Dosimetric and biologic intercomparison between electron and proton FLASH beams.

BACKGROUND AND PURPOSE: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at an average dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by eFLASHvs. pFLASH has yet been performed and constitutes the aim of the present study. MATERIALS AND METHODS: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥110 Gy/s eFLASH and pFLASH) dose rates. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed using previously validated dosimetric approaches and experimental murine models. RESULTS: The difference between the average absorbed dose measured at Gantry 1 with PSI reference dosimeters and with CHUV/IRA dosimeters was -1.9 % (0.1 Gy/s) and + 2.5 % (110 Gy/s). The neurocognitive capacity of eFLASH and pFLASH irradiated mice was indistinguishable from the control, while both eCONV and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained after an ablative dose of 20 Gy delivered with the two beams at CONV and FLASH dose rates. Tumor rejection upon rechallenge indicates that anti-tumor immunity was activated independently of the beam-type and the dose-rate. CONCLUSION: Despite major differences in the temporal microstructure of proton and electron beams, this study shows that dosimetric standards can be established. Normal brain protection and tumor control were produced by the two beams. More specifically, normal brain protection was achieved when a single dose of 10 Gy was delivered in 90 ms or less, suggesting that the most important physical parameter driving the FLASH sparing effect might be the mean dose rate. In addition, a systemic anti-tumor immunological memory response was observed in mice exposed to high ablative dose of electron and proton delivered at CONV and FLASH dose rate.

Dosimetric and biologic intercomparison between electron and proton FLASH beams.

Background and purpose: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at a mean dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by e vs. pFLASH has yet been performed and constitutes the aim of the present study. Materials and methods: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥100 Gy/s eFLASH and pFLASH) irradiation. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed with previously validated models. Results: Doses measured at Gantry1 were in agreement (± 2.5%) with reference dosimeters calibrated at CHUV/IRA. The neurocognitive capacity of e and pFLASH irradiated mice was indistinguishable from the control while both e and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained with the two beams and was similar between e and pFLASH vs. e and pCONV. Tumor rejection was similar indicating that T-cell memory response is beam-type and dose-rate independent. Conclusion: Despite major differences in the temporal microstructure, this study shows that dosimetric standards can be established. The sparing of brain function and tumor control produced by the two beams were similar, suggesting that the most important physical parameter driving the FLASH effect is the overall time of exposure which should be in the range of hundreds of milliseconds for WBI in mice. In addition, we observed that immunological memory response is similar between electron and proton beams and is independent off the dose rate.

Characterization of LiF:Mg,Ti thermoluminescence detectors in low-LET proton beams at ultra-high dose rates.

Objective.This work aims at characterizing LiF:Mg,Ti thermoluminescence detectors (TLDs) for dosimetry of a 250 MeV proton beam delivered at ultra-high dose rates (UHDR). Possible dose rate effects in LiF:Mg,Ti, as well as its usability for dosimetry of narrow proton beams are investigated.Approach.LiF:Mg,Ti (TLD-100TMMicrocubes, 1 mm × 1 mm × 1 mm) was packaged in matrices of 5 × 5 detectors. The center of each matrix was irradiated with single-spot low-LET (energy >244 MeV) proton beam in the (1-4500) Gy s-1average dose rates range. A beam reconstruction procedure was applied to the detectors irradiated at the highest dose rate (Gaussian beam sigma <2 mm) to correct for volumetric averaging effects. Reference dosimetry was carried out with a diamond detector and radiochromic films. The delivered number of protons was measured by a Faraday cup, which was employed to normalize the detector responses.Main results.The lateral beam spread obtained from the beam reconstruction agreed with the one derived from the radiochromic film measurements. No dose rates effects were observed in LiF:Mg,Ti for the investigated dose rates within 3% (k= 1). On average, the dose response of the TLDs agreed with the reference detectors within their uncertainties. The largest deviation (-5%) was measured at 4500 Gy s-1.Significance.The dose rate independence of LiF:Mg,Ti TLDs makes them suitable for dosimetry of UHDR proton beams. Additionally, the combination of a matrix of TLDs and the beam reconstruction can be applied to determine the beam profile of narrow proton beams.

Ultra-high dose rate dosimetry for pre-clinical experiments with mm-small proton fields.

PURPOSE: To characterize an experimental setup for ultra-high dose rate (UHDR) proton irradiations, and to address the challenges of dosimetry in millimetre-small pencil proton beams. METHODS: At the PSI Gantry 1, high-energy transmission pencil beams can be delivered to biological samples and detectors up to a maximum local dose rate of âˆ¼9000 Gy/s. In the presented setup, a Faraday cup is used to measure the delivered number of protons up to ultra-high dose rates. The response of transmission ion-chambers, as well as of different field detectors, was characterized over a wide range of dose rates using the Faraday cup as reference. RESULTS: The reproducibility of the delivered proton charge was better than 1 % in the proposed experimental setup. EBT3 films, Al2O3:C optically stimulated luminescence detectors and a PTW microDiamond were used to validate the predicted dose. Transmission ionization chambers showed significant volume ion-recombination (>30 % in the tested conditions) which can be parametrized as a function of the maximum proton current density. Over the considered range, EBT3 films, inorganic scintillator-based screens and the PTW microDiamond were demonstrated to be dose rate independent within ±3 %, ±1.8 % and ±1 %, respectively. CONCLUSIONS: Faraday cups are versatile dosimetry instruments that can be used for dose estimation, field detector characterization and on-line dose verification for pre-clinical experiments in UHDR proton pencil beams. Among the tested detectors, the commercial PTW microDiamond was found to be a suitable option to measure real time the dosimetric properties of narrow pencil proton beams for dose rates up to 2.2 kGy/s.

