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Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/mu m on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately following irradiation in a dose-dependent manner. The analysis of repair capability showed that the cells irradiated with 1 and 2 Gy almost completely recovered from the damage, but not, however, 3 Gy treated cells in which DNA damage was not recovered. In addition, the results indicate the importance of the use of an appropriate control in radiobiological in vitro analysis.

Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (~19 keV/μm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual γ-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ~1.48 in the SOBP and ~1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28–42 mm away from the primary beam suggesting minimal risk from long-range secondary particles.

Thomson Parabola (TP) spectrometers are widely used devices for laser-driven beam diagnostics as they provide a complete set of information on the accelerated particles. A novel TP has been developed at LNS with a design able to detect protons up to 20 MeV. The layout design and some results obtained during the experimental campaign at PALS laboratory will be reported in the following.

The definition of detectors, methods and procedures for the absolute and relative dosimetry of laser-driven proton beams is a crucial step toward the clinical use of this new kind of beams. Hence, one of the ELIMED task, will be the definition of procedures aiming to obtain an absolute dose measure at the end of the transport beamline with an accuracy as close as possible to the one required for clinical applications (i.e. of the order of 5% or less). Relative dosimetry procedures must be established, as well: they are necessary in order to determine and verify the beam dose distributions and to monitor the beam fluence and the energetic spectra during irradiations. Radiochromic films, CR39, Faraday Cup, Secondary Emission Monitor (SEM) and transmission ionization chamber will be considered, designed and studied in order to perform a fully dosimetric characterization of the ELIMED proton beam.

In the framework of the ELIMED project, Monte Carlo (MC) simulations are widely used to study the physical transport of charged particles generated by laser-target interactions and to preliminarily evaluate fluence and dose distributions. An energy selection system and the experimental setup for the TARANIS laser facility in Belfast (UK) have been already simulated with the GEANT4 (GEometry ANd Tracking) MC toolkit. Preliminary results are reported here. Future developments are planned to implement a MC based 3D treatment planning in order to optimize shots number and dose delivery.

Laser-ion acceleration has recently gained a great interest as an alternative to conventional and more expensive acceleration techniques. These ion beams have desirable qualities such as small source size, high luminosity and small emittance to be used in different fields as Nuclear Physics, Medical Physics, etc. This is very promising specially for the future perspective of a new concept of hadrontherapy based on laser-based devices could be developed, replacing traditional accelerating machines. Before delivering laser-driven beams for treatments they have to be handled, cleaned from unwanted particles and characterized in order to have the clinical requirements. In fact ion energy spectra have exponential trend, almost 100% energy spread and a wide angular divergence which is the biggest issue in the beam transport and, hence, in a wider use of this technology. In order to demonstrate the clinical applicability of laser-driven beams new collaboration between ELI-Beamlines project researchers from Prague (Cz) and a INFN-LNS group from Catania (I) has been already launched and scientists from different countries have already express their will in joining the project. This cooperation has been named ELIMED (MEDical application at ELIBeamlines) and will take place inside the ELI-Beamlines infrastructure located in Prague. This work describes the schedule of the ELIMED project and the design of the energy selector which will be realized at INFN-LNS. The device is an important part of the whole transport beam line which will be realised in order to make the ion beams suitable for medical applications.

Nuclear fragmentation measurements are necessary in hadrontherapy and space radiation protection, to predict the effects of the ion nuclear interactions within the human body. Nowadays, a very limited set of carbon fragmentation cross sections has been measured and in particular, to our knowledge, no double differential fragmentation cross sections at intermediate energies are available in literature. We have measured the double differential cross sections and the angular distributions of the secondary fragments produced in the 12C fragmentation at 62 AMeV on a thin carbon target. The experimental data have been also used to benchmark the prediction capability of the Geant4 Monte Carlo code at intermediate energies, where it was never tested before.

