A new model for volume recombination in plane-parallel chambers in pulsed fields of high dose-per-pulse.

In order to describe the volume recombination in a pulsed radiation field of high dose-per-pulse this study presents a numerical solution of a 1D transport model of the liberated charges in a plane-parallel ionization chamber. In addition, measurements were performed on an Advanced Markus ionization chamber in a pulsed electron beam to obtain suitable data to test the calculation. The experiment used radiation pulses of 4 µs duration and variable dose-per-pulse values up to about 1 Gy, as well as pulses of variable duration up to 308 [Formula: see text] at constant dose-per-pulse values between 85 mGy and 400 mGy. Those experimental data were compared to the developed numerical model and existing descriptions of volume recombination. At low collection voltages the observed dose-per-pulse dependence of volume recombination can be approximated by the existing theory using effective parameters. However, at high collection voltages large discrepancies are observed. The developed numerical model shows much better agreement with the observations and is able to replicate the observed behavior over the entire range of dose-per-pulse values and collection voltages. Using the developed numerical model, the differences between observation and existing theory are shown to be the result of a large fraction of the charge being collected as free electrons and the resultant distortion of the electric field inside the chamber. Furthermore, the numerical solution is able to calculate recombination losses for arbitrary pulse durations in good agreement with the experimental data, an aspect not covered by current theory. Overall, the presented numerical solution of the charge transport model should provide a more flexible tool to describe volume recombination for high dose-per-pulse values as well as for arbitrary pulse durations and repetition rates.

A light-weight compact proton gantry design with a novel dose delivery system for broad-energetic laser-accelerated beams.

Proton beams may provide superior dose-conformity in radiation therapy. However, the large sizes and costs limit the widespread use of proton therapy (PT). The recent progress in proton acceleration via high-power laser systems has made it a compelling alternative to conventional accelerators, as it could potentially reduce the overall size and cost of the PT facilities. However, the laser-accelerated beams exhibit different characteristics than conventionally accelerated beams, i.e. very intense proton bunches with large divergences and broad-energy spectra. For the application of laser-driven beams in PT, new solutions for beam transport, such as beam capture, integrated energy selection, beam shaping and delivery systems are required due to the specific beam parameters. The generation of these beams are limited by the low repetition rate of high-power lasers and this limitation would require alternative solutions for tumour irradiation which can efficiently utilize the available high proton fluence and broad-energy spectra per proton bunch to keep treatment times short. This demands new dose delivery system and irradiation field formation schemes. In this paper, we present a multi-functional light-weight and compact proton gantry design for laser-driven sources based on iron-less pulsed high-field magnets. This achromatic design includes improved beam capturing and energy selection systems, with a novel beam shaping and dose delivery system, so-called ELPIS. ELPIS system utilizes magnetic fields, instead of physical scatterers, for broadening the spot-size of broad-energetic beams while capable of simultaneously scanning them in lateral directions. To investigate the clinical feasibility of this gantry design, we conducted a treatment planning study with a 3D treatment planning system augmented for the pulsed beams with optimizable broad-energetic widths and selectable beam spot sizes. High quality treatment plans could be achieved with such unconventional beam parameters, deliverable via the presented gantry and ELPIS dose delivery system. The conventional PT gantries are huge and require large space for the gantry to rotate the beam around the patient, which could be reduced up to 4 times with the presented pulse powered gantry system. The further developments in the next generation petawatt laser systems and laser-targets are crucial to reach higher proton energies. However, if proton energies required for therapy applications are reached it could be possible in future to reduce the footprint of the PT facilities, without compromising on clinical standards.

Comparative investigation of three dose rate meters for their viability in pulsed radiation fields.

Pulsed radiation fields, characterized by microsecond pulse duration and correspondingly high pulse dose rates, are increasingly used in therapeutic, diagnostic and research applications. Yet, dose rate meters which are used to monitor radiation protection areas or to inspect radiation shielding are mostly designed, characterized and tested for continuous fields and show severe deficiencies in highly pulsed fields. Despite general awareness of the problem, knowledge of the specific limitations of individual instruments is very limited, complicating reliable measurements. We present here the results of testing three commercial dose rate meters, the RamION ionization chamber, the LB 1236-H proportional counter and the 6150AD-b scintillation counter, for their response in pulsed radiation fields of varied pulse dose and duration. Of these three the RamION proved reliable, operating in a pulsed radiation field within its specifications, while the other two instruments were only able to measure very limited pulse doses and pulse dose rates reliably.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors.

PURPOSE: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10(11) Gy∕s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. METHODS: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. RESULTS: The dosimeters are dose rate independent up to 4●10(9) Gy∕s within 2% (OSL and TLD) and up to 15●10(9) Gy∕s within 5% (EBT films). The diamond detectors show strong dose rate dependence. CONCLUSIONS: TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

A scintillator-based online detector for the angularly resolved measurement of laser-accelerated proton spectra.

