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

Feasibility Study of a Proton Irradiation Facility for Radiobiological 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

Development of an external beam line for radiobiology experiments and microdosimetry applications at the 18 MeV proton cyclotron facility at CNA

Cancer is one of the leading causes of mortality world-wide, killing more than one million people per year just in Europe. Nowadays, proton therapy is one of the most promising techniques in the fight against cancer, being two the main bases of its success: (1) the physical advantages of protons with respect to conventional radiotherapy with photons, resulting in a more selective energy deposition in depth; (2) the increased biological effectiveness of protons with respect to photons and their denser pattern of energy deposition in matter, usually determining a more lethal damage to the DNA. The biological effect of protons and other ions with respect to photons is described in terms of the Relative Biological Effectiveness (RBE), i.e., the ratio between the doses of the reference and studied radiation determining the same effect. In clinical proton therapy, a RBE value of 1.1 is currently used. However, there is an increasing awareness that proton RBE is not a constant, but seems to increase linearly with the Linear Energy Transfer (LD) of the proton as it slows down in tissues, especially close to the distal region of the Bragg peak, possibly leading to toxicity in healthy tissue beyond the target. In this context, recent studies aim at including dose-averaged LET objective functions in treatment planning optimization to take full advantage of the increased RBE in protons beams. This last problem, and the characterisation of RBE, can be addressed with the formalism of microdosimetry, which, on one hand, permits the calculation of RBE from a microscopic approach by means of the microdosimetric kinetic model (MKM) and, on the other hand, provides physical concepts and computational tools to calculate macroscopic LD distributions. The rationale behind this thesis project is, therefore, given by the necessity of performing studies of proton RBE at low energies, close to the Bragg peak region of clinical proton beams (below 40MeV), which would help reaching a consensus on the variation of proton RBE with LET. To do so, two main objectives were foreseen: (1) the design and mounting of a low energy proton facility at CNA (proton kinetic energy below 18MeV) for the experimental study of RBE in mono-layer cell cultures and (2) the development of a simulation tool to study the patterns of energy deposition of protons in water at a micrometric scale, for the computation of microdosimetric quantities. This thesis is divided in four chapters. In Chapter 1, the physics foundations of proton therapy are presented, followed by a description of the relevant biological parameters. In this context, special attention is given to the formalisms of microdosimetry and its most relevant quantities. Then, an insight into Monte Carlo simulations and the main codes used in this work is presented, together with a description of the radiation dosimeters employed for the experimental measurements performed. Chapter 2 is dedicated to the description of the radiobiology beam line designed and mounted at the 18MeV proton cyclotron facility installed at the National Centre of Accelerators (CNA, Seville, Spain), focusing especially on the overall optimization of the beam parameters to define the best setup for the irradiation of mono-layer cell cultures. In this chapter, a Monte Carlo simulation of the beam line, realised with Geant4 and validated towards experimental measurements, is also presented. In Chapter 3 a Monte Carlo track structure application, which was developed for the computation of microdosimetric distributions of protons in liquid water, is described. This application, based on Geant4-DNA, provides two sampling methods, uniform and weighted, for the scoring of the quantities of interest in spherical sites. Furthermore, it is used to verify the validity range of a formula that links microdosimetric quantities to the macroscopic dose-averaged LET distribution, being a powerful tool for the development of analytical models to be used in treatment planning optimisation. Chapter 4 presents the results of the first irradiation of cell cultures at the radiobiology beam line developed at the cyclotron facility. In this context, an application of the Monte Carlo code for the computation of microdosimetric quantities is shown. With this code, a theoretical derivation of the expected RBE for the experimental irradiation and cells under study could be done, through the use of the microdosimetric kinetic model. Finally, a summary of the results obtained and a brief discussion on the future perspectives of this project conclude this work

Segment-averaged LET concept and analytical calculation from microdosimetric quantities in proton radiation therapy

