Plane-parallel Ionization Chambers Research Articles

Monitoring and Control of Irradiation with Carbon Ions During Radiobiological Experiments at the RBS Experimental Set-Up

The RBS experimental set-up has been working in every accelerator session of the U-70 accelerator complex since 2015. The main users of the set-up are radiobiologists and physicians. The direction of research is radiobiological experiments with extracted beams of accelerated carbon ions and preclinical studies aimed at the development of domestic methods of ion therapy. The requirements for irradiation of samples with carbon ions are very high: irradiation uniformity is no worse than 95%, positioning accuracy is no worse than 0.1 mm, dose delivery accuracy is no worse than ±2.5%. The article describes the instruments and devices that are used to support radiobiological experiments at the RBS installation: a plane-parallel ionization chamber, a mosaic ionization chamber, a water phantom with a 3D movement system, a 6-axis table, a degrader, a laser positioning system, clinical dosimeters. Programs for working with this equipment and archiving the data obtained are described.

An SSDLs calibration method for the kerma-area product meter

The kerma-area product meter (KAP meter) is mainly used for quality assurance in medical imaging research, providing dose quality assessment or dose monitoring for patients. It can be calibrated either in the laboratory or on-site. The purpose of this study is to propose a method for calibrating the KAP meter using a plane-parallel transmission ionization chamber in the SSDLs. In the range of 50 kV–150 kV, under RQR (standard radiation qualities) and RQR additional filtering conditions of the KAP meter, the correction factor NQm of the transmission ionization chamber is calculated to select two types of KAP meters for the calibration of the transmitted beam. The collimators used to limit the size of the radiation field are respectively 50.07 mm in length, 30.03 mm in length, and 20.05 mm in radius. This method, with uncertainty not exceeding 3.0% while improving calibration efficiency, can replace the unit-specific correction of the laboratory method (Toroi et al., 2008).

2942: Impact of the effective point of measurement for plane-parallel ionization chambers in proton beams

2942: Impact of the effective point of measurement for plane-parallel ionization chambers in proton beams

Monte Carlo simulation of initial and volume ion recombination correction factor in plane parallel ionization chambers exposed to ion beams

Objective. Accurate reference dosimetry with ionization chambers (ICs) relies on correcting for various influencing factors, including ion recombination. Theoretical frameworks, such as the Boag and Jaffe theories, are conventionally used to describe the ion recombination correction factors. Experimental methods are time consuming, the applicability may be limited and, in some cases, impractical to be used in clinical routine. The development of simulation tools becomes necessary to enhance the understanding of recombination under circumstances that may differ from conventional use. Before progressing, it is crucial to benchmark novel approaches to calculate ion recombination losses under known conditions. In this study, we introduce and validate a versatile simulation tool based on a Monte Carlo scheme for calculating initial and volume ion recombination correction factors in air-filled ICs exposed to ion beams with clinical dose rates. Approach. The simulation includes gaussian distribution of ion positions to model the distribution of charge carriers along the chamber volume. It accounts for various physical transport effects, including drift, diffusion, space charge screening and free electron fraction. To compute ion recombination, a Monte Carlo scheme is used due to its versatility in multiple geometries, without exhibiting convergence problems associated with numerically solved procedures. Main results. The code is validated in conventional dose rates against Jaffe’s theory for initial recombination and Boag’s theory for volume recombination based on parameters derived from experimental data including proton, helium and carbon ion beams measured with a plane parallel IC. Significance. The simulation demonstrates excellent agreement, typically 0.05% or less relative difference with the theoretical and experimental data. The current code successfully predicts ion recombination correction factors, in a large variety of ion beams, including different temporal beam structures.