In recent years, a new generation of high repetition rate (~10 Hz), high power (~100 TW) laser systems has stimulated intense research on laser-driven sources for fast protons. Considering experimental instrumentation, this development requires online diagnostics for protons to be added to the established offline detection tools such as solid state track detectors or radiochromic films. In this article, we present the design and characterization of a scintillator-based online detector that gives access to the angularly resolved proton distribution along one spatial dimension and resolves 10 different proton energy ranges. Conceived as an online detector for key parameters in laser-proton acceleration, such as the maximum proton energy and the angular distribution, the detector features a spatial resolution of ~1.3 mm and a spectral resolution better than 1.5 MeV for a maximum proton energy above 12 MeV in the current design. Regarding its areas of application, we consider the detector a useful complement to radiochromic films and Thomson parabola spectrometers, capable to give immediate feedback on the experimental performance. The detector was characterized at an electrostatic Van de Graaff tandetron accelerator and tested in a laser-proton acceleration experiment, proving its suitability as a diagnostic device for laser-accelerated protons.

FISH-based analysis of 10- and 25-kV soft X-ray-induced DNA damage in 184A1 human mammary epithelial cells.

Over the past years, several in vitro studies have been performed on DNA damage induced by soft X-rays, especially in the energy range below 50 keV. Radiation effects originating from such low-energy photons are relevant in the context of medical diagnostics, for example, mammography, or of accidental exposure to scattered radiation. The present study was initiated to investigate the X-ray energy-dependent induction of stable and unstable chromosomal aberrations in the human mammary epithelial cell line 184A1. Three colour fluorescence in situ hybridisation was applied to identify chromosomal damage in chromosomes 1, 8 and 17, induced by 10-kV or 25-kV soft X-rays as well as by 200-kV X-rays as a reference quality. The overall results confirm the X-ray energy dependencies published for human lymphocytes showing increasing chromosomal aberration frequencies and higher aberration complexity with decreasing X-ray energy and increasing dose. Comparing the obtained dose dependencies, ratios of 0.84 ± 0.09 and 1.22 ± 0.18 were revealed for stable translocations induced by 25- and 10-kV X-rays, respectively, using 200-kV X-rays as reference. Moreover, the analysis of the minimum number of breaks required to form the visible chromosomal damage resulted in similar ratios of 0.93 ± 0.07 for 25-kV X-rays and 1.25 ± 0.10 for 10-kV X-rays relative to 200-kV X-rays. In addition, non-DNA-proportional contributions of chromosomes 8 and 17 to the whole DNA damage and deviations from the expected 1:1 ratio of translocations and dicentrics were observed for cell line 184A1.

A dosimetric system for quantitative cell irradiation experiments with laser-accelerated protons.

An integrated dosimetry and cell irradiation system (IDOCIS) with laser-accelerated proton beams was developed, characterized, calibrated and successfully used for systematic in vitro experiments. Due to the broad exponentially shaped energy spectrum, the low-energy range of the protons (<20 MeV) and the high pulse dose, the absolute dosimetry for this beam quality is challenging. Therefore, a dedicated Faraday cup is used as an energy and dose rate independent absolute dosimeter that has been calibrated consistently with three independent methods. A transmission ionization chamber providing online relative dose information is cross-calibrated against the Faraday cup. Providing both online and absolute dose information, the IDOCIS allows for quantitative dosimetric and radiobiological studies at current low-energy laser-accelerated proton beams. Finally, first dosimetric characterizations of a laser-accelerated proton beam with the IDOCIS are presented.

Establishment of technical prerequisites for cell irradiation experiments with laser-accelerated electrons.

