Canadian technology start-up Medscint is working with customers to develop a new generation of real-time, small-field dosimetry solutions based on plastic scintillation detectors
Ultrahigh-dose-rate FLASH radiotherapy – whether using electron, proton or photon treatment beams – is shaping up as the “next big thing” in radiation oncology research. It’s easy to see why: a growing body of evidence – comprising preclinical experiments as well as the first small-scale clinical studies using electron and proton beams – demonstrates that radiation delivered at ultrahigh dose rates (roughly 40 Gy/s and above) can drastically reduce collateral damage and toxicity in normal healthy tissue while preserving anti-tumour activity.
Even so, it’s still early days and much work remains to be done before the at-scale clinical translation of FLASH radiotherapy becomes reality – not least the commercial development of affordable FLASH treatment machines as well as core enabling technologies such as FLASH treatment planning systems and robust dosimetry solutions for real-time beam monitoring. In the meantime, to fast-track commercial and clinical translation, medical physicists are redoubling their efforts to understand the fundamental radiobiology of the FLASH effect and, in turn, unlock research insights that will maximize the clinical impact of FLASH modalities for enhanced patient outcomes.
With this in mind, a team of scientists at the University of Victoria in British Columbia, Canada, has developed a cost-effective X-ray-tube-based system that exploits a customized beam shutter for in vitro ultrahigh-dose-rate irradiation (up to 118 Gy/s) of small samples with exposure times of less than 1 s (and latterly as short as 1 ms). Alongside the beam shutter and sample holder – which are designed and installed in close proximity to the X-ray tube window – one of the main building blocks of the benchtop system is a real-time, small-field dosimetry solution based on plastic scintillation detectors developed by Medscint, a specialist technology company in Quebec City.
“Plastic scintillation detectors are an ideal dosimeter for ultrahigh-dose-rate radiotherapy,” explains Magdalena Bazalova-Carter, lead physicist on the project and head of the X-ray Cancer Imaging and Therapy Experimental (XCITE) Lab at the University of Victoria. “By placing the scintillation detectors in close proximity of the beam shutter,” she adds, “we’ve been able to verify dose delivery and confirm that our system can accurately expose for short pulses down to 1 ms duration.”
More broadly, plastic scintillators combine near-water-equivalence, nanosecond response times and high spatial resolution with MR-Linac compatibility and robustness against radiation damage.
Another advantage of the Medscint detectors is their compact footprint (0.5 mm long, 0.5 mm diameter), which makes them ideal for small-field and multipoint dosimetry. That’s a “must-have” for Bazalova-Carter and colleagues as their X-ray tube system is optimized for uniform dose delivery across samples no bigger than 6 mm in diameter.
In the lab, the XCITE team is currently putting the prototype X-ray tube system through its paces in a series of very-small-animal experiments, irradiating fruit fly larvae with ultrahigh dose rates and tracking comparative survival versus conventional irradiation schemes. “The early results are promising,” notes Alex Hart, a PhD student within the XCITE programme, “plus we’re now looking at the possibility of adding Medscint scintillation detectors to provide real-time, online readout of dose delivery.”
Put another way: it’s all about granularity. Inserting a small radiochromic film into the sample holder while irradiating the larvae provides the dose after the fact – i.e. if the dose is off for some reason, it’s not easy to figure out the root cause. “With a plastic scintillator in there,” Hart explains, “I could see that perhaps one of the exposures of a multipulse delivery didn’t happen at all or that it was shorter than expected.”
Beyond these proof-of-concept experiments, the next step for XCITE researchers is to deploy their X-ray tube system in the irradiation of normal and cancerous skin cells fabricated with 3D printing methods. Depending on the cell line, these so-called “multicellular cell spheroids” can be grown in a uniform fashion, such that their size can be controlled to within 5% – which, in turn, results in an interspheroid dose delivery difference of less than 1.1%. “Later this spring,” explains Hart, “we’ll use the X-ray tube system to investigate normal and cancer-cell spheroid response to ultrahigh dose rates and conventional irradiations – in each case, with and without gold nanoparticles as radiosensitizers.”
