Peak Dose Rate Research Articles

Bringing FLASH to the Clinic: Treatment Planning Considerations for Ultrahigh Dose-Rate Proton Beams

Preclinical research into ultrahigh dose rate (eg, ≥40 Gy/s) "FLASH"-radiation therapy suggests a decrease in side effects compared with conventional irradiation while maintaining tumor control. When FLASH is delivered using a scanning proton beam, tissue becomes subject to a spatially dependent range of dose rates. This study systematically investigates dose rate distributions and delivery times for proton FLASH plans using stereotactic lung irradiation as the paradigm. Stereotactic lung radiation therapy FLASH-plans, using 244 MeV scanning proton transmission beams, with the Bragg peak behind the body, were made for 7 patients. Evaluated parameters were dose rate distribution within a beam, overall irradiation time, number of times tissue is irradiated, and quality of the FLASH-plans compared with the clinical volumetric-modulated arc therapy (VMAT) plans. Sparing of lungs, thoracic wall, and heart in the FLASH-plans was equal to or better than that in the VMAT-plans. For a spot peak dose rate (SPDR, the dose rate in the middle of the spot) of 100 Gy/s, ∼40% of dose is delivered at FLASH dose rates, and for SPDR = 360 Gy/s this increased to ∼75%. One-hundred percent FLASH dose rate cannot be achieved owing to small contributions from distant spots with lower dose rates. The total irradiation time varied between 300 to 730 ms, and around 85% of the dose-receiving body volume was irradiated by either 1 or 2 beams. Clinical implementation of FLASH using scanning proton beams requires multiple treatment planning considerations: dosimetric, temporal, and spatial parameters all seem important. The FLASH efficiency of a scanning proton beam increases with SPDR. The methodology proposed in this proof-of-principle study provides a framework for evaluating the FLASH characteristics of scanning proton beam plans and can be adapted as FLASH parameters are better defined. It currently seems logical to optimize plans for the shortest delivery time, maximum amount of high dose rate coverage, and maximum amount of single beam and continuous irradiation.

Time-resolved dosimetry of pulsed electron beams in very high dose-rate, FLASH irradiation for radiotherapy preclinical studies

Abstract Most anticancer radiation therapy facilities are based on linear electron accelerators with electron–photon conversion providing dose-rates in the range 0.03-0.40 Gy.s−1, and treatment plans usually involve daily fractions of 2 Gy cumulated for up to reaching a total dose close to the limit of tolerance of the normal tissues that surround tumors. We recently developed another methodology named “FLASH” that relies on very high dose-rate facilities and consists in delivering ≥ 10 Gy in a single microsecond pulse of relativistic electrons, or else in a limited number of pulses of 1-2 Gy each given in ≤ 100 ms temporal sequence. In mice FLASH was found to elicit a dramatic decrease of damage to normal tissues whilst keeping the anti-tumor efficiency unchanged. In the following we describe the methods used for beam monitoring in the FLASH mode with emphasis on techniques that provide proportional, time-resolved dosimetry of radiation at the submicrosecond time scale. These methods include measurement of the electron fluence, optically monitored chemical dosimeters in water, solid scintillation and Cerenkov light emission. An application to the calibration of Gafchromic™ films is described and the minimal requirements for dose monitoring in preclinical assays are discussed. Good repeatability and linearity of these techniques in a range of peak dose-rates from 2x102 to 4x107 Gy.s−1 and from 1 mGy to over 30 Gy per microsecond pulse have been obtained with an overall precision better than ± 2%.

Fast dose fractionation using ultra-short laser accelerated proton pulses can increase cancer cell mortality, which relies on functional PARP1 protein

Radiotherapy is a cornerstone of cancer management. The improvement of spatial dose distribution in the tumor volume by minimizing the dose deposited in the healthy tissues have been a major concern during the last decades. Temporal aspects of dose deposition are yet to be investigated. Laser-plasma-based particle accelerators are able to emit pulsed-proton beams at extremely high peak dose rates (~109 Gy/s) during several nanoseconds. The impact of such dose rates on resistant glioblastoma cell lines, SF763 and U87-MG, was compared to conventionally accelerated protons and X-rays. No difference was observed in DNA double-strand breaks generation and cells killing. The variation of the repetition rate of the proton bunches produced an oscillation of the radio-induced cell susceptibility in human colon carcinoma HCT116 cells, which appeared to be related to the presence of the PARP1 protein and an efficient parylation process. Interestingly, when laser-driven proton bunches were applied at 0.5 Hz, survival of the radioresistant HCT116 p53−/− cells equaled that of its radiosensitive counterpart, HCT116 WT, which was also similar to cells treated with the PARP1 inhibitor Olaparib. Altogether, these results suggest that the application modality of ultrashort bunches of particles could provide a great therapeutic potential in radiotherapy.