Purpose: This work introduces the concept of segment-averaged linear energy transfer (LET) as a new approach to average distributions of LET of proton beams based on a revisiting of microdosimetry theory. The concept of segment-averaged LET is then used to generate an analytical model from Monte Carlo simulations data to perform fast and accurate calculations of LET distributions for proton beams and material: The distribution of energy imparted by a proton beam into a representative biological structure or site is influenced by the distributions of (1) LET, (2) segment length, which is the section of the proton track in the site, and (3) energy straggling of the proton beam. The distribution of LET is thus generated by the LET of each component of the beam in the site. However, the situation when the LET of each single proton varies appreciably along its path in the site is not defined. Therefore, a new distribution can be obtained if the particle track segment is decomposed into smaller portions in which LET is roughly constant. We have called “segment distribution” of LET the one generated by the contribution of each portion. The average of that distribution is called segment-averaged LET. This quantity is obtained in the microdosimetry theory from the average and standard deviation of the distributions of energy imparted to the site, segment length and energy imparted per collision. All this information is calculated for protons of clinically relevant energies by means of Geant4-DNA microdosimetric simulations. Finally, a set of analytical functions is proposed for each one of the previous quantities. The presented model functions are fitted to data from Geant4-DNA simulations for monoenergetic beams from 100 keV to 100 MeV and for spherical sites of 1 μm, 5 μm and 10 μm in diameter. Results: The average differences along the considered energy range between calculations based on our analytical models and MC for segment-averaged dose-averaged restricted LET are -0.2 ± 0.7 keV/μm for the 1 μm case, 0.0 ± 0.9 keV/μm for the 5 μm case and -0.3 ± 1.1 keV/μm for the 10 μm case, respectively. All average differences are below the average standard deviation (1σ) of the MC calculations. Conclusions: A new way of averaging LET for a proton beam is performed to incorporate the effects produced by the variation of stopping power of each individual proton along microscopic biological structures. An analytical model based on MC simulations allows for fast and accurate calculations of segment-averaged dose-averaged restricted LET for proton beams, which otherwise would need to be calculated from exhaustive MC simulations of clinical plans.Spanish Ministry of Economy and Competitiveness under Grant No. FPA2016-77689-C2-1-

NuTag: proof-of-concept study for a long-baseline neutrino beam

International audienceThe study of neutrino oscillation at accelerators is limited by systematic uncertainties, in particular on the neutrino flux, cross-section, and energy estimates. These systematic uncertainties could be eliminated by a novel experimental technique: neutrino tagging. This technique relies on a new type of neutrino beamline and its associated instrumentation which would enable the kinematical reconstruction of the neutrinos produced in $\pi^{\pm} \to \mu^{\pm} \nu_\mu$ and $K^{\pm} \to \mu^{\pm} \nu_\mu$ decays. This article presents a proof-of-concept study for such a tagged beamline, aiming to serve a long baseline neutrino experiment exploiting a megaton scale natural water Cherenkov detector. After optimizing the target and the beamline optics to first order, a complete Monte Carlo simulation of the beamline has been performed. The results show that the beamline provides a meson beam compatible with the operation of the spectrometer, and delivers a neutrino flux sufficient to collect neutrino samples with a size comparable with similar experiments and with other un-tagged long-baseline neutrino experimental proposals

Impact of charge collection efficency and electronic noise on the performance of solid state 3D-microdetectors

International audienceMicrodosimetry has been traditionally performed through gaseous proportional counters, although in recent years different solid state microdosimeters have been proposed and constructed for this task. In this paper we analyze the response of solid state devices of micrometric size with no intrinsic gain developed by CNM-CSIC (Spain). There are two major aspects of the operation of these devices that affect the reconstruction of the probability distributions and momenta of stochastic quantities related to microdosimetry. For micrometric volumes the drift and diffusion of the charge carriers gives rise to a partial charge collection efficiency in the peripheral region of the depleted volume. Such effect produce a perturbation of the reconstructed pulse height (i.e. imparted energy) distributions with respect to the actual microdosimetric distributions. The relevance of this deviation depends on the size, geometry and operation conditions of the device. On the other hand, the electronic noise from the single event readout setup poses a limit on the minimum detectable lineal energy when the microdosimeter size is reduced. This article addresses these issues to provide a framework on the physical constraints for the design and operation of solid state microdosimeters