The PRIMA (Proton IMAging) experiment is aimed at developing a proton Computed Tomography (pCT) prototype based on tracking single protons. Approaches to the pCT consist in the use of silicon microstrip detectors to measure the position and direction of individual protons before and after they traverse the phantom, in view to reconstruct the trajectory of each proton, and a calorimeter for measuring particle residual energy. A small prototype was tested, under 62 MeV proton beam at Laboratory Nazionali del Sud, (Catania Italy) and under 180 MeV proton beam at Svedberg Laboratories, Uppsala Universitet, (Uppsala Sweden). Several experiments concerning proton imaging, tomography and radiography, were carried out during these beam tests. Radiographies have been reconstructed with different methods: results show the good performances of the device, with spatial resolution fulfilling the stringent requirements of a pCT device.

Proton Computed Tomography (pCT) is a medical imaging technique based on the use of proton beams with energies above 200 MeV to directly measure stopping power distributions inside the tissue volume. Prima (PRoton IMAging) is an Italian collaboration working on the development of a pCT scanner based on a tracker and a calorimeter to measure single protons trajectory and residual energy. The tracker is composed of four planes of silicon microstrip detectors to measure proton entry and exit positions and angles. Residual energy is measured by a calorimeter composed of YAG:Ce scintillating crystals. A first prototype of pCT scanner, with an active area of about 5×5 cm2, has been constructed and characterized with 60 MeV protons at the INFN Laboratori Nazionali del Sud, Catania (Italy) and with 180 MeV protons at Svedberg Laboratory, Uppsala (Sweden). A new pre-clinical prototype with an extended active area up to 20×5 cm2, real time data acquisition and a data rate up to 1 MHz is under development. A description of the two prototypes will be presented together with first results concerning tomographic image reconstruction.

The knowledge about fragmentation processes in ion-ion interactions is fundamental in hadrontherapy and radiation protection in space missions. Hadrontherapy, based on 12C, 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 doubledifferential cross section of 12C in the energy range 100-1000 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 12C beam at 400 MeV/u on C and Au targets. About 3·107 events with C target and 5 × 106 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 12C-12C elastic scattering, in agreement with the Rutherford model, will be presented.

This paper presents the design flow of a detector for tracking charged particles together with the characterization techniques developed to extract the main design specifications. The goals for the final detector are to achieve real-time imaging, a large detection area and a high spatial resolution particularly suitable for medical imaging applications. The main concepts have been patented by the INFN. This paper describes the prototype tracker, which has a 20x20 cm2 sensitive area consisting of two crossed ribbons of 500 µm square scintillating fibers. The track position information is real-time extracted in an innovative way, using a reduced number of read-out channels to obtain a very large detection area but with moderate costs and complexity. The performance of the tracker has been investigated using s sources, cosmic rays, and a 62 MeV proton beam.

The main purpose of the present study is to investigate the possibility to characterize the particle beams produced by the laser-target interaction in terms of collection, focusing and energy selection in order to evaluate the feasibility of a laser-driven facility in the field of medical application and, in particular, for hadrontherapy.

The prototype of the OFFSET (Optical Fiber Folded Scintillating Extended Tracker) tracker is presented. It exploits a novel system for particle tracking, designed to achieve real-time imaging, large detection areas, and a high spatial resolution especially suitable for use in medical diagnostics. The main results regarding the system architecture have been used as a demonstration of the technique which has been patented by the Istituto Nazionale di Fisica Nucleare (INFN). The prototype of this tracker, presented in this paper, has a 20 × 20 cm2 sensitive area, consisting of two crossed ribbons of 500 micron square scintillating fibers. The track position information is extracted in real time in an innovative way, using a reduced number of read-out channels to obtain very large detection area with moderate enough costs and complexity. The performance of the tracker was investigated using beta sources, cosmic rays, and a 62 MeV proton beam.