Collection efficiencies of cylindrical and plane parallel ionization chambers: analytical and numerical results and implications for experimentally determined correction factors

Objectives. To derive a collection efficiency formula, fGauss , for cylindrical ionization chambers in pulsed radiation beams from a volume recombination model of Boag et al (1996 Phys. Med. Biol. 41 885–97) including free electrons. To validate fGauss and a parallel plate chamber formula fexp using an ion transport code and calculate changes in collection efficiencies caused by electric field charge screening at 0.1–100 mGy doses-per-pulse. And to determine collection efficiencies CE∞ predicted at infinite voltage in the absence of avalanche effects by fitting scaled formulae to efficiencies computed for 100–400 V chamber voltages and 10 and 100 mGy doses-per-pulse. Approach. Calculations were performed for an idealized parallel plate chamber with 2 mm electrode separation d , and for an idealized cylindrical chamber with 0.5 and 2.333 mm inner and electrode radii rin and rout . Main results. fGauss and fexp predict the same collection efficiencies for cylindrical and parallel plate chambers satisfying d2=(rout2−rin2)ln(rout/rin)/2 , an equivalence condition met by the chambers studied. Without charge screening, efficiencies computed using the code equalled fGauss and fexp . With screening, efficiencies changed by ⩽0.03%, ⩽1.1% and ⩽21.3% at 1, 10 and 100 mGy doses-per-pulse, and differed between the chambers by ⩽0.9% and ⩽19.6% at ⩽10 and 100 mGy dose-per-pulse. For fits of fexp and fGauss , CE∞ values were ⩽1.2% and ⩽17.6% from unity at 10 and 100 mGy per pulse respectively, closer than for other formulae tested. Significance. Allowing for screening, fGauss and fexp described computed collection efficiencies to within 0.03%, 1.1% and 21.3% at doses-per-pulse ⩽1, 10 and 100 mGy. Equivalence of the two chambers broke down at 100 mGy per pulse. Departures of CE∞ values from unity suggest that collection efficiencies determined experimentally by fitting fGauss or fexp to readings made at multiple voltages will be accurate to within 1.2% and 17.6% at 10 and 100 mGy per pulse respectively.

Characterization of a commercial plastic scintillator for electron FLASH dosimetry.

This study investigated the potential of a commercially available plastic scintillator, the Exradin W2, as a real-time dosimeter for ultra-high-dose-rate (UHDR) electron beams. This work aimed to characterize this system's performance under UHDR conditions and addressed limitations inherent to other conventional dosimetry systems. We assessed the W2's performance as a UHDR electron dosimeter using a 16 MeV UHDR electron beam from the FLASH research extension (FLEX) system. Additionally, the vendor provided a beta firmware upgrade to better handle the processing of the high signal generated in the UHDR environment. We evaluated the W2 regarding dose-per-pulse, pulse repetition rate, charge versus distance, and pulse linearity. Absorbed dose measurements were compared against those from a plane-parallel ionization chamber, optically stimulated luminescent dosimeters and radiochromic film. We observed that the 1×1mm W2 scintillator with the MAX SD was more suitable for UHDR dosimetry compared to the 1×3mm W2 scintillator, capable of matching film measurements within 2% accuracy for dose-per-pulse up to 3.6Gy/pulse. The W2 accurately ascertained the inverse square relationship regarding charge versus virtual source distance with R2 of ∼1.00 for all channels. Pulse linearity was accurately measured with the W2, demonstrating a proportional response to the delivered pulse number. There was no discernible impact on the measured charge of the W2 when switching between the available repetition rates of the FLEX system (18-180pulses/s), solidifying consistent beam output across pulse frequencies. This study tested a commercial plastic scintillator detector in a UHDR electron beam, paving the way for its potential use as a real-time, patient-specific dosimetry tool for future FLASH radiotherapy treatments. Further research is warranted to test and improve the signal processing of the W2 dosimetry system to accurately measure in UHDR environments using exceedingly high dose-per-pulse and pulse numbers.

Development and characterization of a dedicated dose monitor for ultrahigh-dose-rate scanned carbon-ion beams

The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DRspot)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8–12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DRspot). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.

