Development of enabling technologies for ultra-high dose rate and spatially fractionated radiation therapy

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dc.contributor.authorEsplen, Nolan Matthew
dc.contributor.supervisorBazalova-Carter, Magdalena
dc.date.accessioned2023-04-22T00:11:15Z
dc.date.available2023-04-22T00:11:15Z
dc.date.copyright2023en_US
dc.date.issued2023-04-21
dc.degree.departmentDepartment of Physics and Astronomyen_US
dc.degree.levelDoctor of Philosophy Ph.D.en_US
dc.description.abstractDespite the important advances that have been made in radiation therapy (RT) over recent decades, there remains an ongoing demand for treatments which are capable of widening the therapeutic window. This might be achieved, for example, by reducing the normal-tissue toxicity observed following RT with curative intent. Ultra-high dose rate (UHDR) FLASH-RT and spatially-fractionated RT (SFRT) techniques are both promising examples of emerging therapies primed to address this unmet need. Unfortunately, the technological requirements for delivering these new modalities have proven to be exceptionally demanding and a limiter to their adoption in a broader context. Therefore, innovative new strategies are required to bring these techniques into a larger number of research centers around the world and to facilitate greater mechanistic understanding ahead, and in support, of future clinical translation. In this body of work, new technologies have been developed which facilitate the delivery, and improved accessibility, of FLASH-RT and SFRT for radiobiological research. Firstly, a multi-slit collimator design and proof-of-concept demonstrated a cost-effective means of enabling micro-beam SFRT on a commercial small-animal irradiator. Thereafter, the design and validation of an anatomically realistic, 3D-printed mouse phantom for small-animal radiobiology research was conducted. The rodent-morphic phantom provides a useful tool for simulation and dosimetric verification of complex experimental configurations in the absence of treatment planning capabilities and supports improved reliability and accuracy of pre-clinical outcomes data. Lastly, in an effort to facilitate x-ray FLASH radiobiology experiments, two different sources were functionalized for UHDR photon beam production: first, using a commercial 160 kVp X-ray tube and, secondly, through the development of a megavoltage (MV) electron-to-photon converter for a high-powered electron linear accelerator. The MV source represented a world-first 10 MeV UHDR-compatible x-ray irradiation platform which was subsequently characterized for use in a first radiobiological experiment investigating FLASH effects in normal tissue for healthy mice at the clinically-relevant treatment energy of 10 MV.en_US
dc.description.scholarlevelGraduateen_US
dc.identifier.bibliographicCitationEsplen, N., Chergui, L., Johnstone, C.D. and Bazalova-Carter, M. (2018) Monte Carlo optimization of a microbeam collimator design for use on the small animal radiation research platform (SARRP). Phys. Med. Biol., 63(17): 175004.en_US
dc.identifier.bibliographicCitationEsplen, N., Alyaqoub, E. and Bazalova‐Carter, M. (2019), Technical Note: Manufacturing of a realistic mouse phantom for dosimetry of radiobiology experiments. Med. Phys., 46(2): 1030-1036.en_US
dc.identifier.bibliographicCitationEsplen, N., Therriault‐Proulx, F., Beaulieu, L. and Bazalova‐Carter, M. (2019), Preclinical dose verification using a 3D printed mouse phantom for radiobiology experiments. Med. Phys., 46(11): 5294-5303.en_US
dc.identifier.bibliographicCitationBazalova‐Carter, M. and Esplen, N. (2019), On the capabilities of conventional x‐ray tubes to deliver ultra‐high (FLASH) dose rates. Med. Phys., 46(12): 5690-5695.en_US
dc.identifier.bibliographicCitationEsplen, N., Egoriti, L., Paley, B., Planche, T., Hoehr, C., Gottberg, A., Bazalova-Carter, M. (2022) Design optimization of an electron-to-photon conversion target for ultra-high dose rate x-ray (FLASH) experiments at TRIUMF. Phys. Med. Biol., 67(10): 105003en_US
dc.identifier.bibliographicCitationEsplen, N., Mendonca, M. and Bazalova-Carter, M. (2020) Physics and biology of ultrahigh dose-rate (FLASH) radiotherapy: A topical review. Phys. Med. Biol., 65(23): 23TR03en_US
dc.identifier.urihttp://hdl.handle.net/1828/14963
dc.languageEnglisheng
dc.language.isoenen_US
dc.rightsAvailable to the World Wide Weben_US
dc.subjectradiotherapyen_US
dc.subjectradiationen_US
dc.subjectcanceren_US
dc.subjectkilovoltageen_US
dc.subjectmegavoltageen_US
dc.subjectx-raysen_US
dc.subjectphotonsen_US
dc.subjectsmall-animal radiotherapyen_US
dc.subjectnovel treatmentsen_US
dc.subjectdosimetryen_US
dc.subjectsimulationen_US
dc.subjectradiochromic filmen_US
dc.subjecttargetsen_US
dc.subjectMonte Carloen_US
dc.subjectfinite element analysisen_US
dc.subjectcollimatoren_US
dc.subjectspatial fractionationen_US
dc.subjectSFRTen_US
dc.subjectmicrobeamen_US
dc.subjectultra-high dose ratesen_US
dc.subjectUHDRen_US
dc.subjectFLASHen_US
dc.subjectacceleratorsen_US
dc.subjecte-linacen_US
dc.subject3D printingen_US
dc.subjectphantomsen_US
dc.subjectthermomechanicalen_US
dc.titleDevelopment of enabling technologies for ultra-high dose rate and spatially fractionated radiation therapyen_US
dc.typeThesisen_US

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