Date of Award

Winter 3-22-2024

Document Type

Thesis (Master's)

Department or Program

Engineering Sciences

First Advisor

P. Jack Hoopes

Abstract

Cancer remains the second leading cause of death in the US, and more than 50% of all cancer patients receive radiation therapy (RT), often in combination with surgery, chemotherapy and/or immunotherapy. However, the fundamental limit on radiotherapy treatment efficacy is normal tissue tolerance. One potential way to overcome this limitation is through ultra-high dose rate radiation (FLASH RT). Compared to conventional radiotherapy (CONV RT), FLASH RT has been shown to be just as damaging to cancerous tissue but far more sparing of healthy tissue.

However, clinical translation of FLASH research has been obstructed by the failure of many labs to reproduce similar FLASH sparing effects. We hypothesize that failure to reproduce the FLASH effect is due to lack of standardization of experimental conditions and lack of robust FLASH and small field dosimetry. We hence worked to develop: 1) an invention that allows accurate, real time quantification of delivered dose, temporal beam structure, and field uniformity for FLASH and conventional radiation therapy, and 2) an improved mouse model that elucidates sources of biological variability in FLASH and CONV RT research.

Using a plastic scintillator, CMOS camera, and custom 3D printed frame, we developed an apparatus that quantifies exit beam dose with high spatial resolution for small animal irradiation. Using sinuscope, plastic scintillators, and custom designed, 3D printed camera mounts and collimating beam cones, we developed a dosimeter platform that characterizes the entrance dose temporally and spatially without disrupting beam fluence. This invention was tested in vivo on large mammal irradiation and has competitive advantages over existing clinical dosimeters for FLASH RT, superficial radiation therapy, and intraoperative radiation therapy.

To develop an accurate and reproducible model of the FLASH effect, we engineered a mouse restraint system that ensures consistent lateral and vertical positioning of the mouse relative to the LINAC beam. After FLASH and CONV irradiation, we quantified mouse weight loss, survival, microbiome composition, and pathological changes in the GI tract. We identified two experimental conditions that vary between most FLASH research studies and are not always reported - anesthesia type and mouse gender. These situations significantly alter mouse radiosensitivity.

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