On the acceptance, commissioning, and quality assurance of electron FLASH units.

Background & Purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an example of commissioning. Methods: A protocol for acceptance, commissioning, and QA of UHDR linear accelerators was established by combining and adapting standards and professional recommendations for standard linear accelerators based on the experience with UHDR at four clinical centers that use different UHDR devices. Non-standard dosimetric beam parameters considered included pulse width, pulse repetition frequency, dose per pulse, and instantaneous dose rate, together with recommendations on how to acquire these measurements. Results: The 6- and 9-MeV beams of an UHDR electron device were commissioned by using this developed protocol. Measurements were acquired with a combination of ion chambers, beam current transformers (BCTs), and dose-rate-independent passive dosimeters. The unit was calibrated according to the concept of redundant dosimetry using a reference setup. Conclusions: This study provides detailed recommendations for the acceptance testing, commissioning, and routine QA of low-energy electron UHDR linear accelerators. The proposed framework is not limited to any specific unit, making it applicable to all existing eFLASH units in the market. Through practical insights and theoretical discourse, this document establishes a benchmark for the commissioning of UHDR devices for clinical use.

Multi-Institutional Audit of FLASH and Conventional Dosimetry With a 3D Printed Anatomically Realistic Mouse Phantom.

PURPOSE: We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3-dimensional (3D) printed mouse phantom. METHODS AND MATERIALS: A computed tomography (CT) scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene (∼1.02 g/cm3) and polylactic acid (∼1.24 g/cm3) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid (∼0.64 g/cm3). Hounsfield units (HU), densities, and print-to-print stability of the phantoms were assessed. Three institutions were each provided a phantom and each institution performed 2 replicates of irradiations at selected anatomic regions. The average dose difference between FLASH and CONV dose distributions and deviation from the prescribed dose were measured with radiochromic film. RESULTS: Compared with the reference CT scan, CT scans of the phantom demonstrated mass density differences of 0.10 g/cm3 for bone, 0.12 g/cm3 for lung, and 0.03 g/cm3 for soft tissue regions. Differences in HU between phantoms were <10 HU for soft tissue and bone, with lung showing the most variation (54 HU), but with minimal effect on dose distribution (<0.5%). Mean differences between FLASH and CONV decreased from the first to the second replicate (4.3%-1.2%), and differences from the prescribed dose decreased for both CONV (3.6%-2.5%) and FLASH (6.4%-2.7%). Total dose accuracy suggests consistent pulse dose and pulse number, although these were not specifically assessed. Positioning variability was observed, likely due to the absence of robust positioning aids or image guidance. CONCLUSIONS: This study marks the first dosimetric audit for FLASH using a nonhomogeneous phantom, challenging conventional calibration practices reliant on homogeneous phantoms. The comparison protocol offers a framework for credentialing multi-institutional studies in FLASH preclinical research to enhance reproducibility of biologic findings.

Technical note: High-dose and ultra-high dose rate (UHDR) evaluation of Al2 O3 :C optically stimulated luminescent dosimeter nanoDots and powdered LiF:Mg,Ti thermoluminescent dosimeters for radiation therapy applications.

BACKGROUND: Dosimetry in ultra-high dose rate (UHDR) electron beamlines poses a significant challenge owing to the limited usability of standard dosimeters in high dose and high dose-per-pulse (DPP) applications. PURPOSE: In this study, Al2 O3 :C nanoDot optically stimulated luminescent dosimeters (OSLDs), single-use powder-based LiF:Mg,Ti thermoluminescent dosimeters (TLDs), and Gafchromic EBT3 film were evaluated at extended dose ranges (up to 40 Gy) in conventional dose rate (CONV) and UHDR beamlines to determine their usability for calibration and dose verification in the setting of FLASH radiation therapy. METHODS: OSLDs and TLDs were evaluated against established dose-rate-independent Gafchromic EBT3 film with regard to the potential influence of mean dose rate, instantaneous dose rate, and DPP on signal response. The dosimeters were irradiated at CONV or UHDR conditions on a 9-MeV electron beam. Under UHDR conditions, different settings of pulse repetition frequency (PRF), pulse width (PW), and pulse amplitude were used to characterize the individual dosimeters' response in order to isolate their potential dependencies on dose, dose rate, and DPP. RESULTS: The OSLDs, TLDs, and Gafchromic EBT3 film were found to be suitable at a dose range of up to 40 Gy without any indication of saturation in signal. The response of OSLDs and TLDs in UHDR conditions were found to be independent of mean dose rate (up to 1440 Gy/s), instantaneous dose rate (up to 2 MGy/s), and DPP (up to 7 Gy), with uncertainties on par with nominal values established in CONV beamlines (± 4%). In cross-comparing the response of OSLDs, TLDs and Gafchromic film at dose rates of 0.18-245 Gy/s, the coefficient of variation or relative standard deviation in the measured dose between the three dosimeters (inter-dosimeter comparison) was found to be within 2%. CONCLUSIONS: We demonstrated the dynamic range of OSLDs, TLDs, and Gafchromic film to be suitable up to 40 Gy, and we developed a protocol that can be used to accurately translate the measured signal in each respective dosimeter to dose. OSLDs and powdered TLDs were shown to be viable for dosimetric measurement in UHDR beamlines, providing dose measurements with accuracies on par with Gafchromic EBT3 film and their concurrent use demonstrating a means for redundant dosimetry in UHDR conditions.