Faraday cup for commissioning and quality assurance for proton pencil beam scanning beams at conventional and ultra-high dose rates.

Recently, proton therapy treatments delivered with ultra-high dose rates have been of high scientific interest, and the Faraday cup (FC) is a promising dosimetry tool for such experiments. Different institutes use different FC designs, and either a high voltage guard ring, or the combination of an electric and a magnetic field is employed to minimize the effect of secondary electrons. The authors first investigate these different approaches for beam energies of 70, 150, 230 and 250 MeV, magnetic fields between 0 and 24 mT and voltages between -1000 and 1000 V. When applying a magnetic field, the measured signal is independent of the guard ring voltage, indicating that this setting minimizes the effect of secondary electrons on the reading of the FC. Without magnetic field, applying the negative voltage however decreases the signal by an energy dependent factor up to 1.3% for the lowest energy tested and 0.4% for the highest energy, showing an energy dependent response. Next, the study demonstrates the application of the FC up to ultra-high dose rates. FC measurements with cyclotron currents up to 800 nA (dose rates of up to approximately 1000 Gy s-1) show that the FC is indeed dose rate independent. Then, the FC is applied to commission the primary gantry monitor for high dose rates. Finally, short-term reproducibility of the monitor calibration is quantified within single days, showing a standard deviation of 0.1% (one sigma). In conclusion, the FC is a promising, dose rate independent tool for dosimetry up to ultra-high dose rates. Caution is however necessary when using a FC without magnetic field, as a guard ring with high voltage alone can introduce an energy dependent signal offset.

Development and clinical evaluation of an ionization chamber array with 3.5 mm pixel pitch for quality assurance in advanced radiotherapy techniques.

PURPOSE: To characterize a new air vented ionization chamber technology, suitable to build detector arrays with small pixel pitch and independence of sensitivity on dose per pulse. METHODS: The prototype under test is a linear array of air vented ionization chambers, consisting of 80 pixels with 3.5 mm pixel pitch distance and a sensitive volume of about 4 mm(3). The detector has been characterized with (60)Co radiation and MV x rays from different linear accelerators (with flattened and unflattened beam qualities). Sensitivity dependence on dose per pulse has been evaluated under MV x rays by changing both the source to detector distance and the beam quality. Bias voltage has been varied in order to evaluate the charge collection efficiency in the most critical conditions. Relative dose profiles have been measured for both flattened and unflattened distributions with different field sizes. The reference detectors were a commercial array of ionization chambers and an amorphous silicon flat panel in direct conversion configuration. Profiles of dose distribution have been measured also with intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and volumetric modulated arc therapy (VMAT) patient plans. Comparison has been done with a commercial diode array and with Gafchromic EBT3 films. RESULTS: Repeatability and stability under continuous gamma irradiation are within 0.3%, in spite of low active volume and sensitivity (∼200 pC/Gy). Deviation from linearity is in the range [0.3%, -0.9%] for a dose of at least 20 cGy, while a worsening of linearity is observed below 10 cGy. Charge collection efficiency with 2.67 mGy/pulse is higher than 99%, leading to a ±0.9% sensitivity change in the range 0.09-2.67 mGy/pulse (covering all flattened and unflattened beam qualities). Tissue to phantom ratios show an agreement within 0.6% with the reference detector up to 34 cm depth. For field sizes in the range 2 × 2 to 15 × 15 cm(2), the output factors are in agreement with a thimble chamber within 2%, while with 25 × 25 cm(2) field size, an underestimation of 4.0% was found. Agreement of field and penumbra width measurements with the flat panel is of the order of 1 mm down to 1 × 1 cm(2) field size. Flatness and symmetry values measured with the 1D array and the reference detectors are comparable, and differences are always smaller than 1%. Angular dependence of the detector, when compared to measurements taken with a cylindrical chamber in the same phantom, is as large as 16%. This includes inhomogeneity and asymmetry of the design, which during plan verification are accounted for by the treatment planning system (TPS). The detector is capable to reproduce the dose distributions of IMRT and VMAT plans with a maximum deviation from TPS of 3.0% in the target region. In the case of VMAT and SRS plans, an average (maximum) deviation of the order of 1% (4%) from films has been measured. CONCLUSIONS: The investigated technology appears to be useful both for Linac QA and patient plan verification, especially in treatments with steep dose gradients and nonuniform dose rates such as VMAT and SRS. Major limitations of the present prototype are the linearity at low dose, which can be solved by optimizing the readout electronics, and the underestimation of output factors with large field sizes. The latter problem is presently not completely understood and will require further investigations.