V. Monaco

Using a within-subject cross-over, vehicle-controlled design, we investigated the acute effects of benzodiazepine receptor ligands with different mechanisms of action on the displacement activities (scratching, self-grooming, and body shake) of seven male macaques living in social groups. Our aim was to test the discriminative validity of displacement activities as an ethopharmacological model of anxiety. Subjects were given i.m. lorazepam (0.10, 0.20, 0.25 mg/kg) and FG 7142 (0.1, 0.3, 1.0 mg/kg). The frequency of displacement activities was decreased by the anxiolytic lorazepam and increased by the anxiogenic FG 7142 in a dose-dependent manner. Displacement activities were apparently more sensitive to anxiolytic treatment than other behavior patterns indicative of an anxiety state (i.e., visual scanning of the social environment and fear responses directed to dominant males). These results suggest that primate displacement activities are a valid ethopharmacological model of anxiety. Anxiety 2:186–191 (1996). © 1996 Wiley-Liss, Inc.

In this paper we report on the timing resolution obtained in a beam test with pions of 180 GeV/c momentum at CERN for the first production of 45 µm thick Ultra-Fast Silicon Detectors (UFSD). UFSD are based on the Low-Gain Avalanche Detector (LGAD) design, employing n-on-p silicon sensors with internal charge multiplication due to the presence of a thin, low-resistivity diffusion layer below the junction. The UFSD used in this test had a pad area of 1.7 mm2. The gain was measured to vary between 5 and 70 depending on the sensor bias voltage. The experimental setup included three UFSD and a fast trigger consisting of a quartz bar readout by a SiPM. The timing resolution was determined by doing Gaussian fits to the time-of-flight of the particles between one or more UFSD and the trigger counter. For a single UFSD the resolution was measured to be 34 ps for a bias voltage of 200 V, and 27 ps for a bias voltage of 230 V. For the combination of 3 UFSD the timing resolution was 20 ps for a bias voltage of 200 V, and 16 ps for a bias voltage of 230 V.

Low-Gain Avalanche Diodes (LGAD) are silicon detectors with output signals that are about a factor of 10 larger than those of traditional sensors. In this paper we analyze how the design of LGAD can be optimized to exploit their increased output signal to reach optimum timing performances. Our simulations show that these sensors, the so-called Ultra-Fast Silicon Detectors (UFSD), will be able to reach a time resolution factor of 10 better than that of traditional silicon sensors.

This paper describes the system for the dose delivery currently used at the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated scanning radiotherapy.CNAO Foundation, Istituto Nazionale di Fisica Nucleare and University of Torino have designed, built, and commissioned a dose delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated synchrotron and to distribute the dose with a full 3D scanning technique. Protons and carbon ions are provided for a wide range of energies in order to cover a sizable span of treatment depths. The target volume, segmented in several layers orthogonally to the beam direction, is irradiated by thousands of pencil beams which must be steered and held to the prescribed positions until the prescribed number of particles has been delivered. For the CNAO beam lines, these operations are performed by the DDS. The main components of this system are two independent beam monitoring detectors, called BOX1 and BOX2, interfaced with two control systems performing the tasks of real-time fast and slow control, and connected to the scanning magnets and the beam chopper. As a reaction to any condition leading to a potential hazard, a DDS interlock signal is sent to the patient interlock system which immediately stops the irradiation. The essential tasks and operations performed by the DDS are described following the data flow from the treatment planning system through the end of the treatment delivery.The ability of the DDS to guarantee a safe and accurate treatment was validated during the commissioning phase by means of checks of the charge collection efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity and stability. A high level of reliability and robustness has been proven by three years of system activity needing rarely more than regular maintenance and working with 100% uptime. Four identical and independent DDS devices have been tested showing comparable performances and are presently in use on the CNAO beam lines for clinical activity.The dose delivery system described in this paper is one among the few worldwide existing systems to operate ion beam for modulated scanning radiotherapy. At the time of writing, it has been used to treat more than 350 patients and it has proven to guide and control the therapeutic pencil beams reaching performances well above clinical requirements. In particular, in terms of dose accuracy and stability, daily quality assurance measurements have shown dose deviations always lower than the acceptance threshold of 5% and 2.5%, respectively.

In this contribution we will review the progresses toward the construction of a tracking system able to measure the passage of charged particles with a combined precision of ∼10 ps and ∼10 μm, either using a single type of sensor, able to concurrently measure position and time, or a combination of position and time sensors.

Objective. In this study we introduce spatiotemporal emission reconstruction prompt gamma timing (SER-PGT), a new method to directly reconstruct the prompt photon emission in the space and time domains inside the patient in proton therapy.Approach. SER-PGT is based on the numerical optimisation of a multidimensional likelihood function, followed by a post-processing of the results. The current approach relies on a specific implementation of the maximum-likelihood expectation maximisation algorithm. The robustness of the method is guaranteed by the complete absence of any information about the target composition in the algorithm.Main results. Accurate Monte Carlo simulations indicate a range resolution of about 0.5 cm (standard deviation) when considering 107primary protons impinging on an homogeneous phantom. Preliminary results on an anthropomorphic phantom are also reported.Significance. By showing the feasibility for the reconstruction of the primary particle range using PET detectors, this study provides significant basis for the development of an hybrid in-beam PET and prompt photon device.

The DC-coupled Resistive Silicon Detectors (DC-RSD) are the evolution of the AC-coupled RSD (RSD) design, both based on the Low-Gain Avalanche Diode (LGAD) technology. The DC-RSD design concept intends to address a few known issues present in RSDs (e.g., baseline fluctuation, long tail-bipolar signals) while maintaining their advantages (e.g., signal spreading, 100% fill factor). The simulation of DC-RSD presents several unique challenges linked to the complex nature of its design and the large pixel size. The defining feature of DC-RSD, charge sharing over distances that can be as large as a millimetre, represents a formidable challenge for Technology-CAD (TCAD), the standard simulation tool. To circumvent this problem, we have developed a mixed-mode approach to the DC-RSD simulation, which exploits a combination of two simulation tools: TCAD and Spice. Thanks to this hybrid approach, it has been possible to demonstrate that, according to the simulation, the key features of the RSD, excellent timing and spatial resolutions (few tens of picoseconds and few microns), are maintained in the DC-RSD design. In this work, we present the developed models and methodology, mainly showing the results of device-level numerical simulation, which have been obtained with the state-of-the-art Synopsys Sentaurus TCAD suite of tools. Such results will provide all the necessary information for the first batch of DC-RSD produced by Fondazione Bruno Kessler (FBK) foundry in Trento, Italy.

Lorazepam (0.2 mg/kg IM) was given to group-living female macaques to assess the effect of anxiolytic treatment on scratching, a behavior pattern referred to as a displacement activity in the primate literature. Lorazepam selectively diminished scratching behavior. The drug effect was status-dependent: especially low-ranking animals showed a marked reduction in scratching. Lorazepam exerted a direct effect on scratching, that is the effect was not due to sedation or mediated by the influence of the drug on other behaviors. These results provide pharmacological validation to the ethological finding that scratching may be a manifestation of anxiety in monkeys. In addition, they suggest to use scratching as a behavioral measure in studies investigating nonhuman primate models of anxiety.

Is it possible to design a detector able to concurrently measure time and position with high precision? This question is at the root of the research and development of silicon sensors presented in this contribution. Silicon sensors are the most common type of particle detectors used for charged particle tracking, however their rather poor time resolution limits their use as precise timing detectors. A few years ago we have picked up the gantlet of enhancing the remarkable position resolution of silicon sensors with precise timing capability. I will be presenting our results in the following pages.

A fast 144-channel proton counter prototype, designed for monitoring the fluence rate of clinical proton beams, is based on a thin Low Gain Avalanche Detector (LGAD), segmented into 146 strips (114 μm width, 26214 μm length, 180 μm pitch). The layout of the sensor was designed in the framework of the Modeling and Verification for Ion beam Treatment planning (MoVe-IT) project in collaboration with Fondazione Bruno Kessler (FBK, Trento, Italy) and fourteen wafers were produced and delivered by FBK in 2020. In this paper, we present the laboratory characterization of the sensors performed on the entire wafer at FBK, right after production, and at the University of Turin after cutting the sensors using a probe station connected with a power device analyzer for static electrical tests and an infrared picosecond laser to study the dynamic properties. In addition, one sensor was tested with the clinical proton beam at National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy). The results obtained from the test at FBK and UNITO facilities demonstrated that the cut did not affect the yield production. The static electrical tests proved that the MoVe-IT-2020 sensors production was of very high quality. The width of the inter-strip dead region measured was 80.8 μm. 22% larger than the distance of the gain layers, and has a small dependence on laser intensities. A preliminary beam test at CNAO showed good separation between signal and noise in the LGAD strip, which allows counting properly the protons by selecting the optimal signal threshold.

The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at the SIS accelerator of GSI laboratory in Darmstadt has been designed for the measurement of ion fragmentation cross-sections at different angles and energies between 100 and 1000 MeV/nucleon. Nuclear fragmentation processes are relevant in several fields of basic research and applied physics and are of particular interest for tumor therapy and for space radiation protection applications. The start of the scientific program of the FIRST experiment was on summer 2011 and was focused on the measurement of 400 MeV/nucleon 12C beam fragmentation on thin (8 mm) graphite target. The detector is partly based on an already existing setup made of a dipole magnet (ALADiN), a time projection chamber (TP-MUSIC IV), a neutron detector (LAND) and a time of flight scintillator system (TOFWALL). This pre-existing setup has been integrated with newly designed detectors in the Interaction Region, around the carbon target placed in a sample changer. The new detectors are a scintillator Start Counter, a Beam Monitor drift chamber, a silicon Vertex Detector and a Proton Tagger scintillator system optimized for the detection of light fragments emitted at large angles. In this paper we review the experimental setup, then we present the simulation software, the data acquisition system and finally the trigger strategy of the experiment.