Experimental comparison of cylindrical and plane parallel ionization chambers for reference dosimetry in continuous and pulsed scanned proton beams

Objective. In this experimental work we compared the determination of absorbed dose to water using four ionization chambers (ICs), a PTW-34045 Advanced Markus, a PTW-34001 Roos, an IBA-PPC05 and a PTW-30012 Farmer, irradiated under the same conditions in one continuous- and in two pulsed-scanned proton beams. Approach. The ICs were positioned at 2 cm depth in a water phantom in four square-field single-energy scanned-proton beams with nominal energies between 80 and 220 MeV and in the middle of 10 × 10 × 10 cm3 dose cubes centered at 10 cm or 12.5 cm depth in water. The water-equivalent thickness (WET) of the entrance window and the effective point of measurement was considered when positioning the plane parallel (PP) ICs and the cylindrical ICs, respectively. To reduce uncertainties, all ICs were calibrated at the same primary standards laboratory. We used the beam quality (k Q ) correction factors for the ICs under investigation from IAEA TRS-398, the newly calculated Monte Carlo (MC) values and the anticipated IAEA TRS-398 updated recommendations. Main results. Dose differences among the four ICs ranged between 1.5% and 3.7% using both the TRS-398 and the newly recommended k Q values. The spread among the chambers is reduced with the newly k Q values. The largest differences were observed between the rest of the ICs and the IBA-PPC05 IC, obtaining lower dose with the IBA-PPC05. Significance. We provide experimental data comparing different types of chambers in different proton beam qualities. The observed dose differences between the ICs appear to be related to inconsistencies in the determination of the k Q values. For PP ICs, MC studies account for the physical thickness of the entrance window rather than the WET. The additional energy loss that the wall material invokes is not negligible for the IBA-PPC05 and might partially explain the low k Q values determined for this IC. To resolve this inconsistency and to benchmark MC values, k Q values measured using calorimetry are needed.

Automated determination of the ion-recombination correction factor (ksat) in ultra-high dose rate electron radiation therapy.

Plane-parallel ionization chambers are the recommended secondary standard systems for clinical reference dosimetry of electrons. Dosimetry in high dose rate and dose-per-pulse (DPP) is challenging as ionization chambers are subject to ion recombination, especially when dose rate and/or DPP is increased beyond the range of conventional radiotherapy. The lack of universally accepted models for correction of ion recombination in UDHR is still an issue as it is, especially in FLASH-RT research, which is crucial in order to be able to accurately measure the dose for a wide range of dose rates and DPPs. The objective of this study was to show the feasibility of developing an Artificial Intelligence model to predict the ion-recombination factor-ksat for a plane-parallel Advanced Markus ionization chamber for conventional and ultra-high dose rate electron beams based on machine parameters. In addition, the predicted ksat of the AI model was compared with the current applied analytical models for this correction factor. A total number of 425 measurements was collected with a balanced variety in machine parameter settings. The specific ksat values were determined by dividing the output of the reference dosimeter (optically stimulated luminescence [OSL]) by the output of the AM chamber. Subsequently, a XGBoost regression model was trained, which used the different machine parameters as input features and the corresponding ksat value as output. The prediction accuracy of this regression model was characterized by R2-coefficient of determination, mean absolute error and root mean squared error. In addition, the model was compared with the Two-Voltage (TVA) method and empirical Petersson model for 19 different dose-per-pulse values ranging from conventional to UDHR regimes. The Akiake Information criterion (AIC) was calculated for the three different models. The XGBoost regression model reached a R2-score of 0.94 on the independent test set with a MAE of 0.067 and RMSE of 0.106. For the additional 19 random data points, the ksat values predicted by the XGBoost model showed to be in agreement, within the uncertainties, with the ones determined by the Petersson model and better than the TVA method for doses per pulse>3.5Gy with a maximum deviation from the ground truth of 14.2%, 16.7%, and -36.0%, respectively, for DPP>4Gy. The proposed method of using AI for ksat determination displays efficiency. For the investigated DPPs, the ksat values obtained with the XGBoost model were in concurrence with the ones obtained with the current available analytical models within the boundaries of uncertainty, certainly for the DPP characterizing UDHR. But the overall performance of the AI model, taking the number of free parameters into account, lacked efficiency. Future research should optimize the determination of the experimental ksat, and investigate the determination the ksat for DPPs higher than the ones investigated in this study, while also evaluating the prediction of the proposed XGBoost model for UDHR machines of different centers.

