Design and Status of the ELIMED Beam Line for Laser-Driven Ion Beams

Charged particle acceleration using ultra-intense and ultra-short laser pulses has gathered a strong interest in the scientific community and it is now one of the most attractive topics in the relativistic laser-plasma interaction research. Indeed, it could represent the future of particle acceleration and open new scenarios in multidisciplinary fields, in particular, medical applications. One of the biggest challenges consists of using, in a future perspective, high intensity laser-target interaction to generate high-energy ions for therapeutic purposes, eventually replacing the old paradigm of acceleration, characterized by huge and complex machines. The peculiarities of laser-driven beams led to develop new strategies and advanced techniques for transport, diagnostics and dosimetry of the accelerated particles, due to the wide energy spread, the angular divergence and the extremely intense pulses. In this framework, the realization of the ELIMED (ELI-Beamlines MEDical applications) beamline, developed by INFN-LNS (Catania, Italy) and installed in 2017 as a part of the ELIMAIA beamline at the ELI-Beamlines (Extreme Light Infrastructure Beamlines) facility in Prague, has the aim to investigate the feasibility of using laser-driven ion beams in multidisciplinary applications. ELIMED will represent the first user's open transport beam line where a controlled laser-driven ion beam will be used for multidisciplinary and medical studies. In this paper, an overview of the beamline, with a detailed description of the main transport elements, will be presented. Moreover, a description of the detectors dedicated to diagnostics and dosimetry will be reported, with some preliminary results obtained both with accelerator-driven and laser-driven beams

Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications

Background: There is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect observed in FLASH radiotherapy, where particles are delivered at 40-1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 10^9 Gy/s, and predicted oxygen depletion effects on cellular response can be tested. Access to appropriate experimental environments, allowing measurements under controlled oxygenation conditions, is a key requirement for these studies. We report on the development and application of a bespoke portable hypoxia chamber specifically designed for experiments employing laser-driven sources, but also suitable for comparator studies under FLASH and conventional irradiation conditions. Materials and Methods: We used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (AG01522B) and patient-derived glioblastoma (E2) cancer stem cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival exposed to cyclotron-accelerated protons and X-rays in the normal fibroblast and radioresistant GBM stem cells. Results: Oxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 minutes and pathological hypoxia for up to 24 hrs after disconnecting the chambers from the gas supply. We observed a significant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 minutes post-irradiation. Under hypoxic irradiations, the Laser-driven protons induced significant residual DNA DSB damage in hypoxic AG01522 cells compared to the conventional dose rate protons suggesting an important impact of these extreme high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.108 and 2.501 ±0.125 respectively for the AG01522 and patient derived GBM stem cells for the X-rays using our hypoxia chambers for irradiation. Conclusion:We demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after laser-driven protons at ultra-high dose, conventional protons and X-ray exposures. Good levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects and the data obtained provided an indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays

Clinical and Research Activities at the CATANA Facility of INFN-LNS: From the Conventional Hadrontherapy to the Laser-Driven Approach

The CATANA proton therapy center was the first Italian clinical facility making use of energetic (62 MeV) proton beams for the radioactive treatment of solid tumors. Since the date of the first patient treatment in 2002, 294 patients have been successful treated whose majority was affected by choroidal and iris melanomas. In this paper, we report on the current clinical and physical status of the CATANA facility describing the last dosimetric studies and reporting on the last patient follow-up results. The last part of the paper is dedicated to the description of the INFN-LNS ongoing activities on the realization of a beamline for the transport of laser-accelerated ion beams for future applications. The ELIMED (ELI-Beamlines MEDical and multidisciplinary applications) project is introduced and the main scientific aspects will be described

TOF-based diagnostics system development and Geant4 simulation of the ELIMED transport and dosimetry beam line for high energy laser-driven ion beam applications @ ELI Beamlines