A new hadron-therapy facility implementing an active beam scanning technique has been developed at the Italian National Center of Oncological Hadron-therapy (CNAO). This paper presents the design and the characterization of the beam monitor detectors developed for the on-line monitoring and control of the dose delivered during a treatment at CNAO. The detectors are based on five parallel-plate transmission ionization chambers with either a single large electrode or electrodes segmented in 128 strips (strip chambers) and 32×32 pixels (pixel chamber). The detectors are arranged in two independent boxes with an active area larger than 200×200 mm2 and a total water equivalent thickness along the beam path of about 0.9 mm. A custom front-end chip with 64 channels converts the integrated ionization channels without dead-time. The detectors were tested at the clinical proton beam facility of the Paul Scherrer Institut (PSI) which implements a spot scanning technique, each spot being characterized by a predefined number of protons delivered with a pencil beam in a specified point of the irradiation field. The short-term instability was measured by delivering several identical spots in a time interval of few tenths of seconds and is found to be lower than 0.3%. The non-uniformity, measured by delivering sequences of spots in different points of the detector surface, results to be lower than 1% in the single electrode chambers and lower than 1.5% in the strip and pixel chambers, reducing to less than 0.5% and 1% in the restricted 100×100 mm2 central area of the detector.

Advanced ion beam therapeutic techniques, such as hypofractionation, respiratory gating, or laser-based pulsed beams, have dose rate time structures which are substantially different from those found in conventional approaches. The biological impact of the time structure is mediated through the β parameter in the linear quadratic (LQ) model. The aim of this study was to assess the impact of changes in the value of the β parameter on the treatment outcomes, also accounting for noninstantaneous intrafraction dose delivery or fractionation and comparing the effects of using different primary ions.An original formulation of the microdosimetric kinetic model (MKM) is used (named MCt-MKM), in which a Monte Carlo (MC) approach was introduced to account for the stochastic spatio-temporal correlations characteristic of the irradiations and the cellular repair kinetics. A modified version of the kinetic equations, validated on experimental cell survival in vitro data, was also introduced. The model, trained on the HSG cells, was used to evaluate the relative biological effectiveness (RBE) for treatments with acute and protracted fractions. Exemplary cases of prostate cancer irradiated with different ion beams were evaluated to assess the impact of the temporal effects.The LQ parameters for a range of cell lines (V79, HSG, and T1) and ion species (H, He, C, and Ne) were evaluated and compared with the experimental data available in the literature, with good results. Notably, in contrast to the original MKM formulation, the MCt-MKM explicitly predicts an ion and LET-dependent β compatible with observations. The data from a split-dose experiment were used to experimentally determine the value of the parameter related to the cellular repair kinetics. Concerning the clinical case considered, an RBE decrease was observed, depending on the dose, ion, and LET, exceeding up to 3% of the acute value in the case of a protraction in the delivery of 10 min. The intercomparison between different ions shows that the clinical optimality is strongly dependent on a complex interplay between the different physical and biological quantities considered.The present study provides a framework for exploiting the temporal effects of dose delivery. The results show the possibility of optimizing the treatment outcomes accounting for the correlation between the specific dose rate time structure and the spatial characteristic of the LET distribution, depending on the ion type used.

Robotics and related technologies are realizing their promise to improve the delivery of rehabilitation therapy but the mechanism by which they enhance recovery is still unknown. The electromechanical-driven gait orthosis Lokomat has demonstrated its utility for gait rehabilitation after stroke.To test the efficacy of Lokomat in gait retraining and to investigate the neurophysiological mechanisms underlying the recovery process.Case series study.Unit of Neurorehabilitation of a University Hospital.Fifteen patients with post-stroke hemiparesis.Patients underwent a six weeks rehabilitative treatment provided by Lokomat. The outcome measures were: Fugl-Meyer Motor Scale (FMMS), Berg Balance Scale (BBS), 10 metres Walking Test (10mWT), Timed Up and Go test (TUG), 6 Minute Walking Test (6MWT). Strength and Motor Unit firing rate of vastus medialis (VM) were analyzed during isometric knee extension through an isokinetic dynamometer and surface EMG recording.An increase of duration and covered distance, a decrease of body weight support and guidance force on the paretic side along the sessions were observed. The FMMS, the BBS, the TUG and the 6MWT demonstrated a significant improvement after the training. No increase of force was observed whereas a significant increase of firing rate of VM was recorded.The evidence that the improvement of walking ability observed in our study determines a significant increase of firing rate of VM not accompanied by an increase of force could suggest an effect of training on motorneuronal firing rate that thus contributes to improve motor control.Given the current wide use of robotics in gait retraining after stroke, our approach can contribute to clarify the mechanisms underlying its rehabilitative impact so as to incorporate the findings of evidence-based practice into appropriate treatment plans for persons poststroke.

A detailed knowledge of the light ions interaction processes with matter is of great interest in basic and applied physics. As an example, particle therapy and space radioprotection require highly accurate fragmentation cross-section measurements to develop shielding materials and estimate acute and late health risks for manned missions in space and for treatment planning in particle therapy. The Fragmentation of Ions Relevant for Space and Therapy experiment at the Helmholtz Center for Heavy Ion research (GSI) was designed and built by an international collaboration from France, Germany, Italy, and Spain for studying the collisions of a $^{12}\mathrm{C}$ ion beam with thin targets. The collaboration's main purpose is to provide the double-differential cross-section measurement of carbon-ion fragmentation at energies that are relevant for both tumor therapy and space radiation protection applications. Fragmentation cross sections of light ions impinging on a wide range of thin targets are also essential to validate the nuclear models implemented in MC simulations that, in such an energy range, fail to reproduce the data with the required accuracy. This paper presents the single differential carbon-ion fragmentation cross sections on a thin gold target, measured as a function of the fragment angle and kinetic energy in the forward angular region ($\ensuremath{\theta}\ensuremath{\lesssim}{6}^{\ensuremath{\circ}}$), aiming to provide useful data for the benchmarking of the simulation softwares used in light ions fragmentation applications. The $^{12}\mathrm{C}$ ions used in the measurement were accelerated at the energy of 400 MeV/nucleon by the SIS (heavy ion synchrotron) GSI facility.

The quality assurance (QA) procedures in particle therapy centers with active beam scanning make extensive use of films, which do not provide immediate results. The purpose of this work is to verify whether the 2D MatriXX detector by IBA Dosimetry has enough sensitivity to replace films in some of the measurements.MatriXX is a commercial detector composed of 32×32 parallel plate ionization chambers designed for pre-treatment dose verification in conventional radiation therapy. The detector and GAFCHROMIC® films were exposed simultaneously to a 131.44MeV proton and a 221.45MeV/u carbon-ion therapeutic beam at the CNAO therapy center of Pavia - Italy, and the results were analyzed and compared.The sensitivity MatriXX on the beam position, beam width and field flatness was investigated. For the first two quantities, a method for correcting systematic uncertainties, dependent on the beam size, was developed allowing to achieve a position resolution equal to 230μm for carbon ions and less than 100μm for protons. The beam size and the field flatness measured using MatriXX were compared with the same quantities measured with the irradiated film, showing a good agreement.The results indicate that a 2D detector such as MatriXX can be used to measure several parameters of a scanned ion beam quickly and precisely and suggest that the QA would benefit from a new protocol where the MatriXX detector is added to the existing systems.

The emergent FLASH RadioTherapy (RT) uses ultrahigh dose-rate irradiation (up to 107 Gy/s instantaneous dose-rate in each μs pulse) to deliver a single high dose of irradiation in a very short time (less than 200 milliseconds). Pre-clinical studies at ultrahigh dose-rates recently showed an increased ratio between tumoricidal effect and normal tissue toxicity (therapeutic index), compared to conventional RT at standard Gy/min dose-rates. If confirmed by biological in vivo validations, this could represent a breakthrough in cancer treatment. However, the reliability and the accuracy of experimental studies are nowadays limited by the lack of detectors able to measure online the beam fluence at FLASH dose-rates. The behaviour of standard beam monitors (gas-filled ionization chambers) is compromised by the volume recombination caused by the amount of charges created per unit volume and unit time, due to the large dose-rate. Moreover, due to the lack of proper monitoring devices and to the uncertainties of its future applications, very few facilities are able to deliver at present FLASH irradiations. In this contribution, we report about the physical and technological challenges of monitoring high and ultra-high dose-rates with electrons and photon beams, starting from the pre-clinical and clinical constraints for new devices. Based on the extensive experience in silicon detectors for monitoring applications in RT with external beams, the work then investigates silicon sensors as a possible option to tackle such extreme requirements and a rugged thin and large (e.g. 10×10 cm2) flat detector (silicon-based sensor + readout electronics) is therefore outlined. This study aims at presenting the FLASH-RT dosimetry problem and analysing the possibilities for a silicon sensor to be employed as sensing device for several FLASH scenarios, including some ideas on the readout part. However, more detailed simulations and studies are demanded to delineate more precisely the technical choices to be undertaken in order to tackle the clinical accuracy required on the beam fluence, typically a few %, during photon and electron high and ultra-high irradiations, the required minimal perturbation of the beam and the high level of radiation resistance.

We review the progress toward the development of a novel type of silicon detectors suited for tracking with a picosecond timing resolution, the so called Ultra-Fast Silicon Detectors. The goal is to create a new family of particle detectors merging excellent position and timing resolution with GHz counting capabilities, very low material budget, radiation resistance, fine granularity, low power, insensitivity to magnetic field, and affordability. We aim to achieve concurrent precisions of ∼ 10 ps and ∼ 10 μm with a 50 μm thick sensor. Ultra-Fast Silicon Detectors are based on the concept of Low-Gain Avalanche Detectors, which are silicon detectors with an internal multiplication mechanism so that they generate a signal which is factor ∼ 10 larger than standard silicon detectors.

To fully exploit the physics potentials of particle therapy in delivering dose with high accuracy and selectivity, charged particle therapy needs further improvement. To this scope, a multidisciplinary project (MoVeIT) of the Italian National Institute for Nuclear Physics (INFN) aims at translating research in charged particle therapy into clinical outcome. New models in the treatment planning system are being developed and validated, using dedicated devices for beam characterization and monitoring in radiobiological and clinical irradiations. Innovative silicon detectors with internal gain layer (LGAD) represent a promising option, overcoming the limits of currently used ionization chambers. Two devices are being developed: one to directly count individual protons at high rates, exploiting the large signal-to-noise ratio and fast collection time in small thicknesses (1 ns in 50 μm) of LGADs, the second to measure the beam energy with time-of-flight techniques, using LGADs optimized for excellent time resolutions (Ultra Fast Silicon Detectors, UFSDs). The preliminary results of first beam tests with therapeutic beam will be presented and discussed.

