ABSTRACT The first proton linear accelerator for tumor therapy based on an actively scanned beam up to the energy of 150 MeV, is under development and construction by ENEA-Frascati, ISS and IFO, under the Italian TOP-IMPLART project. Protons up to the energy of 7 MeV are generated by a customized commercial injector operating at 425 MHz; currently three accelerating modules allow proton delivery with energy up to 27 MeV. Beam homogeneity and reproducibility were studied using a 2D ionizing chamber, EBT3 films, a silicon diode, MOSFETs, LiF crystals and alanine dosimetry systems. Measurements were taken in air with the detectors at ~1 m from the beam line exit window. The maximum energy impinging on the detectors surface was 24.1 MeV, an energy suitable for radiobiological studies. Results showed beam reproducibility within 5% and homogeneity within 4%, on a circular surface of 16 mm in diameter. INTRODUCTION The recognized advantages of proton therapy for the treatment of specific tumors have driven a rapid increase in the number of proton therapy centers. In Italy, there are three proton centers: the National Center of Oncological Hadrontherapy, Pavia (CNAO), the Proton Therapy Center (PTC) at Trento Hospital, both for the treatment of deep tumors, and the CATANA Center, in Catania, devoted to eye melanoma with protons up to 60 MeV. The first proton linear accelerator dedicated to cancer therapy is currently under construction in the framework of the Oncological Therapy with Protons (TOP)-Intensity Modulated Proton Linear Accelerator for Radiotherapy (IMPLART) project, which involves the Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA-Frascati), in collaboration with the Italian National Institute of Health (ISS), and Regina Elena National Cancer Institute (IFO). The TOP-IMPLART project intends to develop and construct a compact, modular proton linear accelerator devoted to tumor treatments based on an actively scanned beam up to the final energy of 150 MeV. Further funding will allow the final energy of 230 MeV to be reached. The accelerator is now under construction at ENEA-Frascati, which was chosen as the test site before moving the machine to a clinical environment. Protons up to the energy of 7 MeV are generated by a commercial injector operating at 425 MHz followed by a sequence of 3 GHz accelerators grouped into modules releasing the beam along a horizontal line. A deflecting magnet placed after the injector can deliver the proton beam to a vertical beam-line dedicated to radiobiology experiments. Currently, the beam line consists of three accelerating modules that allow the delivery of protons with energy ranging from 18 to 27 MeV. The beam current varies from 0.5 to 35 μA and it is characterized by pulse duration of 3 μs and a repetition frequency of 10 Hz. The peculiar time and intensity structure of the beam pulses of the linear accelerator, and their low emittance, offer the possibility of an optimal active dose delivery to the patient, in terms of ballistic precision following organ motion; accurate dose calibration procedures and methods are of primary importance to achieve it. Due to low energy, the beam is not yet suitable for therapy. In addition, no scanning system has been implemented yet to have the beam laterally spread. This article presents a preliminary dosimetric characterization of the passive lateral spread spot to be used for radiobiological studies. The entire experiment was conducted using pristine beam. Several dosimetry systems: a 2D ionizing chamber (IC), EBT3 Gafchromic films, a silicon diode, MOSFET detectors, nominally pure LiF crystals and alanine dosemeters were used to characterize the 27 MeV nominal proton beam in terms of homogeneity and reproducibility of the single spot. An extensive dosimetric characterization of the beam is in progress(1). MATERIALS AND METHODS Detectors 2D ionization chamber The 2D ionizing chamber was developed at the ISS as prototype for the dose delivery monitor. It is made of highly segmented cathode that exploits the micro-pattern technology. The chamber, with a water equivalent thickness of 0.17 mm, measures the single beam pulse intensity profiles simultaneously along x and y axes with spatial resolution better than 0.8 mm and sensitivity of 100 fC. A large dynamic range (>104) is obtained by a specialized electronics that automatically adapts the gain on each segment (channel) according to the amount of collected charge which is proportional to the intensity of the beam(2). In all irradiations, the 2D IC was kept in front of the other dosemeters at a distance of ~15 cm. The energy of the 27 MeV proton beam is reduced by ~0.55 ± 0.05 MeV traversing the IC. EBT3 Gafchromic film EBT3 Gafchromic films, coming from the same lot, were used specifically for beam homogeneity study. They