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Background: Intra operative radiation therapy (IORT) is a cancer treatment modality combining surgery and radiation therapy that permits the delivery of a large single dose of radiation at the time of the tumour resection. During the last years, IORT has become a widespread technique in clinical routine. This was possible thanks to the recent development of small dedicated, and hence very flexible, electron accelerators suitable for a surgical operation environment. However, the electron beams produced by these dedicated linacs are different with respect to those produced by linacs used in conventional radiation therapy in terms of dose rate (dose delivered/time of irradiation), dose per pulse (dose delivered per emitted beam pulse) and energy spectrum. In particular the very high dose rate and dose per pulse (i.e., respectively about 20 and 100 times greater than those of conventional radiation therapy) pose some radiobiological questions that have not yet been fully investigated. The aim of this work was to evaluate the relative biological effectiveness (RBE) of the IORT beams through the experimental construction of dose-response curves for cell survival. Methods: Since breast cancer represents the elective malignancy for treatment by IORT, clonogenic survival was assayed in the MCF-7 cell line from breast tissue malignant adenocarcinoma as a function of dose for different dose rates (5, 25 and 75 Gy/min) and doses per pulse (4.2 and 7.4 cGy/pulse). Irradiations were performed at the IORT accelerator Novac7 (Hitesys SpA, Italy) delivering electrons at the nominal energy of 7 MeV. For comparison, irradiations were also carried out with a conventional radiotherapy accelerator (ClinacR DHX, Varian), providing a 6 MeV pulsed electron beam and 6 MV X-rays (dose rate and dose-per-pulse 2 Gy/min and 0.1 cGy/pulse respectively) as reference irradiations. Results: The IORT beam effectiveness was found almost the same with varying dose rate (5, 25 and 75 Gy/min) and dose per pulse (4.2 and 7.4 cGy/pulse). No significant difference was also found between IORT and conventional electron beams, while 6 MV X-rays (beam used in the conventional treatment of breast cancer) proved to be more effective. Conclusions: Data show that cell killing effectiveness of the electron beams from the IORT accelerator does not differ significantly from that of an electron beam used in conventional radiotherapy. This suggests that changes in the dose rate and dose per pulse, up to the values of 75 Gy/min and 7.4 cGy/pulse, do not affect the radiobiological characteristics of the beam. In the light of our results, new experimental data are needed to better compare the RBE of a IORT breast cancer treatment (5–9 MeV electron beams, 21 Gy at the 90% isodose level in single fraction) and the RBE of a conventional breast cancer treatment (6 MV X-rays, 2 Gy per fraction, 30 fractions).

The main direction proposed by the community of experts in the field of laser-driven ion acceleration is to improve particle beam features (maximum energy, charge, emittance, divergence, monochromaticity, shot-to-shot stability) in order to demonstrate reliable and compact approaches to be used for multidisciplinary applications, thus, in principle, reducing the overall cost of a laser-based facility compared to a conventional accelerator one and, at the same time, demonstrating innovative and more effective sample irradiation geometries. The mission of the laser-driven ion target area at ELI-Beamlines (Extreme Light Infrastructure) in Dolní Břežany, Czech Republic, called ELI Multidisciplinary Applications of laser-Ion Acceleration (ELIMAIA), is to provide stable, fully characterized and tuneable beams of particles accelerated by Petawatt-class lasers and to offer them to the user community for multidisciplinary applications. The ELIMAIA beamline has been designed and developed at the Institute of Physics of the Academy of Science of the Czech Republic (IoP-ASCR) in Prague and at the National Laboratories of Southern Italy of the National Institute for Nuclear Physics (LNS-INFN) in Catania (Italy). An international scientific network particularly interested in future applications of laser driven ions for hadrontherapy, ELI MEDical applications (ELIMED), has been established around the implementation of the ELIMAIA experimental system. The basic technology used for ELIMAIA research and development, along with envisioned parameters of such user beamline will be described and discussed.

An automated analysis system was developed that is able to scan nuclear track detectors CR-39. The system consists of an optical microscope, a CCD camera, a frame grabber and a personal computer. On the latter a software written in Labview language (version 7.1) is implemented to control the motion of the microscope stage, the autofocus function and to measure the geometric characteristics of particle tracks. The system is able to detect and measure couples of partially overlapped tracks. As a preliminary application of this system, we estimated the projectile total charge-changing cross section for a 1 GeV/n iron ion beam impacting a polyethylene target.

