Research

Project	Lab members
Small animal radiotherapy	Chris Johnstone, Nolan Esplen
X-ray imaging with photon-counting detectors	Pierre-Antoine Rodesch, Devon Richtsmeier, Jericho O'Connell
FLASH/spatially-fractionated radiotherapy	Nolan Esplen, Alex Hart, Jon Eby
Low-cost kilovoltage arc therapy	Jericho O'Connell, Dylan Breitkreutz

Small animal radiotherapy

We are interested in improvements of dose delivery accuracy performed with image-guided small animal irradiators, such as with the small animal radiation research platform (SARRP) by Xstrahl, Inc and the small animal radiotherapy (SmART) system by PXi. To this end, we have performed a multi-institutional study on the image quality and guidance of the two systems. In collaboration with Oxford and Xstrahl, we have developed and evaluated a 3D-printed phantom for small animal image quality and targeting assessment. Left: Photograph (a) and schematic drawing (b) of the small animal imaging and targeting phantom designed with Oxford and Xstrahl. Right: MicroCT images of the various phantom sections acquired in the pancake imaging geometry on the SARRP

Left: Photograph (a) and schematic drawing (b) of the small animal imaging and targeting phantom designed with Oxford and Xstrahl. Right: MicroCT images of the various phantom sections acquired in the pancake imaging geometry on the SARRP

We have also designed a 3D-printed phantom for evaluation of dosimetry. This phantom was built based on a microCT scan of a mouse with a subcutaneous tumor on its right hind leg. The phantom was 3D printed with two different materials mimicking soft tissue and bone. The bone material was only slightly different than the soft tissue material and provided mainly visual contrast rather than CT contrast. The lungs were excavated and filled with polystyrene to mimic lung tissue. Top: Photograph (a) and 3D-volume rendering of the mouse dosimetry phantom. Bottom: Calculated (left) and measured (right) dose distributions for a 10x10mm 2-beam treatment (a) and 3x3mm arc treatment (c)

Top: Photograph (a) and 3D-volume rendering of the mouse dosimetry phantom. Bottom: Calculated (left) and measured (right) dose distributions for a 10x10mm 2-beam treatment (a) and 3x3mm arc treatment (c)

The phantom was equipped with two different dosimeters to enable dose measurements that was tested with a number of treatment scenarios on the SARRP.The phantom was split into two pieces in order to allow for an insertion of a laser-cut Gafchromic film for measurements of 2D doses. Dose distributions measured by the film agreed well with Monte Carlo calculated doses. Additionally, three holes in the brain, abdomen and in the orthotopic tumors were included in the model for the insertion of a plastic scintillator dosimeter (PSD). Thanks to our collaboration with François Therriault-Proulx of MedScint and Luc Beaulieu of Laval University we were able to evaluate the use of their PSD to small animal radiotherapy. We then used it for dose evaluation in these three sites for various treatment setups and found a good agreement with Monte Carlo simulations.

X-ray imaging with photon-counting detectors

Novel x-ray imaging: experimental setup on our table-top system (a), PCCT images of Gd (top) and Au (bottom) contrast agents (b) and XFCT sinograms and images of the same phantom (c).

We investigate novel x-ray CT imaging modalities for improved cancer diagnosis and treatment by integrating photon-counting detectors into our table-top x-ray imaging system. We have two streams of research in this area: 1) x-ray fluorescence CT (XFCT) and 2) photon-counting CT imaging (PCCT). Both modalities can be used for the visualization of high-atomic number materials attached to agents targeting a specific site or a molecular processes.
XFCT is a promising imaging modality for visualization of high atomic number contrast agents by detecting the x-ray scattered beam using photon-counting detectors with high energy resolution (1-2%). We have performed Monte Carlo simulations of XFCT imaging using a number of different detectors, as well as simulations of XFCT imaging with various excitation beams. We have also experimentally verified our results with Amptek CdTe detectors using a number of contrast agents (I, Gd, Au).
Since October 2018, we have collaborated with Redlen Technologies on photon-counting CT imaging. We currently have a 2.4x0.8 cm pixelated CZT detector that we are testing for PCCT of high-atomic contrast agents, such as gold or lanthanide nanoparticles. Thanks to our collaboration with Prof. van Veggel's group in the UVic Chemistry department, we have been able to evaluate the capability of our CZT detector to image lanthanide contrast agents very close in atomic number.