Beam monitor chamber calibration of a synchro-cyclotron high dose rate per pulse pulsed scanned proton beam

Objective. Ionization chambers, mostly used for beam calibration and for reference dosimetry, can show high recombination effects in pulsed high dose rate proton beams. The aims of this paper are: first, to characterize the linearity response of newly designed asymmetrical beam monitor chambers (ABMC) in a 100–226 MeV pulsed high dose rate per pulse scanned proton beam; and secondly, to calibrate the ABMC with a PPC05 (IBA Dosimetry) plane parallel ionization chamber and compare to calibration with a home-made Faraday cup (FC). Approach. The ABMC response linearity was evaluated with both the FC and a PTW 60019 microDiamond detector. Regarding ionometry-based ABMC calibration, recombination factors were evaluated theoretically, then numerically, and finally experimentally measured in water for a plane parallel ionization chamber PPC05 (IBA Dosimetry) through k s saturation curves. Finally, ABMC calibration was also achieved with FC and compared to the ionometry method for 7 energies. Main results. Linearity measurements showed that recombination losses in the new ABMC design were well taken into account for the whole range of the machine dose rates. The two-voltage-method was not suitable for recombination correction, but Jaffé’s plots analysis was needed, emphasizing the current IAEA TRS-398 reference protocol limitations. Concerning ABMC calibration, FC based absorbed dose estimation and PPC05-based absorbed dose estimation differ by less than 6.3% for the investigated energies. Significance. So far, no update on reference dosimetry protocols is available to estimate the absorbed dose in ionization chambers for clinical high dose rate per pulse pulsed scanned proton beams. This work proposes a validation of the new ABMC design, a method to take into account the recombination effect for ionometry-based ABMC calibration and a comparison with FC dose estimation in this type of proton beams.

Reconfiguring a Plane-Parallel Transmission Ionization Chamber to Extend the Operating Range into the Ultra-High Dose-per-pulse Regime.

This study aims to investigate the feasibility of enhancing the charge collection efficiency (CCE) of a transmission chamber by reconfiguring its design and operation. The goal was to extend the range of dose-per-pulse (DPP) values with no or minimal recombination effects up to the ultra-high dose rate (UHDR) regime. The response of two transmission chambers, with electrode distance of 1 mm and 0.6 mm, respectively, was investigated as a function of applied voltage. The chambers were mounted one-by-one in the electron applicator of a 10 MeV FLASH-modified clinical linear accelerator. The chamber signals were measured as a function of nominal DPP, which was determined at the depth of dose maximum using EBT-XD film in solid water and ranged from 0.6 mGy per pulse to 0.9 Gy per pulse, for both the standard voltage of 320 V and the highest possible safe voltage of 1,200 V. The CCE was calculated and fitted with an empirical logistic function that incorporated the electrode distance and the chamber voltage. The CCE decreased with increased DPP. The CCE at the highest achievable DPP was 24% (36%) at 320 V and 51% (82%) at 1,200 V, for chambers with 1 mm (0.6 mm) electrode distance. For the combination of 1,200 V- and 0.6-mm electrode distance, the CCE was ∼100% for average dose rate up to 70 Gy/s at the depth of dose maximum in the phantom at a source-to-surface distance of 100 cm. Our findings indicate that minor modifications to a plane-parallel transmission chamber can substantially enhance the CCE and extending the chamber's operating range to the UHDR regime. This supports the potential of using transmission chamber-based monitoring solutions for UHDR beams, which could facilitate the delivery of UHDR treatments using an approach similar to conventional clinical delivery.

Electron Beams Commissioning and Initial Measurements on an Elekta Synergy Platform Linear Accelerator

A linear accelerator (Linac) must be commissioned for use in treating cancer patients. This research work aims to analyze part of the electron beam data produced by the Elekta Synergy Platform Linac at the radiotherapy department at Tripoli University Hospital, Tripoli, Libya. In this paper, percentage depth dose (PDD), beam profile and applicators factor were studied at five different electron beam energies (4, 6, 8, 10 and 12 MeV). The relative measurement part of this study was carried out using a PTW MP3-M 3D water scanning system, and the absolute measurement was taken using a plane parallel ionization chamber and a unidose E electrometer. The analysis for these measurements has yielded the following results: a) The Penetrative qualities of all the electron beam energies were within the manufacturer's tolerance limits of ±1%; b) the maximum values of beam flatness of 2.94 and beam symmetry of 1.93 are within the accepted limits of International Electrotechnical Commission criteria; c) A penumbra maximum value of 1.30 was measured at the 4-MeV electron beam energy and using a 14×14 cm2 applicator size. All the obtained parameters were within the permissible limits. Therefore, the electron beams can be safely used for clinical purposes.