In microdosimetry, lineal energies y are calculated from energy depositions ϵ inside the microdosimeter divided by the mean chord length , whose value is based on geometrical assumptions on both the detector and the radiation field. This work presents an innovative two-stages hybrid detector (HDM: hybrid detector for microdosimetry) composed by a tissue equivalent proportional counter and a silicon tracker made of 4 low gain avalanche diode. This design provides a direct measurement of energy deposition in tissue as well as particles tracking with a submillimeter lateral spatial resolution. The data collected by the detector allow to obtain the real track length traversed by each particle in the tissue equivalent proportional counter and thus estimates microdosimetry spectra without the mean chord length approximation. Using Geant4 toolkit, we investigated HDM performances in terms of detection and tracking efficiencies when placed in water and exposed to protons and carbon ions in the therapeutic energy range. The results indicate that the mean chord length approximation underestimate particles with short track, which often are characterized by a high energy deposition and thus can be biologically relevant. Tracking efficiency depends on the low gain avalanche diode configurations: 34 strips sensors have a higher detection efficiency but lower spatial resolution than 71 strips sensors. Further studies will be performed both with Geant4 and experimentally to optimize the detector design on the bases of the radiation field of interest.The main purpose of HDM is to improve the assessment of the radiation biological effectiveness via microdosimetric measurements, exploiting a new definition of the lineal energy ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>y</mml:mi><mml:mi>T</mml:mi></mml:msub></mml:mrow></mml:math> ), defined as the energy deposition ϵ inside the microdosimeter divided by the real track length of the particle.

Abstract EXFLU1 is a new batch of radiation-resistant silicon sensors manufactured at Fondazione Bruno Kessler (FBK, Italy). The EXFLU1 sensors utilize thin substrates that remain operable even after extensive irradiation. They incorporate Low-Gain Avalanche Diode (LGAD) technology, enabling internal multiplication of charge carriers to boost the small signal produced by a particle crossing their thin active thicknesses, ranging from 15 to 45 μ m. To address current challenges related to acceptor removal, the EXFLU1 production incorporates improved defect engineering techniques. This includes the so called carbonated LGADs, where carbon doping is implanted alongside boron in the gain layer. This contribution focuses on evaluating the performances of thin sensors with carbonated gain layer from the EXFLU1 production, before and after irradiation up to 2.5· 10 15 n 1 Mev eq. /cm 2 . The conducted tests involve static and transient characterizations, including I-V and C-V measurements, as well as laser and β -source tests. This work aims to present the state of the art in LGAD sensor technology with a carbonated gain layer and shows the characterization of the most radiation-resistant LGAD sensors produced to date.

This paper summarizes the beam test results obtained with a Resistive Silicon Detector (RSD) (also called AC-Low Gain Avalanche Diode, AC-LGAD) pixel array tested at the DESY beam test facility with a 5 GeV/c electron beam. Furthermore, it describes in detail the simulation results of DC-RSD, an evolution of the RSD design. The simulations campaign described in this paper has been instrumental in the definition of the structures implemented in the Fondazione Bruno Kessler FBK first DC-RSD production. The RSD matrix used in this study is part of the second FBK RSD production, RSD2. The best position resolution reached in this test is σx=15 μm, about 3.4% of the pitch. DC-RSD LGAD, are an evolution of the AC-coupled design, eliminating the dielectric and using a DC-coupling to the electronics. The concept of DC-RSD has been finalized using full 3D Technology-CAD simulations of the sensor behavior. TCAD simulations are an excellent tool for designing this innovative class of detectors, enabling the evaluation of different technology options (e.g., the resistivity of the n+ layer, contact materials) and geometrical layouts (shape and distance of the read-out pads).

The 40 MHz bunched muon beam set up at CERN was used in May 2003 to make a full test of the drift tubes local muon trigger. The main goal of the test was to prove that the integration of the various devices located on a muon chamber was adequately done both on the hardware and software side of the system. Furthermore the test provided complete information about the general performance of the trigger algorithms in terms of efficiency and noise. Data were collected with the default configuration of the trigger devices and with several alternative configurations at various angles of incidence of the beam. Tests on noise suppression and di-muon trigger capability were performed.

In hadron therapy one of the most advanced methods for beam delivery is the active scanning technique which uses fast scanning magnets to drive a narrow particle beam across the target. The Centro Nazionale di Adroterapia Oncologica (CNAO) will treat tumours with this technique. The CNAO scanning system includes two identical dipole magnets for horizontal and vertical beam deflection, each one connected to a fast power supply. The dose delivery system exploits a set of monitor chambers to measure the fluence and position of the beam and drives the beam during the treatment by controlling the sequence of currents set by the power supplies. A test of the dynamic performance of the scanning system has been performed using a Hall probe to measure the field inside the magnet and the results are presented in this paper.

The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at GSI has been designed to study carbon fragmentation, measuring 12C double differential cross sections (∂2σ/∂θ∂E) for different beam energies between 100 and 1000 MeV/u. The experimental setup integrates newly designed detectors in the, so called, Interaction Region around the graphite target. The Interaction Region upstream detectors are a 250 μm thick scintillator and a drift chamber optimized for a precise measurement of the ions interaction time and position on the target. In this article we review the design of the upstream detectors along with the preliminary results of the data taking performed on August 2011 with 400 MeV/u fully stripped carbon ion beam at GSI. Detectors performances will be reviewed and compared to those obtained during preliminary tests, performed with 500 MeV electrons (at the BTF facility in the INFN Frascati Laboratories) and 80 MeV/u protons and carbon ions (at the INFN LNS Laboratories in Catania).

Hadrontherapy treatments use charged particles (e.g.protons and carbon ions) to treat tumors.During a therapeutic treatment with carbon ions, the beam undergoes nuclear fragmentation processes giving rise to significant yields of secondary charged particles.An accurate prediction of these production rates is necessary to estimate precisely the dose deposited into the tumours and the surrounding healthy tissues.Nowadays, a limited set of double differential carbon fragmentation cross-section is available.

Fast procedures for the beam quality assessment and for the monitoring of beam energy modulations during the irradiation are among the most urgent improvements in particle therapy. Indeed, the online measurement of the particle beam energy could allow assessing the range of penetration during treatments, encouraging the development of new dose delivery techniques for moving targets. Towards this end, the proof of concept of a new device, able to measure in a few seconds the energy of clinical proton beams (from 60 to 230 MeV) from the Time of Flight (ToF) of protons, is presented. The prototype consists of two Ultra Fast Silicon Detector (UFSD) pads, featuring an active thickness of 80 um and a sensitive area of 3 x 3 mm2, aligned along the beam direction in a telescope configuration, connected to a broadband amplifier and readout by a digitizer. Measurements were performed at the Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy), at five different clinical beam energies and four distances between the sensors (from 7 to 97 cm) for each energy. In order to derive the beam energy from the measured average ToF, several systematic effects were considered, Monte Carlo simulations were developed to validate the method and a global fit approach was adopted to calibrate the system. The results were benchmarked against the energy values obtained from the water equivalent depths provided by CNAO. Deviations of few hundreds of keV have been achieved for all considered proton beam energies for both 67 and 97 cm distances between the sensors and few seconds of irradiation were necessary to collect the required statistics. These preliminary results indicate that a telescope of UFSDs could achieve in a few seconds the accuracy required for the clinical application and therefore encourage further investigations towards the improvement and the optimization of the present prototype.

A new wide-input range 64-channels current-to-frequency converter ASIC has been developed and characterized for applications in beam monitoring of therapeutic particle beams. This chip, named TERA09, has been designed to extend the input current range, compared to the previous versions of the chip, for dealing with high-flux pulsed beams. A particular care was devoted in achieving a good conversion linearity over a wide bipolar input current range. Using a charge quantum of 200 fC, a linearity within ±2% for an input current range between 3 nA and 12 μA is obtained for individual channels, with a gain spread among the channels of about 3%. By connecting all the 64 channels of the chip to a common input, the current range can be increased 64 times preserving a linearity within ±3% in the range between and 20 μA and 750 μA.

Introduction. The fractures that occurred around trochanteric nails (perinail fractures, PNFs) are becoming a huge challenge for the orthopaedic surgeon. Although presenting some specific critical issues (i.e., patients’ outcomes and treatment strategies), these fractures are commonly described within peri-implant ones and their treatment was based on periprosthetic fracture recommendations. The knowledge gap about PNFs leads us to convene a research group with the aim to propose a specific classification system to guide the orthopaedic surgeon in the management of these fractures. Materials and Methods. A steering committee, identified by two Italian associations of orthopaedic surgeons, conducted a comprehensive literature review on PNFs to identify the unmet needs about this topic. Subsequently, a panel of experts was involved in a consensus meeting proposing a specific classification system and formulated treatment statements for PNFs. Results and Discussion. The research group considered four PNF main characteristics for the classification proposal: (1) fracture localization, (2) fracture morphology, (3) fracture fragmentation, and (3) healing status of the previous fracture. An alphanumeric code was included to identify each characteristic, allowing to describe up to 54 categories of PNFs, using a 3- to 4-digit code. The proposal of the consensus-based classification reporting the most relevant aspects for PNF treatment might be a useful tool to guide the orthopaedic surgeon in the appropriate management of these fractures.

The effects of age, sex, pregnancy, were analyzed and data from fasted and fed animals were compared in a population of cynomolgus macaques. No significant sex effects were observed for biochemical values and no changes were found in male hematological parameters in relation to age. Most values of females during pregnancy were within normal ranges. Comparison between fed and fasted animals showed that several biochemical parameters (e.g., ALT, glucose, CPK, LDH) and several hematological parameters (e.g., monocytes, eosinophils, basophils, hemoglobin, MCV, MCHC, and MCH) were affected by food intake.