FLASH/spatially-fractionated radiotherapy

The custom-made microbeam collimator for the delivery of SFRT on the SARRP, surface dose distribution and surface beam profile measured by EBT3 films.

FLASH and spatially-fractionated radiotherapy (SFRT) have shown great promise in the decrease of side-effects while maintaining the potential to kill tumor cells. SFRT has been implemented in the form of microbeams, minibeams of grid therapy, mainly on synchrotron sources with limited access. We are investigating the feasibility to deliver SFRT on the SARRP system. We have built a custom collimator that can be inserted into the SARRP 10x10 mm nozzle and results in peak-to-valley dose ratios (PVDRs) of ~13 and isocenter dose rates of ~ 1.2 Gy/min. We have also tested two other 3D-printed tungsten miniGRID and microGRID collimators for SFRT dose delivery on the SARRP. The microGRID collimator with 400 μm slit size and 287.5 μm center-to-center distance resulted in high PVDR values of 58.
TRIUMF FLASH/MRT setup

We demonstrated that conventional x-ray tubes are capable of FLASH dose delivery and published on this as a Medical Physics Letter. We have built a custom beam shutter to alow for irradiations as short as 1 ms and have used this system to evaluate a number of organic, inorganic and hybrid scintillator dosimeters for ultrahigh dose-rate dosimetry. Currently we are optimizing the shutter system for uniform dose delivery across a 6-mm diameter sample. We started investigating the survival of fruit flies after ultrahigh dose-rate (UHDR) delivery and our preliminary results are promising. The next step will involve irradiations of 3D printed normal and cancerous skin cells.
In addition, we are working on building a FLASH irradiation station at the ARIEL beamline at TRIUMF, a high-energy physics laboratory in Vancouver. By means of heat transport simulations, we have designed an electron-to-photon converter for the delivery of an ultrahigh dose-rate 10 MV photon beam on the existing medium energy beam dump. Our beam modeling 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. Additionally, thanks to Monte Carlo simulations with the TOPAS code, we have designed a GRID collimator for the delivery of SFRT with PVDR of ~5. The aim of the NFRF-E funded project is to investigate the FLASH effect for open and spatially-fractionated beams on healthy lungs of mice with the 10 MV beam. After 2.5 years of designing a target to convert high-flux 10 MeV electrons to 10 MV photons on the TRIUMF ARIEL beamline, we started our FLASH irradiation station installation in October 2021. Hopefully we will soon be able run experiments to investigate the FLASH effect with ultrahigh dose rate high-energy photons.

Low-cost kilovoltage arc therapy (KVAT)

Top: The principle of KVAT dose delivery. Bottom A design of the KVAT machine (left) and KVAT and SABR dose calculations for a lung patient (right)

Access to radiotherapy therapy is limited in low- and middle-income countries (LMIC). In some LMIC <10% of eligible patients have access to radiotherapy due to its high cost.The standard of RT care is the delivery of high‐energy (6–15 MV) photons, generated by a medical linear accelerator (linac), to the site of disease. Linacs utilize a number of expensive technologies, such as precisely machined waveguides and high‐voltage generators, to accelerate electrons to relativistic speeds. Upon collision with a tungsten target these electrons produce megavoltage (MV) bremsstrahlung photons, which are filtered, collimated, and directed to the site of treatment. The high energy of these photons necessitates expensive treatment infrastructure known as "vaults" to house the linac in order to shield medical personnel from radiation. The result of this high cost is strain on healthcare systems.
The goal of this project is to design a low-cost radiotherapy device that uses kilovoltage x-rays. Compared the linac-driven megavoltage x-rays, high beam attenuation and low beam output have to be overcome. So far, we have demonstrated proof of principle by means of Monte Carlo simulations and some limited experiments on phantoms. In collaboration with McGill University, we have developed KVAT treatment planning optimization. We have demonstrated that the most suitable candidates for KVAT treatments might be breast and lung patients, but not prostate patients. Our industrial partner Precision RT (Las Vegas, NV) is currently testing the first machine prototype and we are assisting with the experimental validation.