Investigation of Dose Rates Exterior to an Above-Ground Waste Storage Facility Using Radiation Transport Models

The dose rate profile at different heights above the ground and as a function of distance from the north, west, and south walls of an above-ground waste storage facility was analyzed using the Monte Carlo n-Particle Transport eXtended (MCNPX) radiation transport code. The waste storage facility houses 9,996 waste barrels of conditioned waste. The facility has concrete shielding added to the building walls on the north, west, and east sides, with no such additional shielding towards the roof or the south side wall; instead, the distance from the first row of barrels to the wall is extended to allow for maneuverability of a crane on the south side. The dose rate is computed as a function of distance using MCNPX and assuming a homogeneous Co distribution in each waste barrel. Different dose regions are identified and analyzed based on graphical features and best-fit functions. The dose rates were expected to be largest at the wall of the facility and subsequently decrease continuously with distance from the repository; however, our analysis indicates a peak in dose rate observed for all heights on the north and west sides of the facility. This peak is likely due to scattering in the shielding material and atmosphere, and possibly could be ascribed to skyshine. The difference between the dose rate at 1 m outside the wall and the peak dose rate is significant, and indicates that the dose rate measured close to the wall may not always be conservative for extended sources, such as an above-ground waste storage facility.

Monte Carlo optimization of a microbeam collimator design for use on the small animal radiation research platform (SARRP)

Microbeam radiation therapy (MRT) is a pre-clinical, spatially-fractionated treatment modality noted for its ability to achieve a large differential response between normal and tumoral tissues. In the present study, TOPAS Monte Carlo (MC) simulations were used to optimize the design of a compact, affordable multi-slit collimator (MSC) suitable for use with the small animal radiation research platform (SARRP). MRT dose distributions in a (1 × 1 × 3)cm3 water phantom were simulated for a tungsten MSC using different focal spot sizes (0.4, 3 mm), beam energies (40, 80, 220 kVp), slit widths (100, 125, 150, 175, 200 µm), collimator thicknesses (1.5, 2.5, 3 cm) and collimator-to-surface distances (CSD of 1 and 3 cm). Key MRT figures of merit, namely the peak-to-valley dose ratio (PVDR), full-width at half-maximum and peak dose rate were determined. Use of the small focal spot maximized the PVDR (~40 at surface) and reduced the system’s sensitivity to changes in CSD, but decreased the collimated beam output to 55.2 cGy min−1. The large focal spot was ill-suited for large CSD irradiations, but increased the beam output by a factor of 2.8, to 153.0 cGy min−1, and decreased the sensitivity to changes in slit width. A modular MSC, using divergent plastic spacer materials in place of excavated slits, was also investigated. Polypropylene and polyethylene terephthalate material spacers were considered and while neither reduced the PVDR compared to air slits, the dose rate was reduced by 37% and 47%, respectively. Lastly, a steel parallel-slit MSC was used in a preliminary test of MRT delivery using the SARRP. Discrepancies between the results of film dosimetry and the corresponding MC simulations highlight the need to fabricate a more well-defined collimator for use in future validation and radiobiological work. The simulated results of this study are being used to inform the design of such a collimator, which will additionally boast a high degree of modularity at reasonable cost.

Radial wire-array rod-pinch diodes

This paper presents the results of experiments on the low-impedance diode formation in the configuration of a rodpinch diode shorted with a radial wire array. It has been found that using an axially asymmetric configuration with a radial wire array instead of an axisymmetric configuration with a radial foil does not substantially modify the focusing of the electron beam on the tip of the rod. Radial wire rod-pinches driven by the MIG generator (1 MV, 2 MA, 80 ns) produce 10-ns long X-ray pulses with the peak dose rate up to 1.1×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">8</sup> rad/s and the total dose per pulse up to 2 rad. 0.8-mm size point-like X-ray sources attractive for off-axis radiography were observed.