One major rationale for the application of heavy ion beams in tumour therapy is their increased relative biological effectiveness (RBE). The complex dependencies of the RBE on dose, biological endpoint, position in the field etc require the use of biophysical models in treatment planning and clinical analysis. This study aims to introduce a new software, named 'Survival', to facilitate the radiobiological computations needed in ion therapy. The simulation toolkit was written in C++ and it was developed with a modular architecture in order to easily incorporate different radiobiological models. The following models were successfully implemented: the local effect model (LEM, version I, II and III) and variants of the microdosimetric-kinetic model (MKM). Different numerical evaluation approaches were also implemented: Monte Carlo (MC) numerical methods and a set of faster analytical approximations. Among the possible applications, the toolkit was used to reproduce the RBE versus LET for different ions (proton, He, C, O, Ne) and different cell lines (CHO, HSG). Intercomparison between different models (LEM and MKM) and computational approaches (MC and fast approximations) were performed. The developed software could represent an important tool for the evaluation of the biological effectiveness of charged particles in ion beam therapy, in particular when coupled with treatment simulations. Its modular architecture facilitates benchmarking and inter-comparison between different models and evaluation approaches. The code is open source (GPL2 license) and available at https://github.com/batuff/Survival.

Pile-up effects due to the overlap of signals within the system dead-time (τ) influence the counting capability of radiation detection devices, necessitating the use of correction algorithms to compensate for the count-losses at high radiation rates. Count-rate linearity is especially critical for clinical applications like X-ray imaging or beam monitoring in particle therapy. In particular, in proton therapy the number of delivered particles must be measured online during the treatment session with a maximum error of 1 % up to an average input beam flux of about 1010cm−2s−1. For a segmented detector used to identify and count the single beam particles, assuming a channel area of 1 mm2 and a dead-time τ=2ns, a maximum counting inefficiency of 1 % is required up to τ.fin=0.2 for each detector channel, where fin represents the input rate. Moreover, the beam is often delivered in bunches with higher instantaneous particle rates, and the saturation model of the detector and electronic chain could not be easily determined. Similar considerations are applicable for pixelated detectors used for photon counting. Two methods are proposed to mitigate counting inefficiencies with radiation sources of variable time-structures. Both methods are based on the collection of logic signals provided by two independent detector channels exposed to the same radiation field after discriminating the detector analog outputs with a fixed threshold, assuming that the duration of the discriminator output signal corresponds to the system dead-time. The correction algorithms employ the measurements of the time durations, the number of signals from the two channels and of their AND/OR combinations. The methods provide count-loss corrections without the need to know the dead-time model. The performances of the proposed algorithms are evaluated by using simulations of ideal boxcar signals of fixed duration τ, distributed randomly in time to emulate the dead-time behavior of the system. Both methods provide an effective count-loss correction with a maximum deviation of 1% for different input rates up to τ.fin=1, assuming a uniform random time distribution of input events for both paralyzable and non-paralyzable systems. The simulations of pulsed radiation fluxes provide the same results as a function of the instantaneous input rates. These results are similar to those obtainable by the standard live-time correction algorithm. However, the latter algorithm can only be applied to continuous particle fluxes, while the proposed algorithms work also for pulsed beams, without any hypothesis on the bunch duration or frequency. The robustness of the algorithms with respect to the resolution of the time measurement is studied and the potential limitations in more realistic systems are discussed. The algorithms can be easily implemented in standard logical circuits with multiple input signals provided by segmented detectors. Even if the methods are intended for real-time correction in beam particle counting, they could be applied in a wider range of applications of radiation measurements.

This work presents the tests of a multi-gap detector (MGD), composed of three parallel-plate ionization chambers (ICs) with different gap widths, assembled to prove the capability of correcting for charge volume recombination which is expected to occur when high fluence rates are delivered. Such beam conditions occur with a compact accelerator for charged particle therapy developed to reduce the costs, to accomplish faster treatments and to exploit different beam delivery techniques and dose rates as needed, for example, for range modulation and FLASH irradiations, respectively. The MGD was tested with carbon ions at the Centro Nazionale di Adroterapia Oncologica (CNAO Pavia, Italy), and with protons in two different beam lines: at Bern University Hospital with continuous beams and at the Laboratori Nazionale del Sud (Catania, Italy) of the Italian National Center of Nuclear Physics (INFN) with pulsed beams. For each accelerator, we took measurements with different beam intensities (up to the maximum rate of ionization achievable) and changed the detector bias voltage (V) in order to study the charge collection efficiency. Charge recombination models were used to evaluate the expected collected charge and to measure the linearity of the rate of ionization with the beam fluence rate. A phenomenological approach was used to determine the collection efficiency (f1) of the chamber with thinnest gap from the relative efficiencies, f1/f2 and f1/f3, exploiting the condition that, for each measurement, the three chambers were exposed to the same rate of ionization. Results prove that two calibration curves can be determined and used to correct the online measurements for the charge losses in the ICs for recombination.

Abstract Background The beam energy is one of the most significant parameters in particle therapy since it is directly correlated to the particles’ penetration depth inside the patient. Nowadays, the range accuracy is guaranteed by offline routine quality control checks mainly performed with water phantoms, 2D detectors with PMMA wedges, or multi‐layer ionization chambers. The latter feature low sensitivity, slow collection time, and response dependent on external parameters, which represent limiting factors for the quality controls of beams delivered with fast energy switching modalities, as foreseen in future treatments. In this context, a device based on solid‐state detectors technology, able to perform a direct and absolute beam energy measurement, is proposed as a viable alternative for quality assurance measurements and beam commissioning, paving the way for online range monitoring and treatment verification. Purpose This work follows the proof of concept of an energy monitoring system for clinical proton beams, based on Ultra Fast Silicon Detectors (featuring tenths of ps time resolution in 50 μm active thickness, and single particle detection capability) and time‐of‐flight techniques. An upgrade of such a system is presented here, together with the description of a dedicated self‐calibration method, proving that this second prototype is able to assess the mean particles energy of a monoenergetic beam without any constraint on the beam temporal structure, neither any a priori knowledge of the beam energy for the calibration of the system. Methods A new detector geometry, consisting of sensors segmented in strips, has been designed and implemented in order to enhance the statistics of coincident protons, thus improving the accuracy of the measured time differences. The prototype was tested on the cyclotron proton beam of the Trento Protontherapy Center (TPC). In addition, a dedicated self‐calibration method, exploiting the measurement of monoenergetic beams crossing the two telescope sensors for different flight distances, was introduced to remove the systematic uncertainties independently from any external reference. Results The novel calibration strategy was applied to the experimental data collected at TPC (Trento) and CNAO (Pavia). Deviations between measured and reference beam energies in the order of a few hundreds of keV with a maximum uncertainty of 0.5 MeV were found, in compliance with the clinically required water range accuracy of 1 mm. Conclusions The presented version of the telescope system, minimally perturbative of the beam, relies on a few seconds of acquisition time to achieve the required clinical accuracy and therefore represents a feasible solution for beam commission, quality assurance checks, and online beam energy monitoring.

Objective. The performance of silicon detectors with moderate internal gain, named low-gain avalanche diodes (LGADs), was studied to investigate their capability to discriminate and count single beam particles at high fluxes, in view of future applications for beam characterization and on-line beam monitoring in proton therapy.Approach. Dedicated LGAD detectors with an active thickness of 55μm and segmented in 2 mm2strips were characterized at two Italian proton-therapy facilities, CNAO in Pavia and the Proton Therapy Center of Trento, with proton beams provided by a synchrotron and a cyclotron, respectively. Signals from single beam particles were discriminated against a threshold and counted. The number of proton pulses for fixed energies and different particle fluxes was compared with the charge collected by a compact ionization chamber, to infer the input particle rates.Main results. The counting inefficiency due to the overlap of nearby signals was less than 1% up to particle rates in one strip of 1 MHz, corresponding to a mean fluence rate on the strip of about 5 × 107p/(cm2·s). Count-loss correction algorithms based on the logic combination of signals from two neighboring strips allow to extend the maximum counting rate by one order of magnitude. The same algorithms give additional information on the fine time structure of the beam.Significance. The direct counting of the number of beam protons with segmented silicon detectors allows to overcome some limitations of gas detectors typically employed for beam characterization and beam monitoring in particle therapy, providing faster response times, higher sensitivity, and independence of the counts from the particle energy.

A prototype of the CMS Barrel Muon Detector incorporating all the features of the final chambers was built using the mass production assembly procedures and tools. The performance of this prototype was studied in a muon test beam at CERN and the results obtained are presented in this paper.

Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

Nuclear fragmentation processes are relevant in different fields of basic research and applied physics and are of particular interest for tumor therapy and for space radiation protection applications. The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at SIS accelerator of GSI laboratory in Darmstadt, has been designed for the measurement of different ions fragmentation cross sections at different energies between 100 and 1000 MeV/nucleon. The experiment is performed by an international collaboration made of institutions from Germany, France, Italy and Spain. The experimental apparatus is partly based on an already existing setup made of the ALADIN magnet, the MUSIC IV TPC, the LAND2 neutron detector and the TOFWALL scintillator TOF system, integrated with newly designed detectors in the interaction Region (IR) around the carbon removable target: a scintillator Start Counter, a Beam Monitor drift chamber, a silicon Vertex Detector and a Proton Tagger for detection of light fragments emitted at large angles (KENTROS). The scientific program of the FIRST experiment started on summer 2011 with the study of the 400 MeV/nucleon 12C beam fragmentation on thin (8mm) carbon target.

In October 2001 the first produced CMS Barrel Drift Tube (DT) Muon Chamber was tested at the CERN Gamma Irradiation Facility (GIF) using a muon beam. A Resistive Plate Chamber (RPC) was attached to the top of the DT chamber, and, for the first time, both detectors were operated coupled together. The performance of the DT chamber was studied for several operating conditions, and for gamma rates similar to the ones expected at LHC. In this paper we present the data analysis; the results are considered fully satisfactory.

Abstract Beam monitoring in particle therapy is a critical task that, because of the high flux and the time structure of the beam, can be challenging for the instrumentation. Recent developments in thin silicon detectors with moderate internal gain, optimized for timing applications (Ultra Fast Silicon Detectors, UFSD), offer a favourable technological option to conventional ionization chambers. Thanks to their fast collection time and good signal-to-noise ratio, properly segmented sensors allow discriminating and counting single protons up to the high fluxes of a therapeutic beam, while the excellent time resolution can be exploited for measuring the proton beam energy using time-of-flight techniques. We report here the results of the first tests performed with UFSD detector pads on a therapeutic beam. It is found that the signal of protons can be easily discriminated from the noise, and that the very good time resolution is confirmed. However, a careful design is necessary to limit large pile-up inefficiencies and early performance degradation due to radiation damage.