have a 0.028 mm thick active layer (sandwiched between two 0.125 mm thick layers of polyester)(3). Squared film pieces of ~20 × 20 mm2, suitable for a dedicated sample holder, were cut from 203.2 × 254.0 mm2 sheets. Film pieces of larger dimensions were employed, before starting each measurement session, to verify the position of the beam on the x–y plane. An EPSON Expression 10000XL/PRO color scanner in transmission mode was used to read the EBT3 films. All irradiations were done with the films placed perpendicularly to the incoming beam. MOSFET Mobile MOSFET system (Best Medical, Ottawa, Ontario, Canada) is a wireless dosimetry system based on MOSFET (Metal Oxide Silicon Field Effect Transistors). The small size of detectors (active area 0.1 mm2), makes them particularly suitable for point-like dose measurements. In this work MOSFET dosemeters model TN-520RDM (MicroMOSFET) were used. The system consists of remote monitoring dose verification software, wall-mounted Bluetooth wireless transceiver and a small reader module. The standard bias setting of the reader module was kept constant and the sensitivity was ~0.1 V/Gy. In this modality, MOSFET dosemeters have a lifetime of ~200 Gy. The variation due to the change in the voltage caused by irradiation is proportional to absorbed dose. In the present work, measurements were performed using up to five MOSFET dosemeters simultaneously(4). Silicon diode A high-doped p-type stereotactic field detector (Hi-pSi) mod. DEB050 produced by Scanditronix was used. The silicon (Si) diode sensitive material, 60 μm thick with a diameter of 0.60 ± 0.1 mm, is encapsulated in a waterproof material. The displacement from detector front surface of the effective point of measurement is of 0.61 ± 0.15 mm. The detector was connected to a Keithley electrometer mod. 6517 A with no polarizing voltage. Readings were corrected for leakage current. The diode was used with its axis both parallel and perpendicular to the beam axis. Alanine dosemeters Alanine pellets were purchased from Gamma-Service (Leipzig, Germany). They consist of a mixture of 96% by weight of alanine and 4% of undisclosed binder material. The pellets are cylindrically shaped with diameter of 4.8 ± 0.04 mm and height of 2.98 ± 0.04 mm, and the mass density is ~1.2 g/cm3. The combined uncertainty in alanine dose assessment was estimated in 1% (k = 1). Alanine measurements were carried out with a Bruker ELEXSYS (Karlsruhe, Germany) spectrometer operating in X-band and equipped with a high sensitive SHQ cavity. Details about the read out procedure have been described elsewhere(5). For irradiations, a dedicated holder was used to irradiate three alanine pellets simultaneously. LiF crystals The irradiated samples were rectangular pieces of 10 × 5 mm2, 1 mm thick of nominally pure LiF crystals polished on both faces, cut from squared pieces of 10 × 10 mm2, commercially available (MacroOptica Ltd., Russia). Proton irradiation caused the formation of stable aggregate color centers, which emit broad photoluminescence bands in the visible spectral range under optical pumping in the blue(6). In this experiment, the red photoluminescence of the F2 color centers, excited with a continuous wave laser at 445 nm, was spectrally filtered at 678 nm by a monochromator and acquired by means of a photomultiplier with lock-in technique. Alanine dosementers, LiF crystals and EBT3 films were calibrated in 60Co source at the Italian Primary Lab. Due to the extensive use of the diode in protons, the Si diode is no longer calibrated. MOSFET detectors were inter-calibrated using an ionization chamber calibrated in 60Co source at the Italian Primary Lab. As a first step, the 2D ionization chamber was calibrated against alanine in protons. Phantom and holders A polymethyl methacrylate (PMMA) phantom designed and made at the ISS was used. It consists of a 15 × 15 × 15 cm3 tank. On one side of the tank a removable square window of 3.5 × 3.5 cm2 allows to perform measurements in free air. For alanine, silicon diode and EBT3 film dedicated PMMA holders were manufactured (Figure 1). These holders allow the positioning of the dosemeters exactly at the center of the window by means of a track mounted inside the tank. Whereas, no holder was used for MOSFETs and LiF crystals which were positioned on the PMMA tank surface and on the alanine holder, respectively. Figure 1. View largeDownload slide PMMA phantom and holders used for measurements in protons. Figure 1. View largeDownload slide PMMA phantom and holders used for measurements in protons. Irradiations The linac operates in a pulsed mode: currently the temporal structure of the proton beam consists of a sequence of pulses with a width of 2.7 μs (FWHM) at a repetition frequency of 10 Hz. The proton beam exits in air through a 50 μm Ti window, and