Maud Jaccard

Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s

This study shows for the first time that normal brain tissue toxicities after WBI can be reduced with increased dose rate. Spatial memory is preserved after WBI with mean dose rates above 100Gy/s, whereas 10Gy WBI at a conventional radiotherapy dose rate (0.1Gy/s) totally impairs spatial memory.

Commissioning of the Leksell Gamma Knife® Icon™

Purpose: The Leksell Gamma Knife (LGK) Icon has been recently introduced to provide Gamma Knife technology with frameless stereotactic treatments which use an additional cone‐beam CT (CBCT) imaging system and a motion tracking system (IFMM, Intra‐Fraction Motion Management). The system was commissioned for the treatment unit itself as well as the imaging system. Methods: The LGK Icon was calibrated using an A1SL ionization chamber. EBT3 radiochromic films were employed to independently check the machine calibration, to measure the relative output factors (ROFs) and to collect dose distributions. Coincidence between CBCT isocenter and radiological focus was evaluated by means of EBT3 films. CBCT image quality was investigated in terms of spatial resolution, contrast‐to‐noise ratio (CNR), and uniformity for the two presets available (low dose and high dose). Computed Tomography Dose Index (CTDI) was also measured for both presets. Results: The absolute dose rate of the LGK Icon was 3.86 ± 0.09 Gy/min. This result was confirmed by EBT3 readings. ROF were found to be 0.887 ± 0.035 and 0.797 ± 0.032 for the 8 mm and 4 mm collimators, respectively, which are within 2% of the Monte Carlo‐derived ROF values. Excellent agreement was found between calculated and measured dose distribution with the gamma pass rate >95% of points for the nine dose distributions analyzed with 3%/1 mm criteria. CBCT isocenter was found to be within 0.2 mm with respect to radiological focus. Image quality parameters were found to be well within the manufacturers specifications with the high‐dose preset being superior in terms of CNR and uniformity. CTDI values were 2.41 mGy and 6.32 mGy, i.e. −3.6% and 0.3% different from the nominal values for the low‐dose and high‐dose presets, respectively. Conclusions: The LGK Icon was successfully commissioned for clinical use. The use of the EBT3 to characterize the treatment unit was demonstrated to be feasible. The CBCT imaging system operates well within the manufacturers specifications and provides good geometrical accuracy.

High dose‐per‐pulse electron beam dosimetry – A model to correct for the ion recombination in the Advanced Markus ionization chamber

Purpose: The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose‐per‐pulse electron beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two‐voltage‐analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen. Methods: Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source‐to‐surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose–response, in beams with varying dose rate/dose‐per‐pulse, with the chamber together with dose rate/dose‐per‐pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose‐per‐pulse (10−2 ≤ mean dose rate ≤ 103 Gy/s, 102 ≤ mean dose rate within pulse ≤ 107 Gy/s, 10−4 ≤ dose‐per‐pulse ≤ 101 Gy), which was achieved by independently varying the linac gun grid tension, and the SSD. Results: The results demonstrate how the ion collection efficiency of the chamber decreased as the dose‐per‐pulse increased, and that the ion recombination was dependent on the dose‐per‐pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose‐per‐pulse range, but only for a low polarizing chamber voltage (50 V). However, the two‐voltage‐analysis method and the Burns & McEwen equation only agreed with the data at low dose‐per‐pulse values (≤ 10−2 and ≤ 10−1 Gy, respectively). An empirical model of the ion recombination in the chamber was found by fitting a logistic function to the data. Conclusions: The ion collection efficiency of the Advanced Markus ionization chamber decreases for measurements in electron beams with increasingly higher dose‐per‐pulse. However, this chamber is still functional for dose measurements in beams with dose‐per‐pulse values up toward and above 10 Gy, if the ion recombination is taken into account. Our results show that existing models give a less‐than‐accurate description of the observed ion recombination. This motivates the use of the presented empirical model for measurements with the Advanced Markus chamber in high dose‐per‐pulse electron beams, as it enables accurate absorbed dose measurements (uncertainty estimation: 2.8–4.0%, k = 1). The model depends on the dose‐per‐pulse in the beam, and it is also influenced by the polarizing chamber voltage, with increasing ion recombination with a lowering of the voltage.

High dose‐per‐pulse electron beam dosimetry: Usability and dose‐rate independence of EBT3 Gafchromic films

Purpose: The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose‐per‐pulse linear accelerator (linac), capable of delivering electron beams with a mean dose‐rate (Dm) ranging from 0.07 to 3000 Gy/s and a dose‐rate in pulse (Dp) of up to 8 × 106 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose‐rate dependence of their response. Material and methods: Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Dm dependence was studied at the clinical linac by changing the pulse repetition frequency (f) of the beam in order to vary Dm between 0.55 and 4.40 Gy/min, while Dp dependence was probed at the prototype machine for Dp ranging from 7 × 103 to 8 × 106 Gy/s. Dp dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo‐luminescent dosimeters (TLD) that have been reported as being dose‐rate independent up to such high dose‐rates. Results: We report that uncertainty below 4% (k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Dm dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Dp range attainable at the prototype linac confirming the absence of any dose‐rate dependence within the investigated range (7 × 103 to 8 × 106 Gy/s). This aspect was further corroborated by the linear relationship between the dose‐per‐pulse (Dp) measured by films and the charge per pulse (Cp) measured at the prototype linac exit. Conclusion: Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% (k = 2) and are dose‐rate and energy independent.

Probing the Kinetic Parameters of Plutonium-Naturally Occurring Organic Matter Interactions in Freshwaters Using the Diffusive Gradients in Thin Films Technique.

The interaction of trace metals with naturally occurring organic matter (NOM) is a key process of the speciation of trace elements in aquatic environments. The rate of dissociation of metal-NOM complexes will impact the amount of free metal available for biouptake. Assessing the bioavailability of plutonium (Pu) helps to predict its toxic effects on aquatic biota. However, the rate of dissociation of Pu-NOM complexes in natural freshwaters is currently unknown. Here, we used the technique of diffusive gradients in thin films (DGT) with several diffusive layer thicknesses to provide new insights into the dissociation kinetics of Pu-NOM complexes. Results show that Pu complexes with NOM (mainly fulvic acid) are somewhat labile (0.2 ≤ ξ ≤ 0.4), with kd = 7.5 × 10(-3) s(-1). DGT measurements of environmental Pu in organic-rich natural water confirm these findings. In addition, we determined the effective diffusion coefficients of Pu(V) in polyacrylamide (PAM) gel in the presence of humic acid using a diffusion cell (D = 1.70 ± 0.25 × 10(-6) cm(2) s(-1)). These results show that Pu(V) is a more mobile species than Pu(IV).

The advantage of Flash radiotherapy confirmed in mini-pig and cat-cancer patients

Purpose: Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. Experimental Design: Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called “FLASH-RT” and irradiation delivered at a conventional dose rate called “Conv-RT.” A clinical, phase I, single-dose escalation trial (25–41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT. Results: Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%. Conclusions: Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients. See related commentary by Harrington, p. 3

X-rays can trigger the FLASH effect: Ultra-high dose-rate synchrotron light source prevents normal brain injury after whole brain irradiation in mice

This study is the first proof of concept that the FLASH effect can be triggered by X-rays. Our results show that a 10 Gy whole-brain irradiation delivered at ultra-high dose-rate with synchrotron generated X-rays does not induce memory deficit; it reduces hippocampal cell-division impairment and induces less reactive astrogliosis.