Technical note: Determination of proton linear energy transfer from the integral depth dose.

Proton linear energy transfer (LET) is associated with the relative biological effectiveness of radiation on tissues. Monte Carlo (MC) simulations have been known to be the preferred method to calculate LET. Detectors have also been built to measure LET, but they need to be calibrated with MC simulations. To propose and test a MC-free method for determining LET from the measured integral depth dose (LFI) of the protons of interest. LFI consists of three steps: (1) IDD measurements, (2) extraction of energy spectrum (ES) from the IDD, and (3) LET determination from the extracted ES and the stopping power of each energy. To validate the accuracy of the extraction of ES, we use Gaussian ES to synthesize IDD, extract ES from the synthesized IDD, and then compare the original (ground truth) and extracted ES. LETs calculated from the original and extracted ES are also compared. To obtain the LET of protons of interest, we measure IDDs by a large-area plane-parallel ionization chamber in water. Finally, TOPAS MC is employed to simulate IDDs, ES, and LETs. From the simulated IDD, the extracted ES and LET are compared with the simulations from TOPAS MC. From the synthesized IDDs, the LETs agreed excellently when the peak energies ≥10 and 1.25 MeV with depth resolutions 0.1and 0.01mm, respectively. For energy<1.25 MeV, even higher depth resolution than 0.01mm is required. From the MC simulated IDDs, our track-averaged LET excellently agreed with MC simulation, but not the LETd. Our LETd was smaller than MC simulated LETd in the shallow region but larger in the distal Bragg peak region. LET can be accurately determined from the IDD. This method can be used in the clinic to commission or validate LETs from other measurement methods or a treatment planning system.

Monte Carlo calculated beam quality correction factors for high energy electron beams

Purpose:As the dosimetry protocol TRS 398 is being revised and the ICRU report 90 provides new recommendations for density correction as well as the mean ionization energies of water and graphite, updated beam quality correction factors kQ are calculated for reference dosimetry in electron beams and for independent validation of previously determined values. Methods:Monte Carlo simulations have been performed using EGSnrc to calculate the absorbed dose to water and the dose to the active volumes of ionization chambers SNC600c, SNC125c and SNC350p (all Sun Nuclear, A Mirion Medical Company, Melbourne, FL). Realistic clinical electron beam spectra were used to cover the entire energy range of therapeutic electron accelerators. The Monte Carlo simulations were validated by measurements on a clinical linear accelerator.With regards to the cylindrical chambers, the simulations were performed according to the setup recommendations of TRS 398 and AAPM TG 51, i.e. with and without consideration of a reference point shift by rcav/2. Results:kQ values as a function of the respective beam quality specifier R50 were fitted by recommended equations for electron beam dosimetry in the range of 5 MeV to 18 MeV. The fitting curves to the calculated values showed a root mean square deviation between 0.0016 and 0.0024. Conclusion:Electron beam quality correction factors kQ were calculated by Monte Carlo simulations for the cylindrical ionization chambers SNC600c and SNC125c as well as the plane parallel ionization chamber SNC350p to provide updated data for the TRS 398 and TG 51 dosimetry protocols.

Proton dosimetry in a magnetic field: Measurement and calculation of magnetic field correction factors for a plane-parallel ionization chamber.