The Ultra Fast Silicon Detectors (UFSD) are a novel concept of silicon detectors based on the Low Gain Avalanche Diode (LGAD) technology, which are able to obtain time resolution of the order of few tens of picoseconds. First prototypes with different geometries (pads/pixels/strips), thickness (300 and 50 μm) and gain (between 5 and 20) have been recently designed and manufactured by CNM (Centro Nacional de Microelectrónica, Barcelona) and FBK (Fondazione Bruno Kessler, Trento). Several measurements on these devices have been performed in laboratory and in beam test and a dependence of the gain on the temperature has been observed. Some of the first measurements will be shown (leakage current, breakdown voltage, gain and time resolution on the 300 μm from FBK and gain on the 50 μm-thick sensor from CNM) and a comparison with the theoretically predicted trend will be discussed.

In the framework of the development of future advanced treatment modalities in charged particle therapy, the use of silicon sensors is an appealing alternative to gas ionization chambers commonly used for beam monitoring. A prototype of a device, based on Low-Gain Avalanche Diode (LGAD) sensors with 50μm thickness, is being developed to discriminate and count single beam particles. This paper describes the design and characterization of ABACUS, an innovative multi-channel ASIC prototype for LGAD readout, based on a fast amplifier with self-reset capabilities. The design goals aim at detecting charge pulses in a wide range, from 4 fC to 150 fC, up to 70 MHz instantaneous rates, with a dead time of about 10 ns or less and efficiency larger than 98%. The characterization results indicate that even at the lowest input charge the signal-to-noise ratio is 15, high enough to keep full efficiency and preventing fake counts from the electronics noise. The dead time was found to be in the range between 5 ns and 10 ns, allowing to reach a full counting efficiency up to instantaneous rates of 70 MHz or larger, depending on the input charge.

A family of Application Specific Integrated Circuits ( ASICs ) called TERA have been developed for the readout of pixel and strip gas detectors used in radiotherapy applications. The TERA ASICs are based on the charge balancing integration technique in order to obtain a good linearity over a dynamic range of five order of magnitude.

A detector (MOPI) has been developed for the online monitoring of the beam at the Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA), where shallow tumours of the ocular region are treated with 62 MeV protons. At CATANA the beam is passively spread to match the tumour shape. The uniformity of the delivered dose depends on beam geometrical quantities which are checked before each treatment. However, beam instabilities might develop during the irradiation affecting the dose distribution. This paper reports on the use of the MOPI detector to measure the stability of the beam profile during the irradiation in the clinical practice. The results obtained in the treatment of 54 patients are also presented.

In-beam positron emission tomography (PET) monitoring can provide early treatment assessment in proton therapy. However, open ring configurations and low positron emitter production yields degrade image quality, hampering the assessment accuracy. To achieve the highest precision for range monitoring, it is compulsory to mitigate image noise and compensate for data truncation. The goal of this article is to study the performance of state-of-the-art algorithms for in-beam PET image reconstruction, by evaluating the impact of the system response model and assessing the accuracy of range measurements. The approaches investigated here were maximum-a-posteriori algorithms combined with total-variation and median-root priors. Maximum-likelihood-expectation-maximization was used as reference. To compute the system matrix, different models were compared: a precise Monte Carlo model, and single-ray tracing with and without Gaussian blurring in image space. The proposed methods were tested on simulations of spread-out-bragg-peaks delivered on phantoms. The in-beam PET innovative imaging scanner geometry was used as a case study. After image post-processing, the explored methods delivered similar results. This article demonstrates the feasibility and reliability of using a simple and fast reconstruction method to perform range evaluations, given the correct image post-processing.

Two drift tubes (DTs) chambers of the CMS muon barrel system were exposed to a 40 MHz bunched muon beam at the CERN SPS, and for the first time the whole CMS Level-1 DTs-based trigger system chain was tested. Data at different energies and inclination angles of the incident muon beam were collected, as well as data with and without an iron absorber placed between the two chambers, to simulate the electromagnetic shower development in CMS. Special data-taking runs were dedicated to test for the first time the Track Finder system, which reconstructs track trigger candidates by performing a proper matching of the muon segments delivered by the two chambers. The present paper describes the results of these measurements.

The development of the next generation of accelerators for charged particle radiotherapy aims to reduce dimensions and operational complexity of the machines by engineering pulsed beams accelerators. The drawback is the increased difficulty to monitor the beam delivery. Within each pulse, instantaneous currents larger by two to three orders of magnitude than present applications are expected, which would saturate the readout of the monitor chambers. In this paper, we report of a simple method to increase by almost two orders of magnitude the current range of an Application Specific Integrated Circuit chip previously developed by our group to read out monitor ionization chambers.

Abstract Quality assurance in particle therapy is an open issue that can be addressed with reliable monitoring techniques, such as in-beam PET and prompt-gamma-timing (PGT). In-beam PET is able to provide online feedback on the particle range by detecting the radiation related to the β + activity, while PGT relies on the time-of-flight (TOF) of prompt photons . The I3PET (In-beam PET Innovative Imaging) project is developing a novel scanner demonstrator that combines in-beam PET and PGT within the same detector, exploiting the potential synergy of these two techniques.

Hadrotherapy might be the last chance option for patients with cancers growing deep in the body or surrounded by very sensitive organs. The Italian National Center of Oncological Hadrotherapy (CNAO) in Pavia is a synchrotron based center for the treatment of tumors with protons and carbon ion beams. The result of this sophisticated technique is strongly affected by the beam delivery performances. A powerful on-line system to monitor and deliver particles inside the target will be available at CNAO.

Purpose A retrospective analysis of the dose delivery system (DDS) performances of the initial clinical operation at CNAO (Centro Nazionale di Adroterapia Oncologica) is reported, and compared with the dose delivery accuracy following the implementation of a position feedback control. Methods Log files and raw data of the DDS were analyzed for every field of patients treated with protons and carbon ions between January 2012 and April 2013 (~3800 fields). To investigate the DDS accuracy, the spot positions and the number of particles per spot measured by the DDS and prescribed by the treatment planning system were compared for each field. The impact of deviations on dose distributions was studied by comparing, through the gamma‐index method, 2 three‐dimensional (3D) physical dose maps (one for prescribed, one for measured data), generated by a validated dose computation software. The maximum gamma and the percentage of points with gamma ≤ 1 (passing volume) were studied as a function of the treatment day, and correlated with the deviations from the prescription in the measured number of particles and spot positions. Finally, delivered dose distributions of same treatment plans were compared before and after the implementation of a feedback algorithm for the correction of small position deviations, to study the effect on the delivery quality. A double comparison of prescribed and measured 3D maps, before and after feedback implementation, is reported and studied for a representative treatment delivered in 2012, redelivered on a polymethyl methacrylate (PMMA) block in 2018. Results Systematic deviations of spot positions, mainly due to beam lateral offsets, were always found within 1.5 mm, with the exception of the initial clinical period . The number of particles was very stable, as possible deviations are exclusively related to the quantization error in the conversion from monitor counts to particles. For the chosen representative patient treatment, the gamma‐index evaluation of prescribed and measured dose maps, before and after feedback implementation, showed a higher variability of maximum gamma for the 2012 irradiation, with respect to the reirradiation of 2018. However, the 2012 passing volume is &gt;99.8% for the sum of all fields, which is comparable to the value of 2018, with the exception of one day with 98.2% passing volume, probably related to an instability of the accelerating system. Conclusions A detailed retrospective analysis of the DDS performances in the initial period of CNAO clinical activity is reported. The spot position deviations are referable to beam lateral offset fluctuations, while almost no deviation was found in the number of particles. The impact of deviations on dose distributions showed that the position feedback implementation and the increased beam control capability acquired after the first years of clinical experience led to an evident improvement in the DDS stability, evaluated in terms of gamma‐index as a measure of the impact on dose distributions. However, the clinical effect of the maximum gamma variability found in the 2012 representative irradiation is mitigated by averaging along the number of fractions, and the high percentage of passing volumes confirmed the accuracy of the delivery even before the feedback implementation.

The design of a particle therapy system that integrates an innovative beam delivery concept based on a static toroidal gantry and an imaging configuration suitable for beam and online range monitoring is proposed and discussed. Such approach would provide a compact and cost-effective layout, with a highly flexible and fast beam delivery, single particle counting capability for fast measurement of beam fluence and position and a precise real time verification of the compliance between the treatment delivery and its prescription. The gantry configuration is discussed, presenting an analysis of the residual magnetic field in the bore and of the feasibility of irradiating a realistic target volume. Moreover, the expected performance of the PET-based range monitor is assessed through Monte Carlo simulations, showing a precision in the reconstruction of the activity distribution from a clinical treatment plan better than the state-of-the-art devices. The feasibility of the proposed design is then discussed through an assessment of the technological improvements required to actually start the construction and commissioning of a system prototype.

In this contribution, we present an innovative design of the Low-Gain Avalanche Diode (LGAD) gain layer, the p+ implant responsible for the local and controlled signal multiplication. In the standard LGAD design, the gain layer is obtained by implanting ∼5E16/cm3 atoms of an acceptor material, typically Boron or Gallium, in the region below the n++ electrode. In our design, we aim at designing a gain layer resulting from the overlap of a p+ and an n+ implants: the difference between acceptor and donor doping will result in an effective concentration of about 5E16/cm3, similar to standard LGADs. At present, the gain mechanism of LGAD sensors under irradiation is maintained up to a fluence of ∼1–2E15/cm2, and then it is lost due to the acceptor removal mechanism. The new design will be more resilient to radiation, as both acceptor and donor atoms will undergo removal with irradiation, but their difference will maintain constant. The compensated design will empower the 4D tracking ability typical of the LGAD sensors well above 1E16/cm2.

Abstract The University and the National Institute for Nuclear Physics of Torino are developing LGAD-based prototypes for beam monitoring in proton therapy. The direct measurement of single beam particles could overcome some features of currently used ionization chambers, such as slow charge collection and reduced sensitivity, which limit the implementation of advanced delivery techniques (e.g. rescanning). LGAD strip sensors have been designed and produced by Bruno Kessler Foundation (FBK, Trento) specifically for this project. A counter prototype to directly count individual protons at clinical fluence rates (10 6 –10 10 protons/cm 2 ·s) and a telescope system to measure the beam energy with time-of-flight (TOF) techniques are described. Tests of LGAD silicon strip sensors performed on synchrotron and cyclotron beams of therapeutic centers, using a pin-hole ionization chamber for the independent measurement of the particle flux, already showed the possibility to keep the counting error &lt;1% up to a beam fluence rate of few 10 8 protons/cm 2 ·s. The ongoing tests of counting sensors readout by a dedicated fast charge sensitive amplifier chip are reported. The telescope system, made of two sensors at a distance up to 95 cm, allows measuring the beam energy in the clinical range (70–230 MeV) with a maximum deviation of 310 keV in respect to the nominal one, with an uncertainty of 500 keV, thus achieving the prescribed clinical accuracy of 1 mm in the range in water.

