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

Montay‐Gruel, Pierre; Bouchet, Audrey; Jaccard, Maud; Patin, David; Serduc, Raphaël; Aim, Warren; Petersson, Kristoffer; Petit, Benoît; Bailat, Claude; Bourhis, Jean; Bräuer-Krisch, Elke; Vozenin, Marie-Catherine

doi:10.1016/j.radonc.2018.08.016

Cited by 276 publications

(270 citation statements)

References 36 publications

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“…In whole mouse brain irradiated to 10 Gy, spatial memory was preserved for FLASH dose rates >100 Gy/s and partially preserved down to ~30 Gy/s, while total impairment was observed at conventional (0.1 Gy/s) dose rates . This neurocognitive sparing effect was subsequently observed using synchrotron‐generated x rays delivered with a FLASH‐compatible mean dose‐rate of 37 Gy/s . In higher mammalian subjects, including mini pigs and cats, the FLASH effect was again demonstrated by way of a significant reduction in normal tissue toxicity relative to conventional treatments even as dose escalation was performed.…”

Section: Introductionmentioning

confidence: 95%

“…13,15 In principal, modern clinical linacs can be made suitable for FLASH therapy, but this requires substantial modification to these clinically optimized systems. 16,17 Moreover, while synchrotrons, notable for their superior beam intensities, 14,18,19 and high-energy cyclotron-accelerated protons are also capable of achieving the requisite dose rates, 20 limited accessibility and high costs remain barriers to their widespread application.…”

Section: Introductionmentioning

confidence: 99%

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On the capabilities of conventional x‐ray tubes to deliver ultra‐high (FLASH) dose rates

Bazalova‐Carter

Esplen

2019

Medical Physics

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Purpose By means of Monte Carlo (MC) simulations and indirect measurements, we have evaluated the maximum dose rates achievable with conventional x‐ray tubes and related them to FLASH therapy dose rates of >40 Gy/s. Methods Monte Carlo models of two 160 kV x‐ray tubes, the 3‐kW MXR‐160/22 and the 6‐kW MXR‐165, were built in the EGSnrc/BEAMnrc code. The dose rate in a water phantom placed against the x‐ray tube surface, located at 3.7 and 3.5 cm from the focal spot for the MXR‐160/22 and MXR‐165 x‐ray tube, respectively, was calculated with DOSXYZnrc. Dose delivered with the 120‐kV beam in a plastic water phantom for the MXR‐160/22 was measured and calculated. Gafchromic EBT3 films were placed at 15 and 18 mm depths in the plastic water phantom that was irradiated with a low tube current of 0.2 mA for 30 s. Results The maximum 160‐kV phantom surface dose rate was determined to be FLASH capable, calculated as (114.3 ± 0.6) Gy/s and (160.0 ± 0.8) Gy/s for the MXR‐160/22 and MXR‐165 x‐ray tubes, respectively. The dose rate in a 1‐cm diameter region was found to be (110.6 ± 2.8) Gy/s and (151.9 ± 2.6) Gy/s and remained FLASH capable to depths of 1.4 and 2.0 mm for the MXR‐160/22 and MXR‐165 x‐ray tube, respectively. The 120‐kV dose profiles measured with EBT3 films agreed with MC simulations to within 3.6% for regions outside of heel effect and at both measurement depths; this presented a good validation data set for the simulations of phantom surface dose rate using the 160‐kV beam. Conclusions We have indirectly determined that, with a careful experimental design, conventional x‐ray tubes can be made suitable for use in FLASH radiotherapy and dosimetry experiments.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

On the capabilities of conventional x‐ray tubes to deliver ultra‐high (FLASH) dose rates

Bazalova‐Carter

Esplen

2019

Medical Physics

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“…The phenomenon of the increased therapeutic index of FLASH compared to conventional dose rate irradiation, or the “FLASH effect,” has now been reported in multiple preclinical models. Normal tissue sparing by FLASH of multiple organ systems including lung, brain, intestinal tract, and skin has been demonstrated in multiple mouse strains and even additional species (cat and mini‐pig), while demonstrating an equivalent (and in some cases superior) tumoricidal effect relative to conventional dose‐rate delivery in multiple in vivo tumor models . Given the nascent state of the field, a large portion of experimental observations to date remain preliminary and unpublished, and many questions remain unanswered particularly with respect to mechanism.…”

Section: For the Proposition: Peter G Maxim Phdmentioning

confidence: 99%

“…To date, preclinical FLASH irradiation of small animals and small superficial targets in larger animals has been possible using modifications of existing irradiation systems that are capable of producing FLASH dose rates when limited to small volumes (of up to a few cubic centimeters), including electron linear accelerators, a synchrotron light source producing kilovoltage energy x rays, and certain proton accelerators …”

Section: For the Proposition: Peter G Maxim Phdmentioning

confidence: 99%

“…Cs‐137 photons deliver higher doses outside of the tumor, whereas 4.5 MeV electrons have lower surface dose and higher central dose in mice. In another study, the results of square conventional beams were compared with FLASH circular beams, albeit of similar equivalent field size . Every FLASH study should be carefully reviewed to evaluate the impact of these differences, in addition to dose rate, on the results.…”

Section: Against the Proposition: Paul Keall Phdmentioning

confidence: 99%

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FLASH radiotherapy: Newsflash or flash in the pan?

Maxim

Keall

Cai³

2019

Medical Physics

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Implementation and validation of a beam‐current transformer on a medical pulsed electron beam LINAC for FLASH‐RT beam monitoring

Oesterle

Jorge

Grilj

et al. 2021

J Applied Clin Med Phys

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To implement and validate a beam current transformer as a passive monitoring device on a pulsed electron beam medical linear accelerator (LINAC) for ultra-high dose rate (UHDR) irradiations in the operational range of at least 3 Gy to improve dosimetric procedures currently in use for FLASH radiotherapy (FLASH-RT) studies. Methods: Two beam current transformers (BCTs) were placed at the exit of a medical LINAC capable of UHDR irradiations. The BCTs were validated as monitoring devices by verifying beam parameters consistency between nominal values and measured values, determining the relationship between the charge measured and the absorbed dose, and checking the short-and long-term stability of the charge-absorbed dose ratio. Results:The beam parameters measured by the BCTs coincide with the nominal values. The charge-dose relationship was found to be linear and independent of pulse width and frequency. Short-and long-term stabilities were measured to be within acceptable limits. Conclusions: The BCTs were implemented and validated on a pulsed electron beam medical LINAC, thus improving current dosimetric procedures and allowing for a more complete analysis of beam characteristics. BCTs were shown to be a valid method for beam monitoring for UHDR (and therefore FLASH) experiments.

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

Cited by 276 publications

References 36 publications

On the capabilities of conventional x‐ray tubes to deliver ultra‐high (FLASH) dose rates

On the capabilities of conventional x‐ray tubes to deliver ultra‐high (FLASH) dose rates

FLASH radiotherapy: Newsflash or flash in the pan?

Implementation and validation of a beam‐current transformer on a medical pulsed electron beam LINAC for FLASH‐RT beam monitoring

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