The acceleration processes based on the coherent interaction of high-power laser with matter is by now one of the most interesting topics in the field of particle acceleration, becoming a real alternative to conventional approaches. Some of the peculiarities of laser accelerated ion beams, if well controlled, are very promising for fundamental research as well as for multidisciplinary applications, including the medical field. In this framework, a complete transport and dosimetry beam line, named ELIMED, has been realized at INFN-LNS and will be installed at ELI-Beamlines by the end of 2017. It will be a section of the user-oriented ELIMAIA (ELI Multidisciplinary Applications of laser-Ion Acceleration) beam line at ELI-Beamlines, dedicated to the high-energy ion acceleration as well as high-intense X-rays generation and their possible multidisciplinary applications. The present thesis describes the Monte Carlo Geant4-based application, simulating the complete ELIMED beam line, in terms of geometry as well as magnetic and electric fields. Realistic top-to-bottom simulations have been performed to predict beam parameters and optimize dose distributions at the irradiation point in terms of homogeneity and dose delivered per shot in view of medical applications. In particular, the simulation performed clearly indicates the possibility to obtain a Spread Out Bragg Peak (SOBP) of clinical relevance with the selected proton beams. A specific on-line diagnostics system based on the Time Of Flight (TOF) technique coupled with diamond and/or silicon carbide detectors, has been developed and will be used for shot-to-shot energy distribution and flux measurement. Considering the high-energy laser-driven ion beams that will be delivered at ELIMAIA, a new analysis procedure, optimized for high-energy laser-driven proton beams, to extract the energy distribution for a given in species from the TOF signal has been developed and validated. The experiments carried out in the multi-TW laser facilities, Rutherford Appleton Laboratory (RAL, UK), Ludwig Maximilians University Munchen (LMU, GE) and the Prague Asterix Laser System (PALS,CZ), will be described in details together with the results achieved using the TOF method for beam diagnostics. The results confirmed the reliability of the TOF technique and of the procedure developed for high-energy laser-driven ion beams, pointing out that TOF technique can be particularly suitable for the on-line diagnosis of the high-energy ion beam characteristics, giving real time information useful to optimize transport as well as to investigate specific nuclear reactions occuring in the laser-target interaction

A new energy spectrum reconstruction method for time-of-flight diagnostics of high-energy laser-driven protons

Data containing the TOF signals and the energy spectra reconstructed with the method explained in the paper 'A new energy spectrum reconstruction method for time-of-flight diagnostics of high-energy laser-driven protons

TOF diagnosis of laser accelerated, high-energy protons

Data presented in the paper 'TOF diagnosis of laser accelerated, high-energy protons'. TOF signals acquired during the experiment described in the paper and proton energy spectra obtained on the rear and front side of the target. Comparison with RCF stacks and a Thomson Parabola Spectrometer (TP) coupled with Image Plate (IP) for validation are also reported

Configuration self-repair in Xilinx FPGAs

The usage of static random access memory-based field programmable gate arrays (FPGAs) on high-energy physics detectors is mostly limited by the sensitivity of devices to radiation-induced upsets in their configuration. In this paper, we describe a scrubber core designed for Xilinx FPGAs, based on configuration redundancy. When no upsets happen in homologous redundant bits and the scrubber is functional, the adopted redundancy makes it possible to correct all the errors. In fact, the scrubber corrects its own configuration and the one pertaining to a given user design. We discuss the architecture and two implementations of the scrubber, corresponding to different flavors of triple modular redundancy. We report results from proton irradiation tests, which prove that our core can extend the lifetime of a benchmark circuit up to 290%

Redundant-Configuration Scrubbing of SRAM-Based FPGAs

Static RAM-based field programmable gate arrays (SRAM-based FPGAs) are widely adopted in trigger and data acquisition systems of high-energy physics detectors for imple-menting fast logic due to their reconfigurability, large real-time processing capabilities and embedded high-speed serial IOs. These devices are sensitive to radiation-induced upsets, which may alter the functionality of the implemented circuit. Presently, their usage on-detector is limited and there is a strong interest in finding solutions for improving their tolerance to radiation-induced upsets. In this paper, we show a novel configuration-redundancy generation and scrubbing technique for SRAM-based FPGAs. It leads to a power saving with respect to other solutions in the literature. Moreover, our technique is compatible with several Xilinx FPGA families. Our solution does not require neither the usage of external memories nor third-party layout tools. We describe an example of our solution applied to a benchmark design implemented in a Xilinx Kintex-7 FPGA. In order to prove the effectiveness of the solution, we present results from a proton irradiation test