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

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 $\ge$ 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 $\le$ 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 $\pm$ 2%.