We propose a series of simulations about the potential use of Boron isotopes to trigger neutron-free (aneutronic) nuclear reactions in cancer cells through the interaction with an incoming energetic proton beam, thus resulting in the emission of characteristic prompt gamma radiation (429 keV, 718 keV and 1435 keV). Furthermore assuming that the Boron isotopes are absorbed in cancer cells, the three alpha-particles produced in each p-11B aneutronic nuclear fusion reactions can potentially result in the enhancement of the biological dose absorbed in the tumor region since these multi-MeV alpha-particles are stopped inside the single cancer cell, thus allowing to spare the surrounding tissues. Although a similar approach based on the use of 11B nuclei has been proposed in [Yoon et al. Applied Physics Letters 105, 223507 (2014)], our work demonstrate, using Monte Carlo simulations, the crucial importance of the use of 10B nuclei (in a solution containing also 11B) for the generation of prompt gamma-rays, which can be applied to medical imaging. In fact, we demonstrate that the use of 10B nuclei can enhance the intensity of the 718 keV gamma-ray peak more than 30 times compared to the solution containing only 11B nuclei. A detailed explanation of the origin of the different prompt gamma-rays, as well as of their application as real-time diagnostics during a potential cancer treatment, is here discussed.

A magnetic chicane based on four electromagnetic dipoles is going to be realized by INFN-LNS to be used as an Energy Selection System (ESS) for laser driven proton beams up to 300 MeV and C6+ up to 70 MeV/u. The system will provide, as output, ion beams with a contrallable energy spread varying from 5% up to 20% according to the aperture slit size. Moreover, it has a very wide acceptance in order to ensure a very high transmission efficiency and, in principle, it has been designed to be used also as an active energy modulator. This system is the core element of the ELIMED (ELI-Beamlines MEDical and Multidisciplinary applications) beam transport, dosimetry and irradiation line that will be developed by INFN-LNS (It) and installed at the ELI-Beamlines facility in Prague (Cz). ELIMED will be the first user's open transport beam-line where a controlled laser-driven ion beam will be used for multidisciplinary research. The definition of well specified characteristics, both in terms of performance and field quality, of the magnetic chicane is crucial for the system realization, for the accurate study of the beam dynamics and for the proper matching with the Permanent Magnet Quadrupoles (PMQs) used as a collection system already designed. Here, the design of the magnetic chicane is described in details together with the adopted solutions in order to realize a robust system form the magnetic point of view. Moreover, the first preliminary transport simulations are also described showing the good performance of the whole beam line (PMQs+ESS).

Laser-based accelerators are gaining interest in recent years as an alternative to conventional machines [1]. In the actual ion acceleration scheme, energy and angular spread of the laser-driven beams are the main limiting factors for beam applications and different solutions for dedicated beam-transport lines have been proposed [2,3]. In this context a system of Permanent Magnet Quadrupoles (PMQs) has been realized [2] by INFN-LNS (Laboratori Nazionali del Sud of the Instituto Nazionale di Fisica Nucleare) researchers, in collaboration with SIGMAPHI company in France, to be used as a collection and pre-selection system for laser driven proton beams. This system is meant to be a prototype to a more performing one [3] to be installed at ELI-Beamlines for the collection of ions. The final system is designed for protons and carbons up to 60 MeV/u. In order to validate the design and the performances of this large bore, compact, high gradient magnetic system prototype an experimental campaign have been carried out, in collaboration with the group of the SAPHIR experimental facility at LOA (Laboratoire d'Optique Appliquee) in Paris using a 200 TW Ti:Sapphire laser system. During this campaign a deep study of the quadrupole system optics has been performed, comparing the results with the simulation codes used to determine the setup of the PMQ system and to track protons with realistic TNSA-like divergence and spectrum. Experimental and simulation results are good agreement, demonstrating the possibility to have a good control on the magnet optics. The procedure used during the experimental campaign and the most relevant results are reported here.

Nuclear fragmentation measurements are necessary when using heavy-ion beams in hadrontherapy to predict the effects of the ion nuclear interactions within the human body. Moreover, they are also fundamental to validate and improve the Monte Carlo codes for their use in planning tumor treatments. Nowadays, a very limited set of carbon fragmentation cross sections are being measured, and in particular, to our knowledge, no double-differential fragmentation cross sections at intermediate energies are available in the literature. In this work, we have measured the double-differential cross sections and the angular distributions of the secondary fragments produced in the (12)C fragmentation at 62 A MeV on a thin carbon target. The experimental data have been used to benchmark the prediction capability of the Geant4 Monte Carlo code at intermediate energies, where it was never tested before. In particular, we have compared the experimental data with the predictions of two Geant4 nuclear reaction models: the Binary Light Ions Cascade and the Quantum Molecular Dynamic. From the comparison, it has been observed that the Binary Light Ions Cascade approximates the angular distributions of the fragment production cross sections better than the Quantum Molecular Dynamic model. However, the discrepancies observed between the experimental data and the Monte Carlo simulations lead to the conclusion that the prediction capability of both models needs to be improved at intermediate energies.