The drift tubes based CMS barrel muon trigger, which uses self-triggering arrays of drift tubes, is able to perform the identification of the muon parent bunch crossing using a rather sophisticated algorithm. The identification is unique only if the trigger chain is correctly synchronized. Some beam test time was devoted to take data useful to investigate the synchronization of the trigger electronics with the machine clock. Possible alternatives were verified and the dependence on muon track properties was studied.

The aim of the present pilot study is to investigate the hypothesis that fall detection systems based on sensors placed on the distal segments of the body are more effective than solution based on placing sensors on the trunk. To test this hypothesis, we observed the contribution of all body segments to the 3D angular momentum. Five healthy adults were enrolled for the experimental sessions. A set of 39 spherical markers was located on body landmarks and subjects underwent perturbed walking while a Motion Analysis System recorded 3D kinematics. From a biomechanical model, the angular momentum pattern related to each body segment was estimated. Data were post-processed with a threshold-based algorithm used to detect which among body segments allows detect as soon as possible and with limited false alarms the perturbation. Results showed that hands-forearms and chest-head are the most sensitive to external moments orientated along respectively the anterior-posterior and medio-lateral directions.

In this contribution we present new developments in the production of Ultra Fast Silicon Detectors (UFSD) at Fondazione Bruno Kessler (FBK) in Trento, Italy. FBK after having in 2016 a successfully first production of UFSD sensors 300-micrometer thick, has produced in 2017 its first 50-micrometer thick UFSD sensors. These sensors use high resistivity Silicon on Silicon substrate and have different doping profile configurations of the gain layer based on Boron, Gallium, Carbonated Boron and Carbonated Gallium to obtain a controlled multiplication mechanism. The motivation of variety of gain layers it is to identify the most radiation hard technology to be employed in the production of UFSD for applications in high-radiation environments.

Spinal circuits play an important role in the generation of rhythmic motor activity, intermediating between descending signals and peripheral sensory information. The study of these circuits can provide a better understanding of the control mechanisms during the execution of cyclic motor tasks in healthy subjects or in patients with motor deficits due to a neurological disease. This work shows preliminary results regarding the estimation of spinal cord activity of post-stroke subjects obtained from the EMG signals by improving the computational model. This new model allows a better quantitative evaluation of motor performance in clinical contexts.

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation G. A. P. Cirrone, G. Cuttone, G. Candiano, M. Carpinelli, E. Leonora, D. Lo Presti, A. Musumarra, P. Pisciotta, L. Raffaele, N. Randazzo, F. Romano, F. Schillaci, V. Scuderi, A. Tramontana, R. Cirio, F. Marchetto, R. Sacchi, S. Giordanengo, V. Monaco; Absolute and relative dosimetry for ELIMED. AIP Conf. Proc. 26 July 2013; 1546 (1): 70–80. https://doi.org/10.1063/1.4816609 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioAIP Conference Proceedings Search Advanced Search |Citation Search

The development of Low-Gain Avalanche Diodes (LGADs) has made possible to manufacture silicon detectors with output signals that are about a factor of 10 larger than those of traditional sensors.This increased output brings many benefits such as the possibility of developing thin detectors with large enough signals, a good immunity towards low charge collection efficiency and it is key for excellent timing capabilities.In this paper, we report on the development of silicon sensors based on the LGAD design optimized to achieve excellent timing performance, the so-called Ultra-Fast Silicon Detectors (UFSDs).In particular, we demonstrate the possibility of obtaining ultra-fast silicon detectors with time resolution of less than 30 picosecond.

Nuclear fragmentation processes are relevant in different fields of physics concerning both basic research and applications. FIRST (Fragmentation of Ions Relevant for Space and Therapy) is an experiment aimed at the measurement of double differential cross sections (DDCS), with respect to kinetic energy and scattering polar angle, of nuclear fragmentation processes relevant for hadron therapy and for space radiation protection applications, in the energy range between 100 and 1000 MeV/u. The experiment was mounted at the GSI laboratories of Darmstadt, in Germany. A first data taking was performed in August 2011, using 400 MeV/u 12C on carbon and gold targets. In this work we present a description of the experimental apparatus and some figures from the data acquisition and from the preliminary work on data analysis.

Internationale Revue der gesamten Hydrobiologie und HydrographieVolume 3, Issue S1 p. fmi-fmi MastheadFree Access Masthead First published: 1911 https://doi.org/10.1002/iroh.19100030701AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume3, IssueS1Supplement: Hydrographische Supplemente1911Pages fmi-fmi RelatedInformation

Internationale Revue der gesamten Hydrobiologie und HydrographieVolume 3, Issue 5-6 p. fmi-fmi MastheadFree Access Masthead First published: 1911 https://doi.org/10.1002/iroh.19110030501AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume3, Issue5-61911Pages fmi-fmi RelatedInformation

Internationale Revue der gesamten Hydrobiologie und HydrographieVolume 3, Issue S2 p. fmi-fmi MastheadFree Access Masthead First published: 1911 https://doi.org/10.1002/iroh.19120030801AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume3, IssueS2Supplement: Hydrographische Supplemente1911Pages fmi-fmi RelatedInformation

The MIUR PRIN 4DInSiDe collaboration aims at developing the next generation of 4D (i.e., position and time) silicon detectors based on Low-Gain Avalanche Diodes (LGAD) that guarantee to operate efficiently in the future high-energy physics experiments. To this purpose, different areas of research have been identified, involving the development, design, fabrication and test of radiation-hard devices. This research has been enabled thanks to ad-hoc advanced TCAD modelling of LGAD devices, accounting for both technological issues as well as physical aspects, e.g. different avalanche generation models and combined surface and bulk radiation damage effects modelling. In this contribution, it is reviewed the progress and the relevant detector developments obtained during the research activities in the framework of the 4DInSiDe project. • TCAD modelling for the design of radiation-hard LGAD sensors for 4D tracking. • Gain layer compensation, (p ＋ - and n ＋ -doping) to preserve the gain at high fluences. • New design approach to resistive read-out sensors: DC-coupled RSD. • DC-RSD employs a direct coupling of the resistive layer to the read-out pads. • DC-coupled low resistivity strips between read-out pads to improve the resolution.

Recent developments in sensor design are opening the way to high resolution 4D-tracking detectors, able to measure concurrently position and time of passage of charged particles using the same sensitive device. The ongoing R&D path, based on the Low Gain Avalanche Diode (LGAD) technology, brings a new paradigm by introducing controlled signal sharing in the principles of operation of silicon sensors with the internal gain. The device under development is a thin LGAD with a resistive DC-coupled read-out (DC-coupled Resistive Silicon Detector - DC-RSD). The goal is to achieve a spatial resolution of a few micrometres using large pixels (150-200 micrometres), providing an excellent time resolution (~20-30 ps).The concept of DC-RSD has been finalized using an innovative mixed-mode approach to simulation: SPICE-based fast modeling to derive the sensor design parameters, followed by full 3D TCAD simulations of the sensor behaviour.This contribution reports the latest outcome of the simulations, which have been instrumental for the definition of the design technical implementation. This contribution also describes the characteristics of the first DC-RSD production at FBK, to be submitted in early summer, aimed at exploring multiple technological options and electrode layouts.Interesting information on the expected DC-RSD performance, extracted from recent experimental results obtained on AC-coupled resistive read-out sensors and on DC-RSD test structures, will be presented.

To describe a new system for scanned ion beam therapy, named RIDOS (Real-time Ion DOse planning and delivery System), which performs real time delivered dose verification integrating the information from a clinical beam monitoring system with a Graphic Processing Unit (GPU) based dose calculation in patient Computed Tomography.A benchmarked dose computation algorithm for scanned ion beams has been parallelized and adapted to run on a GPU architecture. A workstation equipped with a NVIDIA GPU has been interfaced through a National Instruments PXI-crate with the dose delivery system of the Italian National Center of Oncological Hadrontherapy (CNAO) to receive in real-time the measured beam parameters. Data from a patient monitoring system are also collected to associate the respiratory phases with each spot during the delivery of the dose. Using both measured and planned spot properties, RIDOS evaluates during the few seconds of inter-spill time the cumulative delivered and prescribed dose distributions and compares them through a fast γ-index algorithm.The accuracy of the GPU-based algorithms was assessed against the CPU-based ones and the differences were found below 1‰. The cumulative planned and delivered doses are computed at the end of each spill in about 300 ms, while the dose comparison takes approximatively 400 ms. The whole operation provides the results before the next spill starts.RIDOS system is able to provide a fast computation of the delivered dose in the inter-spill time of the CNAO facility and allows to monitor online the dose deposition accuracy all along the treatment.

The design of a single particle counter for therapeutical proton beams based on Low Gain Avalanche Diodes and optimized for very fast signals is carried on in the framework of the INFN MoVe-IT research project.Fast signal shaping front-end electronics is mandatory in this application in order to deal with particle rates of the order of hundreds of MHz per channel.Two preamplifier architectures, one based on a fast Charge Sensitive Amplifier with self-reset capabilities and a second one based on a Trans-Impedance Amplifier have been developed in a commercial CMOS 0.11 µm technology and submitted to the foundry.

Abstract The University of Torino (UniTO) and the National Institute for Nuclear Physics (INFN-TO) are investigating the use of Ultra Fast Silicon Detectors (UFSD) for beam monitoring in radiobiological experiments with therapeutic proton beams. The single particle identification approach of solid state detectors aims at increasing the sensitivity and reducing the response time of the conventional monitoring devices, based on gas detectors. Two prototype systems are being developed to count the number of beam particles and to measure the beam energy with time-of-flight (ToF) techniques. The clinically driven precision (&lt; 1%) in the number of particles delivered and the uncertainty &lt; 1 mm in the depth of penetration (range) in radiobiological experiments (up to 10 8 protons/s fluxes) are the goals to be pursued. The future translation into clinics would allow the implementation of faster and more accurate treatment modalities, nowadays prevented by the limits of state-of-the-art beam monitors. The experimental results performed with clinical proton beams at CNAO (Centro Nazionale di Adroterapia Oncologica, Pavia) and CPT (Centro di Protonterapia, Trento) showed a counting inefficiency &lt;2% up to 100 MHz/cm 2 , and a deviation of few hundreds of keV of measured beam energies with respect to nominal ones. The progresses of the project are reported.