Space radiation represents one of the major health hazards to crews of interplanetary missions. As the duration of space flight increases, according to International Space Station (ISS) and Mars mission programs, the risk associated with exposure to ionizing radiation also increases. Although physical dosimetry is routinely performed in manned space missions, it is generally accepted that direct measurement of biological endpoints (biological dosimetry) is necessary for a precise assessment of radiation risk in extraterrestrial activities. Chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) are particularly suitable to this purpose, as they can provide estimates of both equivalent radiation dose and risk. In this study, cytogenetic analysis was performed on PBL chromosomes of an Italian astronaut involved in two different 10-day missions on the ISS (Marco Polo, April 2002, and ENEIDE, May 2005). Blood samples were collected before and after flights. CAs were evaluated in either mitotic spreads or in prematurely condensed chromosomes (PCC) by Fluorescence in Situ Hybridization (FISH). In addition, blood samples were exposed to graded doses of X-rays in vitro before and after the flight and cytogenetic damage evaluated to investigate whether the space environment alters the sensitivity of human cells to ionizing radiation. The yield of baseline chromosomal aberrations was not modified following Marco Polo and ENEIDE mission. This is consistent with the low dose absorbed in these short-term space missions. Preliminary results from Marco Polo mission suggested a significant increase in intrinsic radiosensitivity of lymphocytes after landing compared to pre-flight and follow-up (6 months after landing) samples. However, this effect was not observed during the ENEIDE mission. The results suggest that intra-indi-vidual variations in radiosensitivity are significant, but they cannot be related to the space flight.

A micro-Raman spectroscopy investigation has been performed in vitro on single human mammary epithelial cells after irradiation by graded x-ray doses. The analysis by principal component analysis (PCA) and interval-PCA (i-PCA) methods has allowed us to point out the small differences in the Raman spectra induced by irradiation. This experimental approach has enabled us to delineate radiation-induced changes in protein, nucleic acid, lipid, and carbohydrate content. In particular, the dose dependence of PCA and i-PCA components has been analyzed. Our results have confirmed that micro-Raman spectroscopy coupled to properly chosen data analysis methods is a very sensitive technique to detect early molecular changes at the single-cell level following exposure to ionizing radiation. This would help in developing innovative approaches to monitor radiation cancer radiotherapy outcome so as to reduce the overall radiation dose and minimize damage to the surrounding healthy cells, both aspects being of great importance in the field of radiation therapy.

Laser accelerated proton beams represent nowadays an attractive alternative to the conventional ones and they have been proposed in different research fields. In particular, the interest has been focused in the possibility of replacing conventional accelerating machines with laser-based accelerators in order to develop a new concept of hadrontherapy facilities, which could result more compact and less expensive. With this background the ELIMED (ELIMED: ELI-Beamlines MEDical applications) research project has been launched by LNS-INFN researchers (Laboratori Nazionali del Sud-Istituto Nazionale di Fisica Nucleare, Catania, IT) and ASCR-FZU researchers (Academy of Sciences of the Czech Republic-Fyzikalni ustar, Prague, Cz), within the pan-European ELI-Beamlines facility framework. Its main purposes are the demonstration of future applications in hadrontherapy of optically accelerated protons and the realization of a laser-accelerated ion transport beamline for multidisciplinary applications. Several challenges, starting from laser-target interaction and beam transport development, up to dosimetric and radiobiological issues, need to be overcome in order to reach the final goals. The design and the realization of a preliminary beam handling and dosimetric system and of an advanced spectrometer for high energy (multi-MeV) laser-accelerated ion beams will be shortly presented in this work.

Purpose The biological optimization of proton therapy can be achieved only through a detailed evaluation of relative biological effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate the RBE dependence on LET and intrinsic radiosensitvity. Methods and Materials Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). Results We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton biological effectiveness. Data were also used to validate a parameterized RBE model. Conclusions The predicted biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning.