1568P - Development of laser-driven proton beam therapy

ABSTRACT Aim: Proton beams by their advantageous dose profile over conventional photon and electron beams may provide higher dose conformity and better healthy tissue sparing. But due to high costs and huge size of existing facilities, proton therapy is limited to few centers. A novel proton acceleration, on µm scale by ultra-intense lasers, promises compact accelerators and beam delivery systems. Unlike conventional proton beams, laser-accelerated proton (LAP) beam is characterized by short ultra-intense pulses with peak dose rates exceeding conventional values by ∼9 orders of magnitude but low repetition rate, broad energy spread and large divergence. They require completely new techniques of beam transport, dose delivery and quality assurance along with radiobiological characterization. Methods: The presented work is an ongoing joint translational research project of several institutions in Germany aiming to establish LAP therapy. In parallel to the development of high power laser systems and laser targets to generate stable and reproducible LAP beams, a dedicated radiation oncology focused research program is being followed. Results: Laser-based technology was established for cell and small animal irradiation. The high power laser system DRACO was setup and optimized for long-term stable proton acceleration. A dedicated fixed-beam transport system with integrated energy selection and field shaping as well as real time dose monitoring was established. The suitability and reliability of all components was proven in systematic radiobiological studies over months. No overall difference in the biological effectiveness between laser-accelerated and conventional beams was detected to date. For translation towards patient irradiation, increase of proton energy from ∼25 to ∼230 MeV by increasing the laser power from ∼100 TW to ∼1 PW is required and the development of PW laser is in progress. Furthermore, a compact 360° isocentric proton gantry was designed, based on novel light-weight high-field pulsed magnets. This gantry is ∼2.5x smaller than conventional proton gantries. The necessary pulsed magnets are being developed together with novel dose delivery strategy for LAP. Conclusions: LAP therapy is a promising alternative, yet require substantial development with a clinical prototype in some years. Supported by German BMBF, no. 03Z1N511. Disclosure: All authors have declared no conflicts of interest.

The impact of cell proliferation and radionuclide uptake rate in radio-immunotherapy

Purpose The instantaneous-uptake model of O’Donoghue [”The impact of tumor cell proliferation in radio-immunotherapy”, Cancer 73, 974–980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is being extended to arbitrary uptake rates of the radiopharmaceutical in tumor cells. Methods The time derivative of the survival curve is examined and an expression for the minimum of the surviving fraction is deduced along with a new expression for the biological effective dose (BED). Surviving fractions are calculated over a clinically relevant parameter range to establish general trends. Results Results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1–24 h, extrapolated initial dose-rates 0.5–1 Gy h-1 and a biological clearance half-life of 7 days. Cell doubling time equals 2 days. The exponential-uptake rate of the radiopharmaceutical by the targeted cells appears to have a considerable effect on the survival of a proliferating cell population (even for uptake half-times of only a few hours) and thence might need to be considered in the radiobiological models of tumor cell-kill in radio-immunotherapy. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for radionuclides with higher half-life. Moreover, the sensitivity of the cell survival on the uptake was found to be higher for the tumor cells with higher radio-sensitivity. Conclusion Neglecting an uptake phase may result in a considerable overestimation of cell kill.

Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells

Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10(10)Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone.

Technical Note: Impact of cell repopulation and radionuclide uptake phase on cell survival.

To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. The instantaneous-uptake model of O'Donoghue ["The impact of tumor cell proliferation in radioimmunotherapy," Cancer 73, 974-980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). Surviving fractions are calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1-24 h, extrapolated initial dose-rates 0.5-1 Gy h(-1), and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy(-1). It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient. The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.

WE‐EF‐BRA‐09: Microbeam Radiation Therapy Enhances Tumor Drug Uptake of PEGylated Liposomal Doxorubicin (PLD) in a Triple Negative Breast Cancer GEM Model