PURPOSE: In recent years, laser-based acceleration of charged particles has rapidly progressed and medical applications, e.g., in radiotherapy, might become feasible in the coming decade. Requirements are monoenergetic particle beams with long-term stable and reproducible properties as well as sufficient particle intensities and a controlled delivery of prescribed doses at the treatment site. Although conventional and laser-based particle accelerators will administer the same dose to the patient, their different time structures could result in different radiobiological properties. Therefore, the biological response to the ultrashort pulse durations and the resulting high peak dose rates of these particle beams have to be investigated. The technical prerequisites, i.e., a suitable cell irradiation setup and the precise dosimetric characterization of a laser-based particle accelerator, have to be realized in order to prepare systematic cell irradiation experiments. METHODS: The Jena titanium:sapphire laser system (JETI) was customized in preparation for cell irradiation experiments with laser-accelerated electrons. The delivered electron beam was optimized with regard to its spectrum, diameter, dose rate, and dose homogeneity. A custom-designed beam and dose monitoring system, consisting of a Roos ionization chamber, a Faraday cup, and EBT-1 dosimetry films, enables real-time monitoring of irradiation experiments and precise determination of the dose delivered to the cells. Finally, as proof-of-principle experiment cell samples were irradiated using this setup. RESULTS: Laser-accelerated electron beams, appropriate for in vitro radiobiological experiments, were generated with a laser shot frequency of 2.5 Hz and a pulse length of 80 fs. After laser acceleration in the helium gas jet, the electrons were filtered by a magnet, released from the vacuum target chamber, and propagated in air for a distance of 220 mm. Within this distance a lead collimator (aperture of 35 mm) was introduced, leading, along with the optimized setup, to a beam diameter of 35 mm, sufficient for the irradiation of common cell culture vessels. The corresponding maximum dose inhomogeneity over the beam spot was less than 10% for all irradiated samples. At cell position, the electrons posses a mean kinetic energy of 13.6 MeV, a bunch length of about 5 ps (FWHM), and a mean pulse dose of 1.6 mGy/bunch. Cross correlations show clear linear dependencies for the online recorded accumulated bunch charges, pulse doses, and pulse numbers on absolute doses determined with EBT-1 films. Hence, the established monitoring system is suitable for beam control and a dedicated dose delivery. Additionally, reasonable day-to-day stable and reproducible properties of the electron beam were achieved. CONCLUSIONS: Basic technical prerequisites for future cell irradiation experiments with ultrashort pulsed laser-accelerated electrons were established at the JETI laser system. The implemented online control system is suitable to compensate beam intensity fluctuations and the achieved accuracy of dose delivery to the cells is sufficient for radiobiological cell experiments. Hence, systematic in vitro cell irradiation experiments can be performed, being the first step toward clinical application of laser-accelerated particles. Further steps, including the transfer of the established methods to experiments on higher biological systems or to other laser-based particle accelerators, will be prepared.

Absolute charge calibration of scintillating screens for relativistic electron detection.

We report on new charge calibrations and linearity tests with high-dynamic range for eight different scintillating screens typically used for the detection of relativistic electrons from laser-plasma based acceleration schemes. The absolute charge calibration was done with picosecond electron bunches at the ELBE linear accelerator in Dresden. The lower detection limit in our setup for the most sensitive scintillating screen (KODAK Biomax MS) was 10 fC/mm(2). The screens showed a linear photon-to-charge dependency over several orders of magnitude. An onset of saturation effects starting around 10-100 pC/mm(2) was found for some of the screens. Additionally, a constant light source was employed as a luminosity reference to simplify the transfer of a one-time absolute calibration to different experimental setups.

Absolute response of Fuji imaging plate detectors to picosecond-electron bunches.

The characterization of the absolute number of electrons generated by laser wakefield acceleration often relies on absolutely calibrated FUJI imaging plates (IP), although their validity in the regime of extreme peak currents is untested. Here, we present an extensive study on the dependence of the sensitivity of BAS-SR and BAS-MS IP to picosecond electron bunches of varying charge of up to 60 pC, performed at the electron accelerator ELBE, making use of about three orders of magnitude of higher peak intensity than in prior studies. We demonstrate that the response of the IPs shows no saturation effect and that the BAS-SR IP sensitivity of 0.0081 photostimulated luminescence per electron number confirms surprisingly well data from previous works. However, the use of the identical readout system and handling procedures turned out to be crucial and, if unnoticed, may be an important error source.

First in-beam PET measurement of beta+ radioactivity induced by hard photon beams.

In this note, we present the first experimental results of in-beam PET measurements during high energy photon phantom irradiation. An inhomogeneous phantom was irradiated with pulsed 34 MV bremsstrahlung. The measurements have been conducted with a dedicated double head positron camera. A high material contrast could be achieved and furthermore production rates of (11)C and (15)O were derived from the time-dependent activity.

Quantification of beta+ activity generated by hard photons by means of PET.

Positron emission tomography (PET) as a method for quality assurance in radiotherapy is well investigated in the case of therapy with carbon ion beams and successfully applied at the Heavy Ion Medical Accelerator at Chiba (HIMAC), Japan, and the Gesellschaft für Schwerionenforschung (GSI), Germany. By measuring the beta(+) activity distribution during the irradiation (in-beam PET), valuable information on the precision of the dose deposition can be obtained. To extend this efficient technique to other radiation treatment modalities may be worthwhile. For example, since positron emitters are generated by high-energy photons with energies above 20 MeV due to (gamma, n) reactions (predominantly (11)C and (15)O in tissue), in-beam PET seems to be feasible for radiation therapy with high-energy photons as also shown in Geant4 simulations. Quantitative results on the activation of tissue-equivalent materials at hard photon beams were obtained by performing off-beam PET experiments. Homogeneous PMMA phantoms as well as inhomogeneous phantoms were irradiated with high-energy bremsstrahlung. After the irradiation the distributions of the generated positron emitters in the phantoms were measured using a conventional PET scanner. Furthermore, the depth-dose distributions were determined by means of optically stimulated luminescence detectors. In the experiments an activity per dose comparable to that produced in a typical patient irradiation with carbon ions could be achieved for 34 MV bremsstrahlung. In addition, a high contrast in the PET images for materials with different density and stoichiometry could be detected. Thus, further research concerning the development of in-beam PET seems to be worthwhile.