The combination of magnetic resonance imaging and proton therapy offers the potential to improve cancer treatment. The magnetic field (MF)-dependent change in the dosage of ionization chambers in magnetic resonance imaging-integrated proton therapy (MRiPT) is considered by the correction factor , which needs to be determined experimentally or computed via Monte Carlo (MC)simulations. In this study, was both measured and simulated with high accuracy for a plane-parallel ionization chamber at different clinical relevant proton energies and MFstrengths. The dose-response of the Advanced Markus chamber (TM34045, PTW, Freiburg, Germany) irradiated with homogeneous 10 10 cm quasi mono-energetic fields, using 103.3, 128.4, 153.1, 223.1, and 252.7 MeV proton beams was measured in a water phantom placed in the MF of an electromagnet with MF strengths of 0.32, 0.5, and 1 T. The detector was positioned at a depth of 2 g/cm in water, with chamber electrodes parallel to the MF lines and perpendicular to the proton beam incidence direction. The measurements were compared with TOPAS MC simulations utilizing COMSOL-calculated 0.32, 0.5, and 1 T MF maps of the electromagnet. was calculated for the measurements for all energies and MF strengths based on the equation: , where and were the temperature and air-pressure corrected detector readings with and without the MF, respectively. MC-based correction factors were determined as , where and were the doses deposited in the air cavity of the ionization chamber model with and without the MF, respectively. Furthermore, MF effects on the chamber dosimetry are studied using MC simulations, examining the impact on the absorbed dose-to-water ( ) and the shift in depth of the Braggpeak. The detector showed a reduced dose-response for all measured energies and MF strengths, resulting in experimentally determined values larger than unity. For all energies and MF strengths examined, ranged between 1.0065 and 1.0205. The dependence on the energy and the MF strength was found to be non-linear with a maximum at 1 T and 252.7 MeV. The MC simulated values agreed with the experimentally determined correction factors within their standard deviations with a maximum difference of 0.6%. The MC calculated impact on was smaller 0.2 %. For the first time, measurements and simulations were compared for proton dosimetry within MFs using an Advanced Markus chamber. Good agreement of was found between experimentally determined and MC calculated values. The performed benchmarking of the MC code allows for calculating for various ionization chamber models, MF strengths and proton energies to generate the data needed for a proton dosimetry protocol within MFs and is, therefore, a step towardsMRiPT.

Initial Experience with the Commercial Electron FLASH Research Extension

The purpose of this study was to introduce a new commercial electron FLASH system that has the potential to become widely available for FLASH researchers globally. In this study, we first present the initial acceptance and commissioning tests for the FLASH system, and second, we highlight preliminary FLASH effect results from our cell studies. A linear accelerator was converted into a commercial research platform with the FLASH Research Extension, enabling the generation of a powerful 16 MeV electron FLASH beam. The dosimetric and stability tests were conducted using various dosimeters (i.e., radiochromic film, optically stimulated luminescent dosimeters (OSLDs), and a plane-parallel ionization chamber). To evaluate the FLASH effect, normal and cancer cell lines were FLASH irradiated using different pulse repetition frequencies (PRF) of 18 pulses/s and 180 pulses/s. The electron FLASH mode was able to generate over 1 Gy per pulse at the isocenter and a dose rate of up to 690 Gy/s near the accessory mount of the Linac gantry head. The charge collected by the plane-parallel ionization chamber at the highest PRF (i.e., 180 pulses/s) showed a linear relationship with the delivered number of pulses (i.e., 1 to 99 pulses) with a coefficient of determination (R2) of 0.9996. The absorbed dose measured using radiochromic film and OSLDs agreed within 3%, on average, and followed an inverse square law as the source-to-axis distance (SAD) varied for which the R2 values were 0.9972 and 0.9955 for radiochromic film and OSLDs, respectively. The profile of the FLASH beam was symmetrical but was not as flat as the conventional 16 MeV electron beam due to the use of a thinner custom scattering foil to reduce the degradation of the ultra-high dose rate. The depth-dose curve beyond the build-up region for the FLASH beam was similar to the conventional 16 MeV electron beam for which the range at 50% the maximum dose (R50) agreed within 0.5 mm. The FLASH beam output remained consistent over a 4-month period with a variation of 2.5%, on average. The FLASH sparing effect was observed in vitro for healthy human pancreatic cells. Furthermore, we observed that the highest PRF beam (180 pulses/s) was more effective at destroying pancreatic cancerous cells while minimizing damage to healthy cells compared to the lowest PRF beam (18 pulses/s). The novel commercial FLASH Research Extension system was dosimetrically characterized for pre-clinical FLASH research, and preliminary in vitro results demonstrated the FLASH effect. Given the prevalence of linear accelerators, this new commercial system has the potential to greatly increase the access to FLASH research.