Abstract A proton counter prototype based on Low Gain Avalanche Detector (LGAD) technology is being developed for the online monitoring of the fluence rate of therapeutic proton beams. The laboratory characterization of thin (45 μm and 60 μm) LGAD sensors segmented in 146 strips with an unprecedented large area of 2.6 × 2.6 cm 2 , covering the entire beam cross-section, is presented and discussed. The production includes 14 wafers with different characteristics, designed and produced at Fondazione Bruno Kessler (FBK) of Trento in 2020. The laboratory characterization was carried out at FBK, right after production, and at the University of Torino, after cutting the sensors, using a probe station with a power analyzer for the static DC electrical tests. The tests proved that the production was of very high quality. From 16 sensors randomly selected from different wafers, we observed consistency between the measurements performed at FBK and at the University of Torino, indicating that the cut did not degrade the performance. The sensors were also exposed to the clinical proton beam of the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy). The results show that LGADs allow achieving, in a very thin active thickness, a good separation between the proton signal, a peak of a very short duration, and the noise. This, combined with the large active area, will allow counting protons delivered with high efficiency at the high rates of a clinical beam.

It has been suggested that an atypical course of primary infection by EBV and the reactivation of EBV infection in transplanted patients may induce hepatitis. We explored the possibility to dissect the infectious activity from the ability to promote B lymphocyte proliferation in vivo by injecting in nu/nu mice a low number (2 x 10(6)-0.05 x 10(6)) of cells from CE a normal human bone marrow-derived B cell line. This line carries an endogenous EBV in episomal and linear forms. Twenty nu/nu mice were inoculated subcutaneously with the B cell line CE and a matched group with the cell line RAG obtained by EBV in vitro infection of normal human peripheral blood. The mice injected with the CE line did not develop a lymphoproliferative disease, but 5 of them displayed typical histopathological lesions of chronic hepatitis without involvement of other organs. Similar results were obtained in 2 out of 20 animals in the RAG group. A close association between liver lesions and a previous EBV infection, by putative circulating B lymphoblastoid cells releasing their EBV, was established by PCR and by in situ hybridization with BamHI "W" DNA probe. This latter probe detected the presence of about 15% of positive cells only in affected livers. In addition, the rare detection in some hepatocytes of "A" type Cowdry bodies would suggest the occurrence of continuous EBV replication although at a very low level. These data show that we succeeded in dissecting the infectious from the proliferative activity of the endogenous EBV carrier CE cell line. This provides in addition a promising model for chronic EBV-associated hepatitis.

Purpose: Nowadays new compact accelerators for charged particles beam therapy have been proposed where high beam intensities occur in short pulses. An innovative multi-gap ionization chamber is proposed which will allow to measure on-line high flux charged particle beams. Methods: The device includes three parallel ionization chambers with independent anodes and cathodes separated by gaps of different thicknesses filled with air. The charge produced in the gas by an ionizing particle is proportional to the gap width. Deviations from proportionality are expected with high flux beams because of inefficiencies due to charge recombination. The deviation from proportionality can be used to determine the collection efficiency and correct for it.The electronics read-out of each chamber is based on the 64-channel ASIC chip, designed in CMOS 0.35µm technology which features for each channel an independent current-to-frequency converter followed by a synchronous counter. The data acquisition system is based on NI FlexRIO FPGA module and LabView software. The monitor was preliminarily characterized with pulsed beam of photons produced by a 6 MeV Linac and with continuous beam of carbon ions at fixed energy of 120 MeV/u provided by a synchrotron. Later, it was tested with beam at much higher intensity, up to 100 nA, provided by a 18 MeV cyclotron. Results: The results with photons, protons and carbon ions beam show that the efficiency of the chamber is well described by Boag's theory. As expected, the efficiency increases with the voltage between the electrodes. The ionization density is derived from the efficiency by applying the Boag's theory and, in the case of photons, it is found to increase as the chamber is moved closer to the gamma source. Conclusion: The Multi-Gap Ionization Chamber to measure high flux charged particle beams was built. The design and preliminary characterization will be presented.

The effects of single and repeated doses of trimethyltin (TMT) treatment on the central nervous system (CNS) of the marmoset were investigated. For the acute-dose experiment adult animals were administered 3 mg/kg of TMT chloride (ip) and were then observed for changes in behavior. Within 24 hr postinjection all animals developed tremors, ataxia, and unresponsiveness. Half of the animals had severe clinical deterioration and died at 2 to 3 days following treatment. Surviving marmosets were sacrificed and the brain was subsequently perfusion-fixed for light microscopic examination. Neuronal degeneration was observed in many cells of the Ammon′s horn and fascia dentata of the hippocampus. For the chronic-dose experiment, adult marmosets received (ip) weekly doses of 0.75 mg/kg of TMT chloride for 24 weeks. No evident clinical signs or behavioral changes were observed in any of the treated animals. Histological examination revealed neuropathological changes comparatively similar but less severe than those observed in the acute-treated animals. The differences in toxicity effects between acute and chronic TMT administration are compared and discussed.

The Single Event Upset rate of a 64 channels integrated circuit, designed in CMOS $0.35 μm technology, has been measured and analyzed at the SIRAD facility of the Italian National Institute for Nuclear Physics (INFN). The chip, named TERA09, is a current to frequency converter designed to readout monitor chambers in particle therapy. In this field, the accelerator development is moving toward compact solutions providing high-intensity pulsed-beams. The TERA09 chip is capable to operate in a wide input current range, from few nA to hundreds of μA, with linearity deviations in the order of few percent. The chip is designed to be located aside of the monitoring chambers, far from the therapeutic beam, and no protection from data corruption from single events was implemented in its design. However, considering the relatively large area of the chip covered by data registers and the secondary neutrons field produced during the irradiation, the potential exposure to data corruption by Single Event Effect phenomena need to be addressed. The aim of the tests at SIRAD is to study the upset rate as a function of the energy deposited by single events by irradiating the chip with ions of different LET. From the analysis of the data it is possible to predict the single event effect cross-section in a clinical environment and estimate the readout failure probability in a real application scenario.

The CMS muon barrel drift tubes system has been recently fully installed and commissioned in the experiment. The performance and the current status of the detector are briefly presented and discussed.

The DDU board (Detector Dependent Unit, also called DT FED) is part of the Read-Out system of the CMS Drift-Tube detector. It merges data coming from the front-end electronics, in order to build an event fragment and send it to the global CMS DAQ through a S-LINK64 output. The DDU board also receives synchronization commands from the TTC system (Timing, Trigger and Control system), performs error detection on data and sends a fast feedback to the trigger system through the TTS output (Trigger Throttling System). The complete functionality of the DDU has been validated in laboratory and in the Cosmic Challenge exercise performed during summer 2006.

A 64 channels Application Specific Integrated Circuit, named TERA09, designed in a 0.35 μm technology for particle therapy applications, has been characterized for Single Event Upset probability. TERA09 is a current-to-frequency converter that offers a wide input range, extending from few nA to hundreds of μA, with linearity deviations in the order of a few percent. This device operates as front-end readout electronics for parallel plate ionization chambers adopted in clinical applications. This chip is going to be located beside the monitor chamber, thus not directly exposed to the particle beam. For this reason, no radiation hardening techniques were adopted during the microelectronics design. The intent of the test reported in this paper is to predict the TERA09 upset rate probability in a real application scenario. Due to the fact that TERA09 has an extended digital area with registers and counters, it is interesting to estimate the effect of the secondary neutron field produced during the treatment. The radiation damage test took place at the SIRAD facility of the Italian National Institute for Nuclear Physics in Padova, Italy. The SIRAD facility allows to study the CMOS upset rate as a function of the energy deposited during irradiation. By irradiating the chip with ions of different Linear Energy Transfer, it is possible to calculate the single event effect cross-section as a function of the deposited energy. It resulted that the minimum deposited energy in a CMOS silicon sensitive volume of 1μm3, responsible for a Single Event Upset probability higher than zero, is 690 keV. In the last part of the paper, we calculated the expected upset probability in a typical clinical environment, knowing the fluence of secondary, backward-emitted neutrons. Considering as an example a treatment room located at the CNAO particle therapy center in Pavia, the expected upset rate for TERA09 is ∼102 events/year. Using a redundant and independent monitor chamber, the upset probability expected during one detector readout is lower than 10−24, as explained in the document.

Purpose: The quality assurance (QA) procedure has to check the most relevant beam parameters to ensure the delivery of the correct dose to patients. Film dosimetry, which is commonly used for scanned ion beam QA, does not provide immediate results. The purpose of this work is to answer whether, for scanned ion beam therapy, film dosimetry can be replaced with the 2D MatriXX detector as a real‐time tool. Methods: MatriXX, equipped with 32×32 parallel plate ion‐chambers, is a commercial device intended for pre‐treatment verification of conventional radiation therapy.The MatriXX, placed at the isocenter, and GAFCHROMIC films, positioned on the MatriXX entrance, were exposed to 131.44 MeV proton and 221.45 MeV/u Carbon‐ion beams.The OmniPro‐I'mRT software, applied for the data taking of MatriXX, gives the possibility of acquiring consecutive snapshots. Using the NI LabVIEW, the data from snapshots were logged as text files for further analysis. Radiochromic films were scanned with EPSON scanner and analyzed using software programs developed in‐house for comparative purposes. Results: The field dose uniformity, flatness, beam position and beam width were investigated. The field flatness for the region covering 6×6 cm 2 square field was found to be better than 2%. The relative standard deviations, expected to be constant over 2×2, 4×4 and 6×6 pixels from MatriXX measurement gives a uniformity of 1.5% in good agreement with the film results.The beam center position is determined with a resolution better than 200 µm for Carbon and less than 100 µm for proton beam.The FWHM determination for a beam wider than 10 mm is satisfactory, whilst for smaller beams the determination is uncertain. Conclusion: Precise beam position and fast 2D dose distribution can be determined in real‐time using MatriXX detector. The results show that MatriXX is quick and accurate enough to be used in charged‐particle therapy QA.