Multi-Institutional Audit of FLASH and Conventional Dosimetry with a 3D-Printed Anatomically Realistic Mouse Phantom.

We conducted a multi-institutional audit of dosimetric variability between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3D-printed mouse phantom. A CT scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene ($~1.02 g/cm^3$) and polylactic acid ($~1.24 g/cm^3$) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid ($~0.64 g/cm^3$). Hounsfield units (HU) and densities were compared with the reference CT scan of the live mouse. Print-to-print reproducibility of the phantom was assessed. Three institutions were each provided a phantom, and each institution performed two replicates of irradiations at selected mouse anatomic regions. The average dose difference between FLASH and CONV dose distributions and deviation from the prescribed dose were measured with radiochromic film. Compared to the reference CT scan, CT scans of the phantom demonstrated mass density differences of $0.10 g/cm^3$ for bone, $0.12 g/cm^3$ for lung, and $0.03 g/cm^3$ for soft tissue regions. Between phantoms, the difference in HU for soft tissue and bone was <10 HU from print to print. Lung exhibited the most variation (54 HU) but minimally affected dose distribution (<0.5% dose differences between phantoms). The mean difference between FLASH and CONV from the first replicate to the second decreased from 4.3% to 1.2%, and the mean difference from the prescribed dose decreased from 3.6% to 2.5% for CONV and 6.4% to 2.7% for FLASH. The framework presented here is promising for credentialing of multi-institutional studies of FLASH preclinical research to maximize the reproducibility of biological findings.

Dual beam-current transformer design for monitoring and reporting of electron ultra-high dose rate (FLASH) beam parameters.

PURPOSE: To investigate the usefulness and effectiveness of a dual beam-current transformer (BCTs) design to monitor and record the beam dosimetry output and energy of pulsed electron FLASH (eFLASH) beams in real-time, and to inform on the usefulness of this design for future eFLASH beam control. METHODS: Two BCTs are integrated into the head of a FLASH Mobetron system, one located after the primary scattering foil and the other downstream of the secondary scattering foil. The response of the BCTs was evaluated individually to monitor beam output as a function of dose, scattering conditions, and ability to capture physical beam parameters such as pulse width (PW), pulse repetition frequency (PRF), and dose per pulse (DPP), and in combination to determine beam energy using the ratio of the lower-to-upper BCT signal. RESULTS: A linear relationship was observed between the absorbed dose measured on Gafchromic film and the BCT signals for both the upper and lower BCT (R2  > 0.99). A linear relationship was also observed in the BCT signals as a function of the number of pulses delivered regardless of the PW, DPP, or PRF (R2  > 0.99). The lower-to-upper BCT ratio was found to correlate strongly with the energy of the eFLASH beam due to differential beam attenuation caused by the secondary scattering foil. The BCTs were also able to provide accurate information about the PW, PRF, energy, and DPP for each individual pulse delivered in real-time. CONCLUSION: The dual BCT system integrated within the FLASH Mobetron was shown to be a reliable monitoring system able to quantify accelerator performance and capture all essential physical beam parameters on a pulse-by-pulse basis, and the ratio between the two BCTs was strongly correlated with beam energy. The fast signal readout and processing enables the BCTs to provide real-time information on beam output and energy and is proposed as a system suitable for accurate beam monitoring and control of eFLASH beams.