A miniaturized alpha spectrometer for the calibration of an avalanche-confinement TEPC

The design and development of a recent avalanche-confinement tissue equivalent proportional counter (TEPC) for microdosimetry and nanodosimetry applications required the selection of a proper miniaturized solid state detector (SSD) for detecting alpha particles emitted by a thick removable Cm-244 source embedded in the cylindrical TEPC chamber for characterization and calibration purposes. Since the available cavity for embedding the SSD detector is only 4.2 mm in diameter, no standard devices can be exploited. The selection of the best SSD for this application was based on the following requirements: very low size, proper energy resolution, cheapness. The performances of the finally selected SSD were assessed by exploiting a multi-peak calibration alpha source (Pu-239, Am-241, Cm-244). The measured energy resolution resulted about 25 keV FWHM. The TEPC calibration procedure, which exploits the selected SSD aligned to the built-in Cm-244 alpha source, is described in details

Solid state microdosimetry of a 148 MeV proton spread-out Bragg peak with a pixelated silicon telescope

A constant value of the Relative Biological Effectiveness (RBE), equal to 1.1, to weight the physical dose of proton therapy treatment planning collides with the experimental evidence of an increase of effectiveness along the depth dose profile, especially at the end of the particle range. In this context, it is desirable to develop new optimized treatment planning systems that account for a variable RBE when weighting the physical dose. In particular, due to the increasing interest on microdosimetry as a possible methodology for measuring physical quantities correlated with the biological effectiveness of the therapeutic beam, the development of new Tissue-Equivalent Proportional Counters (TEPCs) specifically designed for the clinical environment are in progress. In this framework, the silicon technology allows to produce solid state detectors of real micrometric dimensions. This is a valid alternative to the TEPC from a practical point of view, being simple, easy-of-use and more versatile. The feasibility of a solid state microdosimeter based on a monolithic double stage silicon telescope has been previously proposed and deeply investigated by comparing its response to the one obtained by reference TEPCs in various radiation fields. The device is constituted by a matrix of cylindrical elements, 2 μm in thickness and 9 μm in diameter, coupled to a single E stage, 500 μm in thickness. Each segmented ΔE stage acts as a solid state microdosimeter, while the E stage gives information on the energy of the impinging proton up to about 8 MeV. This work is dedicated to the description of the microdosimetric characterization of the 148 MeV energy-modulated proton beam at the radiobiological research line of the Trento Proton Therapy Centre by means of a pixelated silicon microdosimeter. All measurements were carried out at different positions across the spread-out Bragg peak (SOBP) and the corresponding microdosimetric distributions were derived by applying a novel extrapolation algorithm. Finally, microdosimetric assessment of Relative Biological Effectiveness was carried out by weighting the dose distribution of the lineal energy with the Loncol's biological weighting function. Benefits and possible limitations of this approach are discussed

Characterization of a Be(p,xn) neutron source for fission yields measurements

We report on measurements performed at The Svedberg Laboratory (TSL) to characterize a proton-neutron converter for independent fission yield studies at the IGISOL-JYFLTRAP facility (Jyv\"askyl\"a, Finland). A 30 MeV proton beam impinged on a 5 mm water-cooled Beryllium target. Two independent experimental techniques have been used to measure the neutron spectrum: a Time of Flight (TOF) system used to estimate the high-energy contribution, and a Bonner Sphere Spectrometer able to provide precise results from thermal energies up to 20 MeV. An overlap between the energy regions covered by the two systems will permit a cross-check of the results from the different techniques. In this paper, the measurement and analysis techniques will be presented together with some preliminary results.Comment: 3 pages, 3 figures, also submitted as proceedings of the International Conference on Nuclear Data for Science and Technology 201

Compact thermal neutron sensors for moderator-based neutron spectrometers

In the framework of the NESCOFI@BTF project of the Italian Institute of Nuclear Physics, different types of active thermal neutron sensors were studied by coupling semiconductor devices with a suitable radiator. The objective was to develop a detector of small dimensions with a proper sensitivity to use at different positions in a novel moderating assembly for neutron spectrometry. This work discusses the experimental activity carried out in the framework of the ERINDA program (PAC 3/9 2012) to characterise the performance of a thermal neutron pulse detector based on (6)Li

Microdosimetry on nanometric scale with a new low-pressure avalanche-confinement TEPC

The tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam, nevertheless no detailed information on the track structure of the impinging particles can be obtained, since the lower operation limit of common TEPCs is about 0.3 μm. On the other hand, the pattern of particle interactions is measured by track-nanodosimetry, which derives the single-event distribution of ionization cluster size at the nanometric scale. Anyway, only three nanodosimeters are available worldwide. A feasibility study for extending the performances of TEPC down to the nanometric region was performed and a novel avalanche-confinement TEPC was designed and constructed. This detector is constituted by a cylindrical chamber, based on a three-electrode structure, connected to a vacuum and gas flow system to ensure a continuous replacement of the tissue equivalent gas, thus allowing to simulate different biological site sizes in the range 300-25 nm. This TEPC can be calibrated by exploiting a built-in alpha source and a miniaturized solid-state detector as a trigger. Irradiations with photons, fast neutrons and two hadron beams demonstrated the good performances of the device. A satisfactory agreement with FLUKA simulations was obtained