ELI-Beamlines is one of the pillars of the pan-European project ELI (Extreme Light Infrastructure). It will be an ultra high-intensity, high repetition-rate, femtosecond laser facility whose main goal is generation and applications of high-brightness X-ray sources and accelerated charged particles in different fields. Particular care will be devoted to the potential applicability of laser-driven ion beams for medical treatments of tumors. Indeed, such kind of beams show very interesting peculiarities and, moreover, laser-driven based accelerators can really represent a competitive alternative to conventional machines since they are expected to be more compact in size and less expensive. The ELIMED project was launched thanks to a collaboration established between FZU-ASCR (ELI-Beamlines) and INFN-LNS researchers. Several European institutes have already shown a great interest in the project aiming to explore the possibility to use laser-driven ion (mostly proton) beams for several applications with a particular regard for medical ones. To reach the project goal several tasks need to be fulfilled, starting from the optimization of laser-target interaction to dosimetric studies at the irradiation point at the end of a proper designed transport beam-line. Researchers from LNS have already developed and successfully tested a high-dispersive power Thomson Parabola Spectrometer, which is the first prototype of a more performing device to be used within the ELIMED project. Also a Magnetic Selection System able to produce a small pencil beam out of a wide energy distribution of ions produced in laser-target interaction has been realized and some preliminary work for its testing and characterization is in progress. In this contribution the status of the project will be reported together with a short description of the of the features of device recently developed. Conference on Plasma Physics by Laser and Applications (PPLA), Oct 02-04, 2013, Univ Salento, Lecce, Italy

Laser accelerated proton beams have been proposed to be used in different research fields. A great interest has risen for the potential replacement of conventional accelerating machines with laser-based accelerators, and in particular for the development of new concepts of more compact and cheaper hadrontherapy centers. In this context the ELIMED (ELI MEDical applications) research project has been launched by INFN-LNS and ASCR-FZU researchers within the pan-European ELI-Beamlines facility framework. The ELIMED project aims to demonstrate the potential clinical applicability of optically accelerated proton beams and to realize a laser-accelerated ion transport beamline for multi-disciplinary user applications. In this framework the eye melanoma, as for instance the uveal melanoma normally treated with 62 MeV proton beams produced by standard accelerators, will be considered as a model system to demonstrate the potential clinical use of laser-driven protons in hadrontherapy, especially because of the limited constraints in terms of proton energy and irradiation geometry for this particular tumour treatment. Several challenges, starting from laser-target interaction and beam transport development up to dosimetry and radiobiology, need to be overcome in order to reach the ELIMED final goals. A crucial role will be played by the final design and realization of a transport beamline capable to provide ion beams with proper characteristics in terms of energy spectrum and angular distribution which will allow performing dosimetric tests and biological cell irradiation. A first prototype of the transport beamline has been already designed and other transport elements are under construction in order to perform a first experimental test with the TARANIS laser system by the end of 2013. A wide international collaboration among specialists of different disciplines like Physics, Biology, Chemistry, Medicine and medical doctors coming from Europe, Japan, and the US is growing up around the ELIMED project with the aim to work on the conceptual design, technical and experimental realization of this core beamline of the ELI Beamlines facility. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

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.

Micro-Raman technique can be particularly useful to investigate the chemical changes induced in structure, protein, nucleic acid, lipid, and carbohydrate contents of cells. The aim of this work is to inspect the possibility to employ Raman microspectroscopy to detect biochemical modifications in human mammary epithelial cells after exposure to different Xray doses. The samples consisted of cells cultured on polylysine-coated glass coverslips. After the exposition, control and treated cells were washed in phosphate-buffered saline (PBS) and then fixed in paraformaldehyde 3.7%. They were examined using a confocal micro-Raman system equipped with a He-Ne laser (λ = 632.8 nm; power on the sample= 3.5mW). Differences in the intensity ratio of specific Raman vibrational markers commonly assigned to phenylalanine and tyrosine amino acids (at 1000, 1030, 1618 cm -1 ), DNA bases (787, 1090, 1305 cm -1 ), and amide III (1237, and 1265 cm -1 ) with respect a reference peak (the one of lipids at 1450 cm -1 ) were evidenced between control and exposed cells. These differences may be indicative of damage in exposed cells as the fragmentation of individual amino acids and DNA bases, crosslink effects in molecular structure of DNA and protein conformational change that especially tend to "unwind" the protein due to the breaking of hydrogen bonds between peptide chains.