pass through an integral ionization chamber mounted right after the extraction segment. This chamber measures the output charge and is used during the irradiations to turn-off the beam when a preset amount of particle charge is reached. So the total dose delivered is not affected by eventual pulse by pulse instabilities(7). Irradiations for beam characterization were done in free air, placing the detectors at ~1 m from the beam pipe exit window (where the beam spot diameter is ~2 mm), in order to have a lateral spread of the beam suitable for radiobiological studies. The maximum energy impinging on the detectors surface inside the PMMA phantom was 24.1 MeV, as measured by photoluminescence of color centers in a LiF crystal irradiated in a specific geometry that ensured the complete absorption condition of the beam(8). As the proton range in the different materials was always higher than the detector thickness (sensitive and coating material), transmission conditions were ensured in the sensitive volume of each detector. RESULTS AND DISCUSSION Beam homogeneity was investigated using EBT3 Gafchromic films. Figure 2 reports the results obtained using the films inserted in the suitable holder. As the thickness of the holder (~11 mm) is higher than the range of the 24.1 MeV protons in PMMA, the same holder was used to collimate the beam. No specific effects are expected on the flatness and the penumbra of the field due to the presence of the collimator. Then beam homogeneity was evaluated inside the circular beam cross-section defined by the film holder. The diameter of this surface is 16 mm. As slight dose variations are expected over that area, an approximation of linear behavior of the EBT3 response was assumed. Then, homogeneity was evaluated as percentage coefficient of variation (CV%, standard deviation to the mean ratio, expressed in percentage units) of the net pixel value along several diameters drawn to different angles (0°, ±45°, 90°). For all measurements it was better of 4%. Figure 2 shows a difference among angles. It could be due to the asymmetry of the beam at the exit of the pipeline (elliptic shape) that probably is also kept up to the detector position. Figure 2. View largeDownload slide Homogeneity measurements obtained using EBT3 films. Beam homogeneity evaluated over the circular beam cross section of 16 mm in diameter bounded by the EBT3 holder; the measurements were performed at 1 m of distance from the beam line exit. Figure 2. View largeDownload slide Homogeneity measurements obtained using EBT3 films. Beam homogeneity evaluated over the circular beam cross section of 16 mm in diameter bounded by the EBT3 holder; the measurements were performed at 1 m of distance from the beam line exit. As for beam reproducibility, several measurement runs were performed with different dosemeters. In particular, in Table 1 the results of three measurement runs are reported in terms of the variation coefficient of the measurements. In the first measurement run the 2D IC and Si diode were simultaneously irradiated. The diode was housed in the dedicated holder and placed at the center of the spread beam with its axis parallel to the incoming protons. In this configuration 15 irradiations were repeated under the same conditions. Table 1. Reproducibility of the proton beam evaluated as the variation coefficient of the dosemeter response for repeated irradiations under the same conditions in three irradiation runs. In the last measurement run (third column) all the dosemeters were simultaneously irradiated. Detector CV% CV% CV% Run 1 Run 2 Run 3 IC 3.52% 4.08% 0.76% Si 2.96% 4.56% 2.82% MOSFET1 5.44% 1.29% MOSFET2 0.92% MOSFET3 2.98% MOSFET4 4.31% Alanine 1.24% LiF 2.29% Detector CV% CV% CV% Run 1 Run 2 Run 3 IC 3.52% 4.08% 0.76% Si 2.96% 4.56% 2.82% MOSFET1 5.44% 1.29% MOSFET2 0.92% MOSFET3 2.98% MOSFET4 4.31% Alanine 1.24% LiF 2.29% Table 1. Reproducibility of the proton beam evaluated as the variation coefficient of the dosemeter response for repeated irradiations under the same conditions in three irradiation runs. In the last measurement run (third column) all the dosemeters were simultaneously irradiated. Detector CV% CV% CV% Run 1 Run 2 Run 3 IC 3.52% 4.08% 0.76% Si 2.96% 4.56% 2.82% MOSFET1 5.44% 1.29% MOSFET2 0.92% MOSFET3 2.98% MOSFET4 4.31% Alanine 1.24% LiF 2.29% Detector CV% CV% CV% Run 1 Run 2 Run 3 IC 3.52% 4.08% 0.76% Si 2.96% 4.56% 2.82% MOSFET1 5.44% 1.29% MOSFET2 0.92% MOSFET3 2.98% MOSFET4 4.31% Alanine 1.24% LiF 2.29% After that, a MOSFET dosemeter was included in the successive measurement run. It was placed on the phantom window with its sensitive part as close as possible to the Si diode. In this configuration, four irradiations were repeated. As last step, spread beam reproducibility was investigated at different points of the