Plasma-Based Longitudinal Evaluation of ESR1 Epigenetic Status in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer

Background: Endocrine therapy (ET) is the mainstay of treatment for hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer; however, adaptive mechanisms emerge in about 25\u201330% of cases through alterations in the estrogen receptor ligand-binding domain, with a consequent ligand-independent estrogen receptor activity. Epigenetic-mediated events are less known and potentially involved in alternative mechanisms of resistance. The aim of this study was to test the feasibility of estrogen receptor 1 (ESR1) epigenetic characterization through liquid biopsy and to show its potential longitudinal application for an early ET sensitivity assessment. Methods: A cohort of 49 women with hormone receptor-positive HER2-negative MBC was prospectively enrolled and characterized through circulating tumor DNA using methylation-specific droplet digital PCR (MS-ddPCR) before treatment start (BL) and after 3 months concomitantly with computed tomography (CT) scan restaging (EV1). ESR1 epigenetic status was defined by assessing the methylation of its main promoters (promA and promB). The most established cell-free tumor DNA (ctDNA) factors associated with ET resistance [ESR1 and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations] were assessed through next-generation sequencing. Associations were tested through Mann\u2013Whitney U test, matched pairs variations through Wilcoxon signed rank test, and survival was analyzed by log-rank test. Results: The ET backbone was mainly based on aromatase inhibitors (AIs) (70.83%) in association with CDK4/6 inhibitors (93.75%). Significantly lower promA levels at baseline were observed in patients with liver metastases (P = 0.0212) and in patients with ESR1 mutations (P = 0.0091). No significant impact on PFS was observed for promA (P = 0.3777) and promB (P = 0.7455) dichotomized at the median while a 652-fold increase in promB or in either promA or promB at EV1 resulted in a significantly worse prognosis (respectively P = 0.0189, P = 0.0294). A significant increase at EV1 was observed for promB among patients with PIK3CA mutation (P = 0.0173). A trend was observed for promB in ESR1 wild-type patients and for promA in the ESR1 mutant subgroup. Conclusion: The study proofed the concept of an epigenetic characterization strategy based on ctDNA and is capable of being integrated in the current clinical workflow to give useful insights on treatment sensitivity

Integrated quantitative PIXE analysis and EDX spectroscopy using a laser-driven particle source

Among the existing elemental characterization techniques, Particle Induced X-ray Emission (PIXE) and Energy Dispersive X-ray (EDX) spectroscopy are two of the most widely used in different scientific and technological fields. Here we present the first quantitative laser-driven PIXE and laser-driven EDX experimental investigation performed at the Centro de L\'aseres Pulsados in Salamanca. Thanks to their potential for compactness and portability, laser-driven particle sources are very appealing for materials science applications, especially for materials analysis techniques. We demonstrate the possibility to exploit the X-ray signal produced by the co-irradiation with both electrons and protons to identify the elements in the sample. We show that, using the proton beam only, we can successfully obtain quantitative information about the sample structure through laser-driven PIXE analysis. These results pave the way towards the development of a compact and multi-functional apparatus for the elemental analysis of materials based on a laser-driven particle source.Comment: This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ENSURE grant agreement No. 647554). Submitted to Science Advances on 20th May 2

Development of gamma insensitive silicon carbide diagnostics to qualify intense thermal and epithermal neutron fields

The e_LiBANS project aims at creating accelerator based compact neutron facilities for diverse interdisciplinary applications. After the successful setting up and characterization of a thermal neutron source based on a medical electron LINAC, a similar assembly for epithermal neutrons has been developed. The project is based on an Elekta 18 MV LINAC coupled with a photoconverter-moderator system which deploys the ({\gamma},n) photonuclear reaction to convert a bremsstrahlung photon beam into a neutron field. This communication describes the development of novel diagnostics to qualify the thermal and epithermal neutron fields that have been produced. In particular, a proof of concept for the use of silicon carbide photodiodes as a thermal neutron rate detector is presented.Comment: 10 pages, 10 figures, accepted for publication to JINST on the 17th April 202

INTENSE THERMAL NEUTRON FIELDS FROM A MEDICAL-TYPE LINAC: THE E_LIBANS PROJECT

The e_LiBANS project aims at producing intense thermal neutron fields for diverse interdisciplinary irradiation purposes. It makes use of a reconditioned medical electron LINAC, recently installed at the Physics Department and INFN in Torino, coupled to a dedicated photo-converter, developed within this collaboration, that uses (\u3b3,n) reaction within high Z targets. Produced neutrons are then moderated to thermal energies and concentrated in an irradiation volume. To measure and to characterize in real time the intense field inside the cavity new thermal neutron detectors were designed with high radiation resistance, low noise and very high neutron-to-photon discrimination capability. This article offers an overview of the e_LiBANS project and describes the results of the benchmark experiment