We have measured the properties of the secondary particles produced in the interaction of carbon ion beams with homogeneous targets, in order to reconstruct the profile of the dose delivered in an hadron therapy treatment. Our measurements have been done with a 80 MeV/u fully stripped carbon ion beam at the INFN Laboratori Nazionali del Sud (LNS), Catania, with a Poly-methyl methacrylate target (PMMA). Both the neutral and the charged component of the secondaries have been measured, the neutral component including prompt photons and s+-annihilation photons (γ-PET).

In this paper we describe a novel system for the tracking of charged particles, designed to achieve real-time imaging, large detection areas and high spatial resolution especially suitable for use in medical diagnostic. A prototype of this tracker, having a 20 × 20 cm2 sensitive area, consisting of two crossed ribbons of 500 11m square scintillating fibers has been developed. The track position information is extracted real time in an innovative way, using a reduced number of read-out channels to obtain very large detection area with enough moderate costs and complexity. The performances of the tracker have been investigated using both β sources and cosmic rays and finally with a 62 MeV proton beam.

One of the particular characteristics of diamond detectors is their fast charge collection time. This feature makes these detectors very attractive for timing measurements in both nuclear and particle physics experiments. The charge collection time in these detectors is of the order of a few hundred ps, therefore the timing performance depends greatly on the electronics readout of the detector. In this work we present comparative measurements made using a single crystal diamond detector and two different electronic readout chains. In particular, we used a charge sensitive amplifier (CSA) with a 100 MHz bandwidth and a voltage amplifier with a 2 GHz bandwidth. In order to evaluate the performance of the detector for charge signals generated by particles with energies below minimum ionizing, measurements were taken using 62 MeV proton beam at the INFN - Laboratori Nazionali del Sud. Another set of measurements was made with a 120 GeV proton beam at FNAL in order to evaluate the performance with MIP. The timing performance depends on the rise time of the signal and the Signal to Noise ratio. Both these characteristics are inversely related to the electronic readout bandwidth. The charge collection with the 62 MeV proton beam was about 130 Ke-. A SIN ratio of about 80 was obtained with the CSA, while the SIN ratio was approximately 4 with the 2 GHz broad-band amplifier. This resulted in a comparable time distribution value of around 70 ps RMS in both cases. However, charge collection is much smaller with minimum ionizing particles, and while it was possible to perform measurements with the CSA, with the broadband amplifier it was not possible to separate signals from the background noise. In this work we present and discuss the set-up used and the complete set of measurements, with final considerations regarding range of use to which these detector can be utilized.

Neutrons constitute an important component of the radiation environment in hadron therapy accelerators. Their energy distribution may span from thermal up to hundred of MeV. The characterization of these fields in terms of dosimetric or spectrometric quantities is crucial for either the patient protection or the facility design aspects. To date, the Extended Range Bonner Sphere Spectrometer (ERBSS) is the only instrument able to simultaneously determine all spectral components in such workplaces. With the aim of providing useful data to the scientific community involved in neutron measurements at hadron therapy facilities, a measurement campaign was carried out at the Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA) of INFN-LNS (Laboratori Nazionali del Sud), where a 62 AMeV carbon ion is available. The beam was directed towards a PMMA phantom, simulating the patient, and two neutron measurement points were established at 01 and 901 with respect to the

International audience; 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.

Proton therapy is a highly precise form of cancer treatment, which requires accurate knowledge of the dose delivered to the patient and verification of the correct patient position to avoid damage to critical normal tissues. The development of pCT (proton Computed Tomography) system represents an important feature for precise proton radiation treatment planning because it could permit the direct measurement of the proton stopping power distribution, improving the accuracy in dose calculus, and the patient's position. A pCT prototype was manufactured in order to demonstrate the capability to acquire, during treatments in proton therapy centers, radiographic and tomographic images according to clinical demands.

