotron with this MOEMS by using gafchromic EBT3 films. Results show the feasibility of using this system for in situ dose evaluations. Further adaptation is ongoing to develop a full real‒time active detector by integrating MOEM multi‒arrays and films in flexible printed circuits. Hence, we point to improve the clinical application of radiochromic films with the aim to optimize radiotherapy treatment verifications

Limitations of solid-state devices for microdosimetry applications

Trabajo presentado en el 3rd International Conference on Dosimetry and its Applications, celebrado en Lisboa, del del 27 al 31 de mayo de 2019[Introduction] Use of solid-state sensors for measuring microdosimetric quantities has been increasing recently due to advantages such as its size, portability and its lack of high voltage biasing to work properly. However, these devices do not lack drawbacks; drift and diffusion phenomena affect partial charge collection, modifying the microdosimetric spectra depending on the geometry of the site, operation conditions and readout electronic noise. [Methods] Drift and diffusion processes are very relevant when micrometric active sites are considered. A perturbation in the pulse height detected spectrum respect to the ideal imparted energy within the considered site geometry is produced. Effects in silicon micro-dosimeters built by IMB-INM (CSIC, Spain) were evaluated. To parametrize the charge collection effi ciency an IBIC test at CNA (Seville, Spain) was performed and results were compared with TCAD simulations. The device model used together with FLUKA Monte Carlo simulations has been compared with experimental micro-dosimetric spectra of a clinical 12C ion beam at Fondazione CNAO (Pavia, Italy). [Results] Smeared Monte Carlo spectra reproduce the main features of the experimental spectra taken with the silicon microdosimeters affected by partial charge collection events. The perturbation on the frequency and dose averaged lineal energy as a function of micro-dosimeter size was evaluated. Additionally, the minimum detectable lineal energy for no intrinsic gain devices was evaluated considering a general model of readout electronics as a function of the fl uence averaged mass thickness of solid-state micro-dosimeters. [Conclusions] Solid-state devices can be employed to measure microdosimetric spectra, but large collection and electronic noise pose limitations on their performance. The perturbation on the microdosimetric spectra has been evaluated in this work to set a general benchmark for the expected performance of a micro-dosimeter depending on geometry and sensitive media.Peer reviewe

Feasibility study of a proton irradiation facility for fadiobiological measurements at an 18 MeV Cyclotron

A feasibility study of an experimental setup for the irradiation of biological samples at the cyclotron facility installed at the National Centre of Accelerators (Seville, Spain) is presented. This cyclotron, which counts on an external beam line for interdisciplinary research purposes, produces an 18 MeV proton beam, which is suitable for the irradiation of mono-layer cultures for the measurement of proton cell damages and Relative Biological Effectiveness (RBE) at energies below the beam nominal value. Measurements of this kind are of interest for proton therapy, since the variation of proton RBE at the distal edge of the Bragg curve may have implications in clinical proton therapy treatments. In the following, the characteristics of the beam line and the solutions implemented for the irradiation of biological samples are described. When dealing with the irradiation of cell cultures, low beam intensities and broad homogeneous irradiation fields are required, in order to assure that all the cells receive the same dose with a suitable dose rate. At the cyclotron, these constraints have been achieved by completely defocusing the beam, intercepting the beam path with tungsten scattering foils and varying the exit-window-to-sample distance. The properties of the proton beam thus obtained have been analysed and compared with Monte Carlo simulations. The results of this comparison, as well as the experimental measurement of the lateral dose profiles expected at the position of samples are presented. Meaningful dose rates of about 2–3 Gy/min have been obtained. Homogeneous lateral dose profiles, with maximum deviations of 5%, have been measured at a distance of approximately 50 cm in air from the exit window, placing a tungsten scattering foil of 200 µm in the beam path.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant No. 675265, OMA—Optimization of Medical Accelerators, from the Spanish Ministry of Economy and Competitiveness under Grant No. FPA2016-77689-C2-1-R, and from the Council for Innovation, Science and Commerce of the Andalusian Government under Grant No. P12-FQM-1605.Peer reviewe

Proton RBE at low energies: preparation of a new radiobiology beam line at the 18 MeV proton cyclotron facility at CNA