Dose quantification from in-beam positron emission tomography.

Positron emission tomography (PET) imaging of the radioactivity distributions induced by therapeutic irradiation is at present the only feasible method for an in situ and non-invasive monitoring of radiooncology treatments with ion beams. The clinical implementation of this imaging technology at the experimental carbon ion therapy facility at the Gesellschaft für Schwerionenforschung (GSI) at Darmstadt, Germany is outlined and an interactive approach for a PET guided quantification of local dose deviations with respect to the treatment plan is presented.

Washout measurement of radioisotope implanted by radioactive beams in the rabbit.

Washout of 10C and 11C implanted by radioactive beams in brain and thigh muscle of rabbits was studied. The biological washout effect in a living body is important in the range verification system or three-dimensional volume imaging in heavy ion therapy. Positron emitter beams were implanted in the rabbit and the annihilation gamma-rays were measured by an in situ positron camera which consisted of a pair of scintillation cameras set on either side of the target. The ROI (region of interest) was set as a two-dimensional position distribution and the time-activity curve of the ROI was measured. Experiments were done under two conditions: live and dead. By comparing the two sets of measurement data, it was deduced that there are at least three components in the washout process. Time-activity curves of both brain and thigh muscle were clearly explained by the three-component model analysis. The three components ratios (and washout half-lives) were 35% (2.0 s), 30% (140 s) and 35% (10 191 s) for brain and 30% (10 s), 19% (195 s) and 52% (3175 s) for thigh muscle. The washout effect must be taken into account for the verification of treatment plans by means of positron camera measurements.

Washout studies of 11C in rabbit thigh muscle implanted by secondary beams of HIMAC.

Heavy ion therapy has two definite advantages: good dose localization and higher biological effect. Range calculation of the heavy ions is an important factor in treatment planning. X-ray CT numbers are used to estimate the heavy ion range by looking up values in a conversion table which relates empirically photon attenuation in tissues to particle stopping power; this is one source of uncertainty in the treatment planning. Use of positron emitting radioactive beams along with a positron emission tomograph or a positron camera gives range information and may be used as a means of checking in heavy ion treatment planning. However, the metabolism of the implanted positron emitters in a living object is unpredictable because the chemical forms of these emitters are unknown and the metabolism is dependent on the organ species and may be influenced by many factors such as blood flow rate and fluid components present. In this paper, the washout rate of 11C activity implanted by injecting energetic 11C beams into thigh muscle of a rear leg of a rabbit is presented. The washout was found to consist of two components, the shorter one was about 4.2 +/- 1.1 min and the longer one ranged from 91 to 124 min. About one third of the implanted beta+ activity can be used for imaging and the rest was washed out of the target area.

The application of PET to quality assurance of heavy-ion tumor therapy.

At the new heavy ion tumor therapy facility of the Gesellschaft für Schwerionenforschung at Darmstadt positron emission tomography (PET) has been implemented for in-beam and in-situ therapy control, i.e. during the tumor irradiation. The components necessary for this dedicated PET-imaging and their integration into the framework of therapy planning and quality assurance of heavy ion cancer treatments are presented. Results of the first application of this PET-method to patient treatments are reported.

The investigation of different cameras for in-beam PET imaging.

In situ and in vivo treatment plan verification and beam monitoring as well as dose control during heavy-ion tumour therapy can be performed in principle by measurements of range distributions of beta(+)-emitting nuclei by means of PET techniques. For this purpose the performance of different types of positron camera as well as the results of in-beam PET experiments using beams of beta(+)-active heavy ions (15O, 17F and 19Ne with energies of 300-500 A MeV) are presented. Following the deduced performance requirements a PET scanner that is designed for clinical use in experimental heavy-ion therapy at GSI Darmstadt has been built. This limited angle tomograph consists of two large-area detector heads based on position sensitive BGO detectors and is predicted to perform the measurement of the end point of a beta(+)-emitting ion beam for the verification of a treatment plan with a precision better than 1 mm. The maximum dose applied in the patient thereby is of the magnitude of 10 mGy.