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Ultrahigh-dose rate X-ray platform lines up for FLASH radiobiological research

23 Feb 2024
Nolan Esplen at the FLASH Irradiation Research Station at TRIUMF

Researchers in Canada have characterized an X-ray irradiation platform for radiobiological studies of FLASH radiotherapy – an emerging cancer treatment technique that uses ultrahigh-dose rate (UHDR) irradiation. The platform, dubbed FLASH Irradiation Research Station at TRIUMF, or “FIRST”, can deliver 10 MV X-ray beams at dose rates exceeding 100 Gy/s.

Located at the ARIEL beamline at TRIUMF, Canada’s particle accelerator centre, FIRST is currently the only irradiation platform of its kind in North America. Globally, there are two experimental UHDR megavoltage X-ray beamlines: the one at TRIUMF in Vancouver and another in Chengdu, at the China Academy of Engineering Physics terahertz free electron laser.

Megavoltage X-rays require modest accelerator specifications when compared with other modalities used to treat deep-seated tumours, the researchers say, and FIRST can offer both UHDR and conventional megavoltage irradiations on a common beamline.

“There’s a gap in the availability of ultrahigh-dose rate X-ray sources; it’s kind of an unmet need in the field, and there’s no commercial platform available to deliver this type of radiation routinely,” explains Nolan Esplen, a postdoctoral researcher at MD Anderson Cancer Center. “This multi-year collaborative project [with TRIUMF] …was an opportunity for leveraging this unique laboratory with access to a high-energy superconducting electron linac to produce the type of radiation we want to look at for FLASH radiobiological research.”

Esplen conducted FIRST characterization experiments while he was a graduate student at the University of Victoria working in the XCITE Lab. The research team’s latest study, published in Nature Scientific Reports, presents a comprehensive characterization of FIRST and initial preclinical experiments. Simulation work was published in 2022 in Physics in Medicine & Biology.

“We have been involved in ultrahigh-dose rate irradiations for quite some time now,” says XCITE Lab director Magdalena Bazalova-Carter. “We started talking with people at TRIUMF about the ARIEL beamline, and how if we built a target for this beamline, what kind of X-ray dose rates would we be getting. That’s how it all started.”

FIRST’s firsts

The researchers explored a subset of available and clinically relevant beam parameters to characterize FIRST under UHDR and conventional dose-rate operation. They fixed the electron beam energy at 10 MeV to maximize dose rates and target longevity, and set the beam current (peak current) between 95 and 105 µA. Dose rates were calculated using film dosimetry.

Dose rates above 40 Gy/s were achieved at up to 4.1 cm depth for a 1-cm field size. Compared with a clinical 10 MV beam, FIRST offered a reduced superficial dose buildup. Relative to low-energy electron sources, FIRST offered a more gradual dose fall-off beyond dmax (the depth of maximum dose). The team notes that the presence of steep superficial depth–dose gradients led to dose heterogeneity issues that currently restrict applications to preclinical work. Source stability limitations led to variations in current and dose.

Informed by the characterization studies, the researchers then used FIRST to deliver UHDR (above 80 Gy/s) and low-dose rate conventional X-ray irradiation to the lungs of healthy mice. They successfully delivered doses of 15 and 30 Gy to within 10% of the prescription at 1-cm depth. Effects of lung tissue inhomogeneities were not corrected for (the group’s design study pointed to negligible perturbations at megavoltage beam energies). Electron source output and film dosimetry variance dominated the uncertainties in pre-treatment dose measurements.

Lessons learned

The physical space in which FIRST is located was originally purposed – and still serves as – a beam dump (where a beam of charged particles can be safely absorbed). That led to some unique design challenges for FIRST.

“There was no basis for doing what we were doing, and it was also a development opportunity for TRIUMF. A lot of people learned about the system, as well as the nuances for this type of delivery and things that we did well, and what we could do better in the future,” Esplen says. “With the fact that this is a facility that is being developed, we were a first science opportunity – it’s a very dynamic environment. We have some extremely talented collaborators and beam physicists who worked to set all the optics parameters of the beamlines so that we could deliver a minimally dispersive beam of correct size at the target.”

At the time of the researchers’ experiments, only one phantom pair or a single mouse could be irradiated every 45 min after accounting for platform setup, delivery and shutdown. And after every adjustment made to the beamline and the beam itself, the researchers had to retune the beam to confirm its output and dosimetry.

“It’s a different story from clinical medical physics. When you run experiments on a linac in a hospital, one person can handle the entire experiment…This is a very different situation,” says Bazalova-Carter. “Five people had to run the beamline [for these experiments] to monitor all the screens – and while by far not all of them were used for our experiments, I think I counted 113 screens in the control room…It was quite interesting that we could get very decent dose agreement between Monte Carlo simulations and experiments, given how challenging these experiments are.”

Such hurdles notwithstanding, advantages of the FIRST platform include control over key source parameters, including pulse repetition frequency, peak current, beam energy and average power.

“We were the first user of the ARIEL beamline,” Bazalova-Carter reflects. “It was extremely satisfying, after many years of working on this project, to actually be able to run mouse irradiation experiments.”

A radiobiological follow-up study is forthcoming.

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