Purpose:Overcoming low anti‐cancer drug uptake in tumors is a key challenge limiting its clinical use. We propose to enhance the drug delivery using upfront Microbeam Radiation Therapy (MRT). MRT is a preclinical cancer therapy that utilizes microplanar beams to deliver spatially oscillating planes of high and low doses. Animal studies have demonstrated that ultrahigh dose (100s Gy) MRT eradicates tumors without damaging the function of normal tissue exposed to the same radiation. Our previous study indicated that MRT induces intense angiogenesis in tumor rim and surrounding normal tissue 1–2 days post radiation. We hypothesize that the tumor microenvironment modulation induced by MRT may enhance carrier‐mediated agent drug delivery to tumors with inherent poor drug uptake. We thus investigated MRT‐induced pharmacokinetics (PK) of PEGylated liposomal doxorubicin (PLD), a nano‐scale doxorubicin, in T11 genetically engineered mouse model of triple negative breast cancer.Methods:A research irradiator (160kVp, RadSource Technologies) with a customized collimator was used to produce the MRT microbeam of in average 390µm width and 1190µm peak‐to‐peak distance. The peak dose rate of 1–2Gy/min. Dosimetry is by EBT3 film cross‐calibrated with ion chamber at large fields. All mice were administered PLD at 6mg/kg IV x1 at 16h post MRT and sacrificed at 5min, 6h, 24h, and 96h post PLD administration (n=3 or 4 per group).Results:The MRT(28Gy)+PLD group mice had a total doxorubicin tumor concentration (area‐under‐the concentration‐curve, AUC) of 206,040ng/mL•h, 3.71 times the concentration of the PLD‐alone group. The MRT(34Gy)+PLD group had a higher mean total doxorubicin concentration in tumor (20,779ng/ml) than the MRT(28Gy)+PLD group (10,665ng/ml).Conclusion:Our preliminary results indicate that microbeam radiation therapy (MRT) can enhance nano‐scale anti‐cancer drug delivery to tumors approximately 4‐fold. The exact working mechanism, the comparison with broad beam irradiation, and optimization of MRT for drug delivery enhancement are under investigation.

A Real-Time Skin Dose Tracking System for Biplane Neuro-Interventional Procedures.

A biplane dose-tracking system (Biplane-DTS) that provides a real-time display of the skin-dose distribution on a 3D-patient graphic during neuro-interventional fluoroscopic procedures was developed. Biplane-DTS calculates patient skin dose using geometry and exposure information for the two gantries of the imaging system acquired from the digital system bus. The dose is calculated for individual points on the patient graphic surface for each exposure pulse and cumulative dose for both x-ray tubes is displayed as color maps on a split screen showing frontal and lateral projections of a 3D-humanoid graphic. Overall peak skin dose (PSD), FOV-PSD and current dose rates for the two gantries are also displayed. Biplane-DTS uses calibration files of mR/mAs for the frontal and lateral tubes measured with and without the table in the beam at the entrance surface of a 20 cm thick PMMA phantom placed 15 cm tube-side of the isocenter. For neuro-imaging, conversion factors are applied as a function of entrance field area to scale the calculated dose to that measured with a Phantom Laboratory head phantom which contains a human skull to account for differences in backscatter between PMMA and the human head. The software incorporates inverse-square correction to each point on the skin and corrects for angulation of the beam through the table. Dose calculated by Biplane DTS and values measured by a 6-cc ionization chamber placed on the head phantom at multiple points agree within a range of -3% to +7% with a standard deviation for all points of less than 3%.

Radiation dosimetry and biodistribution of the translocator protein radiotracer [11C]DAA1106 determined with PET/CT in healthy human volunteers

IntroductionWhen microglia become activated (an integral part of neuroinflammation), cellular morphology changes and expression of translocator protein (TSPO) 18kDa is increased. Over the past several years, [11C]DAA1106 has emerged as a reliable radiotracer for labeling TSPO with high affinity during positron emission tomography (PET) scanning. While [11C]DAA1106 PET scanning has been used in several research studies, a radiation dosimetry study of this radiotracer in humans has not yet been published. MethodsTwelve healthy participants underwent full body dynamic [11C]DAA1106 PET scanning, with 8 sequential whole body scans (approximately 12 bed positions each), following a single injection. Regions of interest were drawn manually, and time activity curves (TACs) were obtained for 15 organs. OLINDA/EXM 1.1 was used to compute radiation absorbed doses to the target organs, as well as effective dose (ED) and effective dose equivalent (EDE). ResultsThe ED and EDE were 4.06 ± 0.58μSv/MBq and 5.89 ± 0.83μSv/MBq, respectively. The highest absorbed doses were to the heart wall, kidney, liver, pancreas, and spleen. TACs revealed that peak dose rates are during the first scan (at 6min) for all organs other than the urinary bladder wall, which had its peak dose rate during the fourth scan (at 30min). ConclusionsThe recently developed radiotracer [11C]DAA1106 has its EDE and target-organ absorbed dose such that, for a single administration, its radiation dosimetry is well within the U.S. FDA guidelines for basic research studies in adults. This dose level implies that the dosimetry for multiple [11C]DAA1106 scans within a given year also falls within FDA guidelines, and this favorable property makes this radiotracer suitable for examining microglial activation repeatedly over time, which may in the future be useful for longitudinal tracking of disease progression and monitoring of therapy response in conditions marked by neuroinflammation (e.g., head trauma and multiple sclerosis).