x–y plane using all the dosemeters. In particular, three alanine pellets were placed in the dedicated holder, at the center of the beam; the same holder was also used for positioning the LiF crystal; the Si diode was moved to a corner of the window at the edge of the proton field, and three additional MOSFETs were placed at the remaining corners of the window (Figure 3). In this configuration, seven measurements were repeated. As alanine and LiF are passive dosemeters, after each irradiation both dosemeters were replaced with unirradiated ones. Figure 3. View largeDownload slide Arrangement of the dosemeters during the third irradiations: MOSFETs and Si diode all around the perimeter of window, alanine at the center and LiF crystal above alanine, 2D IC in front of the tank and integral IC at the exit of the pipeline. Figure 3. View largeDownload slide Arrangement of the dosemeters during the third irradiations: MOSFETs and Si diode all around the perimeter of window, alanine at the center and LiF crystal above alanine, 2D IC in front of the tank and integral IC at the exit of the pipeline. The variation coefficients of the signal of each detector in the repeated measurements are reported in Table 1 and show a reproducibility of the beam within 5%. In the first two runs, the CV% values show an agreement within 1.5% between 2D IC, Si diode and MOSFET1.These results seem to indicate a real instability of the beam that could be due to an incomplete warm-up of the accelerator. In the last run, a large variability among CV% of the different detectors can be observed. It could be explained taking into account both the reproducibility of the detectors (better than 1% for alanine, 2D IC and diode, within 3% for MOSFET and LiF crystals) and their positioning. Indeed, for MOSFET detectors and Si diode, accidental changes in their positioning were possible during the replacement of the alanine pellets and LiF crystals after each irradiation. In particular, MOSFET4 was actually thus affected. In addition, no specific housing had been built for LiF crystals, so small differences in crystal positioning for each irradiation were also possible. CONCLUSIONS In this work the 27 MeV proton beam produced by the TOP-IMPLART linear accelerator under construction in Italy was investigated in terms of homogeneity and reproducibility. The study shows that homogeneity was within 4% in a circular surface of 16 mm in diameter and reproducibility better than 5%. These findings are considered acceptable for radiobiological experiment, although a full dosimetric characterization of the beam is in progress. Funding This work was supported by Regione Lazio, Italy. REFERENCES 1 Ferrari, P., Vadrucci, M., Campani, L., Mariotti, F. and Picardi, L. Preliminary study of neutron field in TOP-IMPLART proton therapy beam. Radiat. Prot. Dosim. ( 2017). doi:10.1093/rpd/ncx225. 2 Basile, E. et al. . An online proton beam monitor for cancer therapy based on ionization chambers with micro pattern readout. J. Instrum. 7, C03020 ( 2012). Google Scholar CrossRef Search ADS 3 GAFChromic™ EBT3 Film Specifications. Available on www.gafchromic.com. 4 Soriani, A., Landoni, V., Marzi, S., Iaccarino, G., Saracino, B., Arcangeli, G. and Benassi, M. Setup verification and in vivo dosimetry during intraoperative radiation therapy (IORT) for prostate cancer. Med. Phys. 34( 8), 3205– 3210 ( 2007). Google Scholar CrossRef Search ADS PubMed 5 Onori, S., Bortolin, E., Calicchia, A., Carosi, A., De Angelis, C. and Grande, S. Use of commercial alanine and TL dosemeters for dosimetry intercomparison among Italian radiotherapy centres. Radiat. Prot. Dosim. 120, 226– 229 ( 2006). Google Scholar CrossRef Search ADS 6 Piccinini, M., Ambrosini, F., Ampollini, A., Carpanese, M., Picardi, L., Ronsivalle, C., Bonfigli, F., Libera, S., Vincenti, M. A. and Montereali, R. M. Solid state detectors based on point defects in lithium fluoride for advanced proton beam diagnostics. J. Lumin. 156, 170– 174 ( 2014). Google Scholar CrossRef Search ADS 7 Ronsivalle, C., Ampollini, A., Bazzano, G., Nenzi, P., Picardi, L., Surrenti, V., Trinca, E. and Vadrucci, M. The TOP-IMPLART linac: machine status and experimental activity. In: Proceedings of the Conference—8th International Particle Accelerator Conference (IPAC2017), Copenhagen, May 2017. pp. 4669–4672 ( 2017). 8 Piccinini, M. et al. . Proton beam spatial distribution and Bragg peak imaging by photoluminescence of color centers in lithium fluoride crystals at the TOP-IMPLART linear accelerator. Nucl. Instrum. Methods Phys. Res. A 872, 41– 51 ( 2017). Google Scholar CrossRef Search ADS © The Author(s) 2018. 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Radiation Protection Dosimetry – Oxford University Press
Published: Jan 29, 2018
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