Trabajo presentado en las II Jornadas RSEF / IFIMED de Física Médica, celebradas en Madrid (España), del 14 al 15 de junio de 2018In the last decades, proton therapy has gained great interest in the medical community thanks to its excellent clinical results. The bases of this success are: (1) the physical advantages of protons with respect to conventional radiation therapy with photons, due to their more selective energy deposition in depth; and (2) their increased radiobiological effectiveness as compared with photon radiotherapy for a same level of absorbed dose, property usually referred to as Relative Biological Effectiveness or RBE. Even if it is agreed that proton RBE varies towards the distal Bragg peak region, increasing with LET, nowadays in clinical proton therapy treatments, a uniform RBE value of 1.1 is generally used. Therefore, studies of RBE at low proton energies are necessary in order to reach a consensus on the RBE variations near the Bragg peak, which could be significant in the optimization of proton therapy treatment plans. With the purpose of providing a monochromatic beam for RBE measurements at low energies (below 18 MeV in our case), we are preparing an experimental setup at the external beam line of the 18MeV proton cyclotron facility installed at the CNA (Seville, Spain). In this work, we present our first feasibility studies. Two are the main constraints when dealing with the irradiation of biological samples in our setup: low beam intensity, of the order of some pA, to control properly the fluence during irradiation time, and broad irradiation field, of the order of 3cm side, uniform in both energy and space. To improve the homogeneity and decrease the beam intensity, we have decided to use a completely defocused beam and to scatter the beam downstream the exit window, both placing tungsten foils of different thicknesses and changing the amount of air between the window and the position of the samples. So far, we have measured the properties of wide beams produced with tungsten scattering foils of various thicknesses. With a 150 m thick tungsten foil, we could produce a 10 MeV proton beam with almost homogeneous intensity, having deviations of the order of ~10% in the central 35 mm and at ~50 cm distance from the exit window. Furthermore, we have performed preliminary dosimetric studies, using EBT3 radiochromic films and a transmission ionization chamber for dose and proton fluence evaluation. Studies of this nature are of great interest, since radiochromic films would be a handy and easy to use dosimeter solution for proton RBE studies. Finally, we are developing with the Geant4 toolkit a Monte Carlo tool, which reproduces accurately the cyclotron beam properties with the aim of simulating future improvements proposed on the final optimization of the setup for the irradiation of biological samples.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 675265, OMA - Optimization of Medical Accelerators, and from the Spanish Ministry of Economy and Competitiveness under grant No FPA2016-77689-C2-1-R. The Monte Carlo simulations were carried out at the FIS-ATOM cluster hosted at CICA (Seville, Spain).Peer reviewe

Geant4 simulation and validation of the CNA cyclotron beam parameters

Trabajo presentado en el 3rd OMA Topical Workshop on Accelerator Design and Diagnostics, celebrado en Darmstadt (Alemania), del 11 al 18 de diciembre de 2018Peer reviewe

Development of a radiobiology beam line at the 18 MeV proton cyclotron facility at CNA

Trabajo presentado en 2nd OMA Topical Workshop on Diagnostics for Beam and Patient Monitoring, celebrado en Ginebra (Suiza), del 4 al 5 de junio de 2018Peer reviewe

Malfunction of cardiac devices after radiotherapy without direct exposure to ionizing radiation: Mechanisms and experimental data

AIMS: Malfunctions of cardiac implantable electronical devices (CIED) have been described after high-energy radiation therapy even in the absence of direct exposure to ionizing radiation, due to diffusion of neutrons (n) causing soft errors in inner circuits. The purpose of the study was to analyse the effect of scattered radiation on different types and models of CIED and the possible sources of malfunctions. METHODS AND RESULTS: Fifty-nine explanted CIED were placed on an anthropomorphous phantom of tissue-equivalent material, and a high-energy photon (15 MV) radiotherapy course (total dose = 70 Gy) for prostate treatment was performed. All devices were interrogated before and after radiation. Radiation dose, the electromagnetic field, and neutron fluence at the CIED site were measured. Thirty-four pacemakers (PM) and 25 implantable cardioverter-defibrillators (ICD) were analysed. No malfunctions were detected before radiation. After radiation a software malfunction was evident in 13 (52%) ICD and 6 (18%) PM; no significant electromagnetic field or photon radiations were detected in the thoracic region. Neutron capture was demonstrated by the presence of the (198)Au((197)Au + n) or (192)Ir((191)Ir + n) isotope activation; it was significantly greater in ICD than in PM and non-significantly greater in damaged devices. A greater effect in St Jude PM (2/2 damaged), Boston (9/11), and St Jude ICD (3/6) and in older ICD models was observed; the year of production was not relevant in PM. CONCLUSION: High-energy radiation can cause different malfunctions on CIED, particularly ICD, even without direct exposure to ionizing radiation due to scattered radiation of neutrons produced by the linear accelerator