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., This work has been supported by the European Community FP7 - Capacities, contract ENSAR n° 262010. This work was also supported by Junta de Andalucia and the Spanish Ministerio de Ciencia e Innovacion Contracts P07-FQM-02894, FIS2008-04189 and FPA2008-04972-C03.

In the research field of emergency dosimeters to be used in case of accidental radiation exposure of the population, watch glass has been considered as a possible fortuitous dosimetric material. This paper reports on results obtained by thermoluminescence of glass samples exposed to neutron and proton beams. Thermoluminescent glow curves have been analyzed for each irradiation studying the modifications induced by the irradiation as a function of proton dose or neutron fluence. The glow curve in a specific temperature range has been used as dosimetric parameter. The thermoluminescence response of samples exposed to protons has been found to be linear in the dose range between 2 and 20 Gy and the lowest detectable dose for this radiation beam is estimated to be smaller than than 1 Gy. In case of exposure with thermal neutrons the TL signal linearly increases with neutron fluence (up to about 3 × 1011 cm-2) and the lowest detectable fluence has been found to be of the order of magnitude of 109 cm-2. These results could be of interest for accidental retrospective dosimetry. © 2012 Elsevier B.V. All rights reserved.

Following previous work, we investigated in more detail the relationship between apoptosis and delayed luminescence (DL) in human leukemia Jurkat T cells under a wide variety of treatments. We used menadione and hydrogen peroxide to induce oxidative stress and two flavonoids, quercetin, and epigallocatechin gallate, applied alone or in combination with menadione or H2O2. 62 MeV proton beams were used to irradiate cells under a uniform dose of 2 or 10 Gy, respectively. We assessed apoptosis, cell cycle distributions, and DL. Menadione, H2O2and quercetin were potent inducers of apoptosis and DL inhibitors. Quercetin decreased clonogenic survival and the NAD(P)H level in a dose-dependent manner. Proton irradiation with 2 Gy but not 10 Gy increased the apoptotic rate. However, both doses induced a substantial G2/M arrest. Quercetin reduced apoptosis and prolonged the G2/M arrest induced by radiation. DL spectroscopy indicated that proton irradiation disrupted the electron flow within Complex I of the mitochondrial respiratory chain, thus explaining the massive necrosis induced by 10 Gy of protons and also suggested an equivalent action of menadione and quercetin at the level of the Fe/S center N2, which may be mediated by their binding to a common site within Complex I, probably the rotenone-binding site.

KENTROS (Kinetic ENergy and Time Resolution Optimized on Scintillator) is a relatively compact detector that 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.

Open Access.-- et al., 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)., This work has been supported by the European Community FP7 - Capacities, contract ENSAR nº 262010. This work was also supported by Junta de Andalucia and the Spanish Ministerio de Ciencia e Innovacion Contracts P07-FQM-02894, FIS2008-04189 and FPA2008-04972-C03.

International audience; 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.

A system of permanent magnet quadrupoles (PMQs) is going to be realized by INFN-LNS to be used as a collection system for the injection of laser driven ion beams up to 60 MeV/u in an energy selector based on four resistive dipoles. This system is the first element of the ELIMED (ELI-Beamlines MEDical and Multidisciplinary applications) beam transport, dosimetry and irradiation line that will be developed by INFN-LNS (It) and installed at the ELI-Beamlines facility in Prague (Cz). ELIMED will be the first user's open transport beam-line where a controlled laser-driven ion beam will be used for multidisciplinary researches. The definition of well specified characteristics, both in terms of performances and field quality, of the magnetic lenses is crucial for the system realization, for the accurate study of the beam dynamics and for the proper matching with the magnetic selection system which will be designed in the next months. Here, we report the design of the collection system and the adopted solutions in order to realize a robust system form the magnetic point of view. Moreover, the first preliminary transport simulations are also described.