Along a parallel line of enquiry, the XCITE team is also building a FLASH irradiation station on the ARIEL beamline at TRIUMF, the high-energy physics laboratory in Vancouver. To date, Bazalova-Carter, PhD student Nolan Esplen and colleagues have designed an electron-to-photon converter for the delivery of an ultrahigh dose-rate 10 MV photon beam on ARIEL’s existing medium-energy beam dump. Over the next three months, that cutting-edge capability will be evaluated in a series of experiments to investigate the FLASH effect on healthy lung tissue in mice.
Beam modelling suggests that the achieved dose rates at the irradiation site should be up to 200 Gy/s and above the FLASH effect dose-rate threshold of 40 Gy/s to depths of 10 cm. Here again, the R&D collaboration with Medscint will be pivotal. “We’ll use the Medscint plastic scintillators for in vivo dosimetry at TRIUMF, while evaluating scintillator response in the MV regime – something we haven’t done as yet,” explains Bazalova-Carter. “We’re also keen to work with the Medscint team to push the temporal resolution of the detectors further, down beyond the 1 ms exposure time into the microsecond regime.”
Looking further ahead, over the next 18–24 months, the XCITE R&D programme on spatially fractionated radiation therapy (SFRT) provides another opportunity for collaboration with Medscint’s development engineers. SFRT involves delivery of a single high dose fraction in a deliberately heterogeneous fashion – i.e. with high doses within the target volume as well as regions of underdosing – and shows great promise for the reduction of side-effects while maintaining efficacy for killing tumour cells. “We are developing custom hardware for SFRT beam delivery,” concludes Bazalova-Carter, “but we’re interested to see what we can achieve in partnership with Medscint on innovative SFRT dosimetry solutions.”
D Cecchi et al. 2021 Characterization of an X-ray-tube-based ultrahigh-dose-rate system for in vitro irradiations Med. Phys. 48 7399
Putting the emphasis on customer collaboration
François Therriault-Proulx, president and CEO of Medscint, was one of the company’s co-founders in 2016, along with colleagues Simon Girard (chief science and technology officer) and Jonathan Turcotte (chief product, sales and marketing officer).
Before taking what he calls the “entrepreneurship leap of faith”, Therriault-Proulx spent eight years as an academic scientist working on the fundamentals of scintillation dosimetry, spanning PhD and postdoctoral research positions at Université Laval, Quebec City, and the University of Texas MD Anderson Cancer Center, Houston. Here, he gives Physics World the headline take on Medscint’s technology and commercial offering.
What does Medscint’s addressable market look like?
Our mission at Medscint is to deliver best-in-class small-field dosimeters based on our proprietary optical know-how in the field of plastic scintillation detectors. To date, we’ve positioned our initial product – the HYPERSCINT Research Platform – with the cross-disciplinary R&D teams working to realize next-generation radiation therapy systems. This year, however, we’ll diversify with the launch of our first US Food and Drug Administration (FDA)-registered clinical system for small-field dosimetry applications in machine QA.
Following the eye-catching results presented by our customers at high-profile medical physics conferences – including last year’s AAPM Annual Meeting – we will also shortly be launching a dedicated product to bring ultrahigh-dose-rate dosimetry to the next level. Specifically, the HYPERSCINT FLASH research platform will enable linac pulse counting and dose-per-pulse measurement to support ultrahigh-dose-rate irradiation schemes.
Why are scintillation detectors a good fit for small-field dosimetry?
Plastic scintillators have a lot to offer as treatment fields get smaller and geometrically more complex. With no need for small-field correction factors to characterize device behaviour, our detectors provide a real-time measurement tool that combines high linearity with respect to dose and dose rate. That wide linear dynamic range is relevant at both ends of the treatment spectrum, whether for novel low-dose-rate irradiation schemes or ultrahigh-dose-rate FLASH applications.
How important are customers in shaping product innovation at Medscint?
As a new-entrant technology company, it’s essential that we’re there to support our customers, listening to their needs and responding proactively. We have a collaborative relationship with our customers and research partners, with their feedback shaping product iteration and the longer-term innovation roadmap.
It’s worth adding that Medscint was founded on a true willingness to generate a positive impact on society through innovations that could be easily segued from the research sector to the market. We view Medscint as something of a “connector”, building a network between our partners to help us refine and innovate our technologies versus their evolving needs. It’s thanks to this network that we’ll be able to advance the fields of scintillation, optical dosimetry and ultimately cancer care.