South Pole neutron monitor forecasting of solar proton radiation intensity

[1] We describe a practical system for forecasting peak intensity and fluence of solar energetic protons in the tens to hundreds of MeV energy range. The system could be useful for forecasting radiation hazard, because peak intensity and fluence are closely related to the medical physics quantities peak dose rate and total dose. The method uses a pair of ground-based detectors located at the South Pole to make a measurement of the solar particle energy spectrum at relativistic (GeV) energies, and it then extrapolates this spectrum downward in energy to make a prediction of the peak intensity and fluence at lower energies. A validation study based upon 12 large solar particle events compared the prediction with measurements made aboard GOES spacecraft. This study shows that useful predictions (logarithmic correlation greater than 50%) can be made down to energies of 40–80 MeV (GOES channel P5) in the case of peak intensity, with the prediction leading the observation by 166 min on average. For higher energy GOES channels, the lead times are shorter, but the correlation coefficients are larger.

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

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. 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. 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. TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

Radiobiological Effectiveness of Laser Accelerated Electrons in Comparison to Electron Beams from a Conventional Linear Accelerator

The notable progress in laser particle acceleration technology promises potential medical application in cancer therapy through compact and cost effective laser devices that are suitable for already existing clinics. Previously, consequences on the radiobiological response by laser driven particle beams characterised by an ultra high peak dose rate have to be investigated. Therefore, tumour and non-malignant cells were irradiated with pulsed laser accelerated electrons at the JETI facility for the comparison with continuous electrons of a conventional therapy LINAC. Dose response curves were measured for the biological endpoints clonogenic survival and residual DNA double strand breaks. The overall results show no significant differences in radiobiological response for in vitro cell experiments between laser accelerated pulsed and clinical used electron beams. These first systematic in vitro cell response studies with precise dosimetry to laser driven electron beams represent a first step toward the long term aim of the application of laser accelerated particles in radiotherapy.

Modeling the 2003 Halloween events with EMMREM: Energetic particles, radial gradients, and coupling to MHD

present a study of the October/November 2003 Halloween solar energetic particle events with an energetic particle acceleration and propagation model that is part of EMMREM, highlighting the current ability of the framework to make predictions at various locations of the inner heliosphere. We compare model predictions with Ulysses observations of protons at energies above 10 MeV in order to obtain realistic proton fluxes and calculate radial gradients for peak fluxes, event fluences, and radiation dosimetric quantities. From our study, we find that a power law with an index of −3.55 at energy of 200 MeV describes the time‐integrated energetic proton fluence dependence on radial distances beyond 1 AU for the 2003 Halloween events, and an index of −4.18 is appropriate for peak proton fluxes at that energy. Calculations of radiation doses based on these simulations show average power law indices of −4.32 and −3.64 for peak dose rates and accumulated doses, respectively. In an effort to improve the predictions, we have coupled our kinetic code to results from a 3‐D heliospheric magnetohydrodynamic model, WSA/Enlil. While predictions with the coupled model overall show worse agreement than simulations with steady state solar wind conditions for these large events, the capability to couple energetic particle propagation and numerical models of the solar wind is an important step in the future development of space weather modeling.

A new neutron monitor with silver activation

Abstract A moderator-type neutron monitor has been developed, which registers delayed beta rays from neutron-induced silver activation and which is able to measure dose equivalent in pulsed fields with peak dose rates of several thousand Sv h−1. The monitor uses four silicon diodes in the centre of a polyethylene moderator, 30 cm in diameter. Two of the diodes are covered by natural silver foils and two of them by tin foils. The latter are used to subtract photon-induced pulses. For registering signals, a pulse height threshold is set at 662 keV, which minimizes the effect of 137Cs and lower energy radiation and – in addition – enhances the detection of beta rays from the shorter half-life silver isotope 110Ag (25 s) as compared to the longer half-life isotope 108Ag (144 s). The results of measurements in neutron and photon calibration fields, of MCNPX neutron response calculations and of first measurements in a high-intensity pulsed field at the PSI accelerator are shown.

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

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. 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. 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. 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.

Spectromicroscopic film dosimetry for high-energy microbeam from synchrotron radiation

A microscope with band-pass filters was used to measure the optical-density distribution of GafChromic films irradiated with multi-slit microbeam X-rays. The planar width was 25 μm, and the center-to-center distance was 200 μm. The peak and valley dose rates in air were found to be 120 and 0.7 Gy/s, respectively. In a polymethylmethacrylate phantom, the peak-to-valley dose ratio decreased to 80 at a 1-mm depth. Doses calculated with the PENELOPE code agreed with those around the peak but became smaller in the valley.