The measurements performed using a fully stripped carbon ions beam of 80MeV/u impinging on a Poly-methyl methacrylate (PMMA) phantom at the Laboratori Nazionali del Sud (LNS) dell'INFN in Catania, Italy, are shown. The study of the neutral particles production from the fragmentation of the Carbon Projectiles plays a crucial role in the present development and delivery of therapeutical beams for hadron therapy. Measurements performed monitoring PMMA phantoms are fundamental to validate MC simulations and confirm expected performances of detectors used for monitoring purposes. The feasibility of online dose monitoring has been investigated using LYSO detectors for prompt photons and NaI crystals for β+ decays.

After nine years of activity, about 220 patients have been treated at the CATANA Eye Protontherapy facility. A 62MeV proton beam produced by a Superconducting Cyclotron is dedicated to radiotherapy of eye lesions, as uveal melanomas. Research and development work has been done to test different dosimetry devices to be used for reference and relative dosimetry, in order to achieve dose delivering accuracy. The follow-up results demonstrated the efficacy of proton beams and encouraged us in our activity in the fight against cancer.

A new version of a 1200V-20A MOS-GTO with 0.4 cm2 die area is presented. The improvements of the switching performances have been achieved thanks to a new He irradiation technique performed from the back side of the device in order to avoid the degradation of the surface gate oxide. The high energy He irradiation allowed us to kill the lifetime in proximity of the N−/N+ interface in such a way to significantly improve the device switching performances as suggested by the simulations. The irradiation did not affect the on-state characteristics. Instead, a reduction by a factor ∼4 in the storage time and more than 30% decrease in the turn-off energy losses have been measured on irradiated samples with respect to not irradiated ones.

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.

It is well established that high-LET radiations efficiently induce chromosome aberrations. However, data on the effect of protons on telomere maintenance, as involved in genomic stability, are scarce and contradictory. Here we demonstrate that high-LET protons induce telomere lengthening in human primary fibroblasts and that this elongation does not involve the telomerase enzyme, supporting the hypothesis that high-LET radiations are able to activate a telomerase-independent mechanism. In tumor cells that lack telomerase, one or more non-telomerase mechanisms for telomere maintenance are present, which are termed alternative lengthening of telomeres (ALT). Since ALT cells are characterized by recombinational events at telomeres, known as telomeric-sister chromatid exchanges (T-SCE), and colocalization of telomeres and premyelocytic leukemia protein (PML), we analyzed both T-SCE and PML. Our results show that high-LET protons induce a 2.5-fold increase of T-SCE and a colocalization of PML protein and telomeric DNA. Furthermore, our data show that the ALT pathway can be activated in human primary cells after induction of severe DNA damage. Thus, since telomeres are known to be involved in chromosome maintenance, the present work may contribute in the elucidation of the mechanism by which ionizing radiation induces genomic instability.

Background: Metastatic melanoma is one of the most aggressive tumours and is also very resistant to current therapeutic approaches. The aim of this investigation was the in vitro study of the anti-proliferative effects of fotemustine (FM; 100 and 250 µM), bevacizumab (5 µg/ml) and proton irradiation (12 and 16 Gy) on resistant HTB140 human melanoma cells. Methods: Viability was estimated by sulphorhodamine B assay, while cell proliferation was analyzed by 5-bromo-2-deoxyuridine assay. Cell cycle distribution and apoptosis were examined using flow cytometry. Results: Cell viability and proliferation were reduced after all applied treatments. The level of apoptosis significantly increased after treatment with FM, protons or a combination of all agents, while the apoptotic index ranged from 1.2 to 9.2. Proton irradiation, as well as combined treatment with bevacizumab and protons or 100 µM FM, bevacizumab and protons, have reduced melanoma cell proliferation through the induction of G1 phase arrest. Single FM (250 µM) or bevacizumab treatment and their combination, as well as the joint application of these 2 agents with protons, reduced cell proliferation and provoked G2 phase accumulation. Conclusion: The analyzed treatments reduced cell viability and proliferation, triggered G1 or G2 cell cycle phase accumulation and stimulated apoptotic cell death.