Adaptation of a Clinical Proton Pencil Beam Scanning System for FLASH Experiments

To characterize a proton pencil beam scanning system for ultra-high dose rate (UHDR) irradiations and validate it with FLASH preclinical experiments. After modifications to the beamline to maximize the beam current at isocenter in our gantry room, we characterized the UHDR beam in terms of: 1) Size and shape of the beam spot in three configurations; pristine beam, 75 mm water-equivalent-thickness (WET) range shifter (RS), and custom-built 135 mm WET RS mounted 310 mm upstream of the aperture in the snout housing. These configurations were analyzed to determine which one achieved the highest dose rate; 2) Beam transport efficiency and beam output. We compared the signal in the monitor chambers of the proton system with a Faraday cup and plane parallel ionization chamber (PPC05, IBA dosimetry) for beam current at the cyclotron from 7.5 nA to 800 nA; 3) Dose homogeneity, beam penumbra, and dose rate for the fields to be used in preclinical irradiations. All measurements were performed at isocenter, in air or at 1 cm depth in solid water, using the highest energy (about 230 MeV), which corresponded to a nominal range of 32.9 cm in water. We modeled the UHDR beam in our treatment planning system (TPS) to optimize the dose homogeneity and lateral penumbra of the irradiation fields. We performed the preclinical experiments in single fractions of 19 Gy (RBE), 21 Gy (RBE) and 23 Gy (RBE) (RBE = 1.1), targeting the pelvis of C57BL/6 mice and using survival as the endpoint. Each arm included 6-10 mice. The proton beam was used in transmission mode, positioning the center of the mouse pelvis at isocenter, and irradiating the pelvis with a 2x6 cm^2 field. Apertures were placed at 9cm from the isocenter to sharpen the lateral penumbra. The range measurements with a multi-layer ionization chamber were consistent within 1 mm with the nominal range. In UHDR mode, the spot size at the isocenter varied from 4.5 mm for the pristine beam to 9.2 mm for the 135 mm RS. The spot size at isocenter remained constant when the beam intensity varied from 7.5 nA to 800 nA at the cyclotron exit. By employing the configuration with the 135 mm RS and optimizing the fields in the TPS, we achieved a dose rate of 1 Gy (RBE)/s for the conventional regime and 75(RBE) Gy/s for the UHDR regime. The monitor chambers of the proton system were affected by recombination at high dose rates: we observed about 35% higher output for the same number of monitor units delivered at 800 nA vs 7.5 nA. The delivered dose was determined with the PPC05 for each field, as this detector did not show recombination effects. When preclinical irradiations were independently monitored, the delivered dose was typically within 1% of the intended value. In three independent experiments, a dose of 21 Gy (RBE) or higher was associated with an increased survival in the UHDR arm compared to the conventional arm. We adapted a clinical proton system for preclinical irradiations at UHDR. Our results confirm the presence of the FLASH effect.

Diamond detectors for dose and instantaneous dose-rate measurements for ultra-high dose-rate scanned helium ion beams.

The possible emergence of the FLASH effect-the sparing of normal tissue while maintaining tumor control-after irradiations at dose-rates exceeding several tens of Gy per second, has recently spurred a surge of studies attempting to characterize and rationalize the phenomenon. Investigating and reporting the dose and instantaneous dose-rate of ultra-high dose-rate (UHDR) particle radiotherapy beams is crucial for understanding and assessing the FLASH effect, towards pre-clinical application and quality assurance programs. The purpose of the present work is to investigate a novel diamond-based detector system for dose and instantaneous dose-rate measurements in UHDR particle beams. Two types of diamond detectors, a microDiamond (PTW 60019) and a diamond detector prototype specifically designed for operation in UHDR beams (flashDiamond), and two different readout electronic chains, were investigated for absorbed dose and instantaneous dose-rate measurements. The detectors were irradiated with a helium beam of 145.7 MeV/u under conventional and UHDR delivery. Dose-rate delivery records by the monitoring ionization chamber and diamond detectors were studied for single spot irradiations. Dose linearity at 5cm depth and in-depth dose response from 2 to 16cm were investigated for both measurement chains and both detectors in a water tank. Measurements with cylindrical and plane-parallel ionization chambers as well as Monte-Carlo simulations were performed for comparisons. Diamond detectors allowed for recording the temporal structure of the beam, in good agreement with the one obtained by the monitoring ionization chamber. A better time resolution of the order of few μs was observed as compared to the approximately 50 μs of the monitoring ionization chamber. Both diamonds detectors show an excellent linearity response in both delivery modalities. Dose values derived by integrating the measured instantaneous dose-rates are in very good agreement with the ones obtained by the standard electrometer readings. Bragg peak curves confirmed the consistency of the charge measurements by the two systems. The proposed novel dosimetric system allows for a detailed investigation of the temporal evolution of UHDR beams. As a result, reliable and accurate determinations of dose and instantaneous dose-rate are possible, both required for a comprehensive characterization of UHDR beams and relevant for FLASH effect assessment in clinical treatments.