Purpose: A description of a GPU-based dose delivery system (G-DDS) to integrate a fast forward planning implementing in real-time the prescribed sequence of pencil beams. The system, which is under development, is designed to evaluate the dose distribution deviations due to range variations and interplay effects affecting mobile tumors treatments. Methods: The Dose Delivery System (DDS) in use at the Italian Centro Nazionale di Adroterapia Oncologica (CNAO), is the starting point for the presented system. A fast and partial forward planning (FP) tool has been developed to evaluate in few seconds the delivered dose distributions using the DDS data (on-line measurements of spot properties, i.e. number of particles and positions). The computation is performed during the intervals between synchrotron spills and, made available at the end of each spill. In the interval between two spills, the G-DDS will evaluate the delivered dose distributions taking into account the real-time target positions measured by a tracking system. The sequence of prescribed pencil beams for the following spill will be adapted taking into account the variations with respect to the original plan due to the target motion. In order to speed up the computation required to modify pencil beams distribution (up to 400 times has been reached), the Graphics Processing Units (GPUs) and advanced Field Programmable Gate Arrays (FPGAs) are used. Results: An existing offline forward planning is going to be optimized for the CUDA architecture: the gain in time will be presented. The preliminary performances of the developed GPU-based FP algorithms will be shown. Conclusion: A prototype of a GPU-based dose delivery system is under development and will be presented. The system workflow will be illustrated together with the approach adopted to integrate the three main systems, i.e. CNAO dose delivery system, fast forward planning, and tumor tracking system.

A multi-gap ionization monitor chamber has been developed by INFN and Torino University, for monitoring of high intensity pulsed charged particle beams. The read-out of the chamber is based on a 64-channel ASIC, designed in CMOS 0.35μm technology which features for each channel an independent current-to-frequency converter followed by a synchronous counter. The chip was designed for connecting each channel to a different detector element. However, high beam intensities may lead to an input current above the saturation level of a single channel. A novel readout has been tested where all the input channels of the chip have been connected in parallel to the same detector element allowing to reach 64-times higher input current with only a modest deterioration of the resolution. Results will be presented in terms of linearity and noise, and will be compared to a simulation where the chip is modeled as a set of independent and uncorrelated channels.

Introduction: The Italian hadrontherapy center (CNAO) uses actively scanned proton and carbon-ion beams to treat tumors and is equipped with a dose delivery system (DDS) to monitor and guide the beams to the patient. This work aims at evaluating the impact of the DDS inaccuracies on the dose distribution of patients treated at CNAO through a retrospective analysis of the data collected during the delivery (D) and their comparison with the planning (P).

In this paper we report on the timing resolution of the first production of 50 micro-meter thick Ultra-Fast Silicon Detectors (UFSD) as obtained in a beam test with pions of 180 GeV/c momentum. UFSD are based on the Low-Gain Avalanche Detectors (LGAD) design, employing n-on-p silicon sensors with internal charge multiplication due to the presence of a thin, low-resistivity diffusion layer below the junction. The UFSD used in this test belongs to the first production of thin (50 {\mu}m) sensors, with an pad area of 1.4 mm2. The gain was measured to vary between 5 and 70 depending on the bias voltage. The experimental setup included three UFSD and a fast trigger consisting of a quartz bar readout by a SiPM. The timing resolution, determined comparing the time of arrival of the particle in one or more UFSD and the trigger counter, for single UFSD was measured to be 35 ps for a bias voltage of 200 V, and 26 ps for a bias voltage of 240 V, and for the combination of 3 UFSD to be 20 ps for a bias voltage of 200 V, and 15 ps for a bias voltage of 240 V.

Purpose: Monitoring the prescribed dose in particle therapy is typically carried out by using parallel plate ionization chambers working in transmission mode. The use of gas detectors has several drawbacks: they need to be calibrated daily against standard dosimeters and their dependence on beam quality factors need to be fully characterized and controlled with high accuracy. A detector capable of single particle counting is proposed which would overcome all these limitations. Combined with a gas ionization chamber, it will allow determining the average particle stopping power, thus providing an effective method for the online verification of the selected particle energy and range. Methods: Low‐Gain Avalanche Detectors (LGADs) are innovative n‐in‐p silicon sensors with moderate internal charge multiplication occurring in the strong field generated by an additional p+ doping layer implanted at a depth of a few µm in the bulk of the sensor. The increased signal‐to‐noise ratio allows designing very thin, few tens of microns, segmented LGADs, called Ultra Fast Silicon Detectors (UFSD), optimized for very fast signal, which would be suitable for charged particle counting at high rates. A prototype UFSD is being designed for this purpose. Results: Different LGAD diodes have been characterized both in laboratory and beam tests, and the results compared both with those obtained with similar diodes without the gain layer and with a program simulating the signal in the sensors. The signal is found to be enhanced in LGADs, while the leakage current and the noise is not affected by the gain. Possible alternative designs and implementations are also presented and discussed. Conclusion: Thanks to their excellent counting capabilities, UFSD detectors are a promising technology for future beam monitor devices in hadron‐therapy applications. Studies are ongoing to better understand their properties and optimize the design in view of this application.

Abstract The size and the number of thyroid masses in medium larval, climax, and postmetamorphic developmental stages of Pleurodeles waltl were examined in histological sections. Morphological data were also obtained from postmetamorphic specimens, that had been treated for a year with thiourea. In addition to a pair of lateral thyroid glands that developed during larval stages, microscopic examination revealed the presence of two or three supernumerary thyroid glands that were very small in the climax stage, but increased appreciably in size and development in 1‐year‐old postmetamorphic animals. Structural modifications in the supernumerary thyroids similar to those observed in the lateral thyroid glands were observed in thiourea‐exposed, postmetamorphic animals. These super numerary thyroids can be classified as one or two thyroid glands located in the anterior medial sagittal region of the lower jaw, and one posterior thyroid gland located in a left parasagktal region near the pericardial sac. On the basis of the thyroid control on body development and growth in the postmetamorphic stage, reported in other studies, including our own, and of the postmetamorphic mor phology of the supernumerary thyroid glands in P. waltl, an evolutive adaptation of the thyroid system to the habitat of this species is hypothesized. Key words: Pleurodeles waltl Thyroid glandsThyroid folliclesMetamorphosisThiourea

Some developmental parameters in the larval, climax and postmetamorphic stages of Triturus vittatus ophryticus and Triturus carnifex were compared in order to identify interspecific differences within the genus Triturus . Seventy larvae from each investigated species were reared in the same experimental conditions from hatching to the postmetamorphic stage. Biometric (body weights, total body lengths, snout-vent lengths) and histological data (density of epidermic glands) were collected in ten specimens randomly chosen after hatching, from thirty days old larvae, at climax and at the first postmetamorphic stage. Dry-substrate migration trend in the first postmetamorphic life was also estimated. Higher developmental rates attained during metamorphosis, smaller body size in the climax and in the first postmetamorphic stages, higher dry-substrate migration pattern and lower glandular density in the skin were observed in Triturus vittatus ophryticus when compared to Triturus carnifex . Our data show remarkably differences of the developmental patterns in Triturus vittatus ophryticus and Triturus carnifex . The observed differences are correlated and discussed, taking into account some ethological peculiarities of the two species.

The knowledge about fragmentation processes in ion-ion interactions is fundamental in hadrontherapy and radiation protection in space missions. Hadrontherapy, based on <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">12</sup> C, features many advantages with respect to conventional radiation therapy with photons due to the possibility to shape the dose delivery region in tissues but side effects of the projectile fragmentation in healthy tissues are not negligible. NASA recently pointed out that measurements for some light ions and kinetic energies are missing in nuclear fragmentation databases. FIRST experiment aims to measure the fragmentation double differential cross section of <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">12</sup> C in the energy range 1001000 MeV/u on several elements, constituents of organic tissues and electronic devices, in order to fill some of the mentioned lack of information on light ions. A first set of data has been taken in 2011 at GSI (Darmstadt), using <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">12</sup> C beam at 400 MeV/u on C and Au targets. About 3·10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sup> events with C target and 5 · 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> with Au target were recorded. Together with these data other sets of runs have been collected to calibrate the forward part of the whole experimental setup, the ToF-Wall. The calibration procedure and the detector performances, which fit the experiment requirements for what concerns efficiency, resolution and stability, will be illustrated. Moreover, some preliminary results concerning the <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">12</sup> C- <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">12</sup> C elastic scattering, in agreement with the Rutherford model, will be presented.

KENTROS (Kinetic ENergy and Time Resolution Optimized on Scintillator) is a relatively compact detector has been projected and constructed in the framework of the INFN FRAG and TPS experiments. KENTROS has been designed for energy deposition and time of flight measurements of charged particles. The detector ensures an angular coverage from about 5 degrees up to about 90 degrees polar angle in the laboratory frame. Recently KENTROS has been used as part of the FIRST experiment, devoted to measure double differential fragmentation cross sections, with the aim to detect light fragments produced in the nuclear fragmentation process.

Introduction Hadron-therapy is an effective technique used to treat tumors that are located between or nearby vital organs. The Italian National Center of Oncological Hadron-therapy (CNAO) has been realized as the first facility in Italy to treat very difficult tumors with protons and Carbon ions. The on-line monitor system for CNAO has been developed by the Department of Physics of the University of Torino and Italian National Institute of Nuclear Physics (INFN). The monitoring system performs the on-line checking of the beam intensity, dimension, and beam position. Materials and Methods The monitor system is based on parallel plate ionization chambers and is composed of five ionization chambers with the anodes fully integrated or segmented in pixels or strips that are placed in two boxes. A series of measurements were performed that involve the background current and the detectors have been characterized by means of a series of preliminary testes in order to verify reproducibility and uniformity of the chambers using an X-ray source. Results The measured background currents for StripX, StripY and Pixel chambers are five orders of magnitude smaller than the nominal treatment current. The reproducibility error of chambers is less than 1%. The analysis of the uniformity showed that the monitor devices have a spread in gain that varies, but only about 2%. Conclusion The reproducibility and the uniformity values are considered as a good result, taking into account that the X-ray energy range is several orders of magnitude smaller than the particle energies used at CNAO.