Ion treatment can deliver an accurate and effective therapy. The verification of the delivered dose, after each irradiation, is an information that can improve the effectiveness of the complete treatment, if a comparison of the planned with the delivered dose is foreseen. A possible way to do this verification is measuring the beta+ emitters, like 11-C, 15-O, 10-C that are generated in irradiated tissues by nuclear reactions, by using a positron emission tomography (PET) system. We have realized a PET prototype based on two planar heads; each head is made up of a position sensitive photomultiplier coupled to a square matrix of same size of LYSO scintillating crystals (2x2x18 mm3 pixel dimensions for a total area of 5x5 cm2). A special resistive chain and a dedicated electronic board that performs signal amplification and digitization were realized. A 3D Maximum Likelihood Expectation Maximization reconstruction program that uses all of the collected lines-of-response was implemented. This prototype was tested at the INFN-LNS proton facility in Catania (Italy), where clinical treatment of ocular pathologies in patients is performed. In this paper we present: the results obtained for the range monitoring in monoenergetic and extended proton irradiations of homogeneous PMMA cylinders; the dependence on different density values and stoichiometry with inhomogeneous phantoms; the spatial relationship between the dose distribution and its PET image.

This paper describes the beam flux monitoring system that has been developed at the Superconducting Cyclotron at INFN-LNS (Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Catania, Italy) in order to monitor the beam parameters such as energy, flux, beam profile, for SEE (Single Event Effects) cross-sections determination and DD (Displacement Damage) studies. In order to have an accurate and continuous monitoring of beam parameters we have developed fully automatic dosimetry setup to be used during SEE (with heavy ions) and DD (with protons up to 60 MeV) tests of electronic devices and systems. The final goal of our activity is to demonstrate that the operation of such a system in air is not detrimental to the accuracy on controlling the beam profile, energy and fluence delivered onto the DUT (Device Under Test) surface, even with non relativistic heavy ions. We have tested our beam monitoring system with the “Reference SEU monitor” developed by ESA/ESTEC, the results are discussed here.

There is today a growing up interest in hadrons and light ions therapy for tumors treatment, and new projects are worldwide rising in this field. The main advantage in using these particles is the possibility of tightly shaping the radiation dose to the target volume, thanks to the peculiarities of their interaction with matter. Anyway, the spatial accuracy of proton therapy is presently limited by the uncertainty in stopping power distribution, which is calculated from the photon attenuation coefficients measured by X-ray tomography. This uncertainty could be reduced by directly measuring stopping powers with a proton beam. The main problem is that protons do not move along straight lines across the medium, because of multiple Coulomb scattering; single proton tracking is a promising way to collect as much as possible information in order to circumvent this difficulty. The goals of this project, supported by INFN (PRoton IMAgin experiment) and MIUR (PRIN 2006), are: a) to develop a proton computed radiography (pCR) prototype capable to carry out a single projection; b) to validate the prototype with pre-clinical studies; c) to conceive a configuration for a complete proton computed tomography (pCT) system. Our target is to detect protons with initial kinetic energy high enough to traverse a human thorso (250-270 MeV) with a particle rate of ~1MHz, in order to collect data within a time of the order of 1s, suitable to clinical demands. Trajectory parameters to be measured are entrance and exit angle, entrance and exit position in the cross plane and residual energy. These data could be used, for instance, as input of most-likely path calculations to carry out a mapping of tissue electron density ρe. The final pCT system should be able to measure electron density with an accuracy better than 1% and with a spatial resolution better than 1 mm. Following earlier studies we designed the system described in fig.1, whose construction is presently under way. The tracker is composed of 4 x-y planes (p1-p4) capable to measure x-y coordinates of particle trajectory. A possible particle path (a) is indicated as an example. Planes p1 and p2 measure entrance angle and position, the object under study is placed in the gap between planes 2 and 3; planes p3 and p4 measure exit angle and position. An additional plane (p5) is included in the architecture for phantom testing purposes. As an example, in the figure, plane p5 is placed within a phantom composed of many planar slabs (c). In real applications the phantom will be replaced by the patient. The distance D between entrance (or exit) planes is about 1cm. x-y planes are composed of two tracker modules, including two printed circuit boards each: a "front end" board, which carries a Si detector and its readout ASICs, and a "digital board," mounted piggyback to the former, with FPGA-based digital electronics. One of the two modules within the same x-y plane is flipped upside down and rotated by 90° with respect to the other, to measure both the x and y local trajectory coordinates. The detector is a 256-channels silicon microstrip sensor