Initial experience with an electron FLASH research extension (FLEX) for the Clinac system.

Radiotherapy delivered at ultra-high-dose-rates (≥40Gy/s), that is, FLASH, has the potential to effectively widen the therapeutic window and considerably improve the care of cancer patients. The underlying mechanism of the FLASH effect is not well understood, and commercial systems capable of delivering such dose rates are scarce. The purpose of this study was to perform the initial acceptance and commissioning tests of an electron FLASH research product for preclinical studies. A linear accelerator (Clinac 23EX) was modified to include a non-clinical FLASH research extension (the Clinac-FLEX system) by Varian, a Siemens Healthineers company (Palo Alto, CA) capable of delivering a 16MeV electron beam with FLASH and conventional dose rates. The acceptance, commissioning, and dosimetric characterization of the FLEX system was performed using radiochromic film, optically stimulated luminescent dosimeters, and a plane-parallel ionization chamber. A radiation survey was conducted for which the shielding of the pre-existing vault was deemed sufficient. The Clinac-FLEX system is capable of delivering a 16MeV electron FLASH beam of approximately 1Gy/pulse at isocenter and reached a maximum dose rate >3.8Gy/pulse near the upper accessory mount on the linac gantry. The percent depth dose curves of the 16MeV FLASH and conventional modes for the 10×10cm2 applicator agreed within 0.5mm at a range of 50% of the maximum dose. Their respective profiles agreed well in terms of flatness but deviated for field sizes >10×10cm2 . The output stability of the FLASH system exhibited a dose deviation of <1%. Preliminary cell studies showed that the FLASH dose rate (180Gy/s) had much less impact on the cell morphology of 76N breast normal cells compared to the non-FLASH dose rate (18Gy/s), which induced large-size cells. Our studies characterized the non-clinical Clinac-FLEX system as a viable solution to conduct FLASH research that could substantially increase access to ultra-high-dose-rate capabilities for scientists.

An experimental setup for proton irradiation of a murine leg model for radiobiological studies

Background The purpose of this study was to introduce an experimental radiobiological setup used for in vivo irradiation of a mouse leg target in multiple positions along a proton beam path to investigate normal tissue- and tumor models with varying linear energy transfer (LET). We describe the dosimetric characterizations and an acute- and late-effect assay for normal tissue damage. Methods The experimental setup consists of a water phantom that allows the right hind leg of three to five mice to be irradiated at the same time. Absolute dosimetry using a thimble (Semiflex) and a plane parallel (Advanced Markus) ionization chamber and Monte Carlo simulations using Geant4 and SHIELD-HIT12A were applied for dosimetric validation of positioning along the spread-out Bragg peak (SOBP) and at the distal edge and dose fall-off. The mice were irradiated in the center of the SOBP delivered by a pencil beam scanning system. The SOBP was 2.8 cm wide, centered at 6.9 cm depth, with planned physical single doses from 22 to 46 Gy. The biological endpoint was acute skin damage and radiation-induced late damage (RILD) assessed in the mouse leg. Results The dose–response curves illustrate the percentage of mice exhibiting acute skin damage, and at a later point, RILD as a function of physical doses (Gy). Each dose–response curve represents a specific severity score of each assay, demonstrating a higher ED50 (50% responders) as the score increases. Moreover, the results reveal the reversible nature of acute skin damage as a function of time and the irreversible nature of RILD as time progresses. Conclusions We want to encourage researchers to report all experimental details of their radiobiological setups, including experimental protocols and model descriptions, to facilitate transparency and reproducibility. Based on this study, more experiments are being performed to explore all possibilities this radiobiological experimental setup permits.