Shielding is the only practical countermeasure for the exposure to cosmic radiation during space travel. It is well known that light, hydrogenated materials, such as water and polyethylene, provide the best shielding against space radiation. Kevlar and Nextel are two materials of great interest for spacecraft shielding because of their known ability to protect human space infrastructures from meteoroids and debris. We measured the response to simulated heavy-ion cosmic radiation of these shielding materials and compared it to polyethylene, Lucite (PMMA), and aluminum. As proxy to galactic nuclei we used 1 GeV n iron or titanium ions. Both physics and biology tests were performed. The results show that Kevlar, which is rich in carbon atoms (about 50% in number), is an excellent space radiation shielding material. Physics tests show that its effectiveness is close (80-90%) to that of polyethylene, and biology data suggest that it can reduce the chromosomal damage more efficiently than PMMA. Nextel is less efficient as a radiation shield, and the expected reduction on dose is roughly half that provided by the same mass of polyethylene. Both Kevlar and Nextel are more effective than aluminum in the attenuation of heavy-ion dose.

Radiotherapy with high-energy carbon ion beams can be more advantageous compared to photons because of better physical dose distribution and higher biological efficiency in tumour cell sterilization. Despite enhanced normal tissue sparing, damage incurred by normal cells at the beam entrance is unavoidable and may affect the progeny of surviving cells in the form of inheritable cytogenetic alterations. Furthermore, the quality of the beam along the Bragg curve is modified by nuclear fragmentation of projectile and target nuclei in the body. We present an experimental approach based on the use of a polymethylmethacrylate (PMMA) phantom that allows the simultaneous exposure to a particle beam of several biological samples positioned at various depths along the beam path. The device was used to measure the biological effectiveness of a 60 MeV/amu carbon-ion beam at inducing chromosomal aberrations in G 0 -human peripheral blood lymphocytes. Chromosome spreads were obtained from prematurely condensed cells and all structural aberration types were scored in Fluorescence in situ Hybridization (FISH)-painted chromosomes 1 and 2. Our results show a marked increase with depth in the aberration frequency prior to the Bragg peak, which is consistent with a linear energy transfer (LET)-dependent increase in biological effectiveness.

Protons are the most abundant element in the galactic cosmic radiation, and the energy spectrum peaks around 1 GeV. Shielding of relativistic protons is therefore a key problem in the radiation protection strategy of crewmembers involved in long-term missions in deep space. Hydrogen ions were accelerated up to 1 GeV at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, New York. The proton beam was also shielded with thick ( about 20 g/cm(2)) blocks of lucite (PMMA) or aluminium ( Al). We found that the dose rate was increased 40-60% by the shielding and decreased as a function of the distance along the axis. Simulations using the General Purpose Particle and Heavy-Ion Transport code System (PHITS) show that the dose increase is mostly caused by secondary protons emitted by the target. The modified radiation Weld after the shield has been characterized for its biological eVectiveness by measuring chromosomal aberrations in human peripheral blood lymphocytes exposed just behind the shield block, or to the direct beam, in the dose range 0.53 Gy. Notwithstanding the increased dose per incident proton, the fraction of aberrant cells at the same dose in the sample position was not significantly modified by the shield. The PHITS code simulations show that, albeit secondary protons are slower than incident nuclei, the LET spectrum is still contained in the low-LET range (< 10 keV/mu m), which explains the approximately unitary value measured for the relative biological effectiveness.

ELI-Beamlines is one of the four pillars of the ELI (Extreme Light Infrastructure) pan-European project. It will be an ultrahigh-intensity, high repetition-rate, femtosecond laser facility whose main goals are the generation and applications of high-brightness X-ray sources and accelerated charged particles. In particular medical and multidisciplinary applications with laser-accelerated beams are treated by the ELIMED task force, a collaboration between different research institutes. A crucial goal for this network is represented by the design and the realization of a transport beamline able to provide ion beams with suitable characteristics in terms of energy spectrum and angular distribution in order to perform dosimetric tests and biological cell irradiations. A first prototype of transport beamline has been already designed and some magnetic elements are already under construction. In particular, an Energy Selector System (ESS) prototype has been already realized at LNS-INFN. This paper reports about the studies of the ESS properties as, for instance, energy spread and transmission efficiency, carried out using the GEANT4 Monte Carlo code.