Due to the features of modern radiotherapy techniques, such as Intensity Modulated Radiation Therapy (IMRT), Stereotactic Treatments with photons and proton therapy, where high spatial dose gradient are often present, detectors to be employed for two-dimensional dose verifications must satisfy narrow requirements. In particular, they have to exhibit high spatial resolution. For these applications, in the framework of the European Integrated project MAESTRO (LSHC-CT-2004-503564) and of the INFN experiment PRIMA, we designed a modular system based on a monolithic silicon segmented sensor. A single sensor has been coupled with readout electronics and tested with satisfactory results by using 6, 10 and 25MV X-rays from a LINAC at the University Hospital of Florence and 62MeV protons at INFN LNS Catania, following MAESTRO procedures. For photons, almost all the channels exhibit performances within project specifications (repeatability ≪0.5%, reproducibility ≪1%, deviation from linearity ≪1%, dose rate dependence ≪1%). For protons, the measured Spread Out Bragg Peak is in good agreement with the one measured with a single diode and the detector shows also a good linearity in the range 20–5000 cGy. The output factors are in agreement with those measured with ionization chamber, single diode or film, within experimental errors.

High energy protons represent a very promising alternative in the tumor irradiation, as respect the photon and electron beams. In Italy, the first and at present the only proton-therapy facility, CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate), was built in Catania, at the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud (INFN-LNS). Here a 62 MeV proton beam, produced by a Superconducting Cyclotron (SC), is used for the treatment of shallow tumors like those of the ocular region. A beam monitoring system, based on ion chambers for dose monitoring and on silicon diodes scanning the beam cross section for the beam quality control. Moreover, gaf-chromic films are used to measure the geometric features of the beams. Even though these systems are stable and reliable, nevertheless they are time consuming and, in the gas-chromic film case, they require an off-line analysis. In this paper we present a feasibility study for using a silicon pixel detector as device for proton beams imaging and characterization. We present the performance of such a device exposed to the CATANA proton beam in terms of dose, dose rate and exposure time response.

The present work concerns non-destructive ion beam analysis carried out by means of proton-beam-induced nuclear reactions in the 10–30 MeV energy range. We focused our attention on the yield distribution of the isotopes produced in the internal region of a metal alloy. This distribution, which defines the analytical region, displays, at incident energy of about 20 MeV in a bronze based alloy, a bell-shaped curve centred at about 600 μm with an average width of about 400 μm. By changing the incident proton energy it is possible to displace the above region in the interior of the metal body. It should be pointed out that if we neglect to take into account the correct behaviour of the isotope yield distribution in samples with surface inhomogeneities we can obtain erroneous analytical results. We describe some experiments based on proton activation analysis (PAA) carried out at the INFN-Laboratori Nazionali del Sud (LNS) in Catania where we verified the bell-shape of the radioactive isotope distribution. The resulting formulas are given for quantitative analysis. It is straightforward that, by choosing the appropriate incident proton energy, it is possible to confine the whole analytical region to the interior of the body, thus eliminating any influence of surface effects. We have called this particular approach deep proton activation analysis (DPAA). Examples of its use on archaeological artefacts are given.

Proton therapy is a precise forms of radiation therapy that makes use of high energy proton compared to the conventional, more commonly used and less precise x-ray and electron beams. On the other hand, to fully exploit the proton therapy advantages, very accurate quality controls of the treatments are required. These are mainly related to the dose calculations and treatment planning. Actually dose calculations are routinely performed on the basis of X-ray computed tomography while a big improvement could be obtained with the direct use of protons as the imaging system. In this work we report the results of Monte Carlo simulations for the study of an imaging system based on the use of high energy protons: the proton computed tomography (pCT). The main limitation of the pCT and the current adopted technical solutions, based on the use of the most likely path (MLP) approximation are illustrated. Simulation results are compared with experimental data obtained with a first prototype of pCT system tested with 200 MeV proton beams available at the Loma Linda University Medical Center (LLUMC) (CA).