Seminar: Applications of ultrasound in enhancing radiation therapy in in vitro models

Student: Matthew Micsa

Supervisors: Dr. Jahan Tavakkoli and Dr. Raffi Karshafian

Abstract

Ultrasound has been shown to be a very effective tool in cancer therapy where it targets endothelial cells and the destruction of vasculature which leads to tumour cell death. Microbubbles can be stimulated by ultrasound waves which causes them to oscillate, expand and then collapse, resulting in physical and mechanical changes in the surrounding biological environment. These bubbles can be used in cancer therapy either as carriers for targeted drug delivery or in combination with radiation therapy. Novel demonstrations of ultrasound-stimulated microbubbles have been recorded as a new anti-cancer therapy when used alone, with chemotherapy, or in combination with radiation therapy. There is also an increase in the probability of sparing normal tissues during treatment when compared to using anti-angiogenic drugs, attributed to both blood vessel destruction and tumour tissue damage.

This project will investigate the effect of ultrasound exposure on biological cells in combination with ionizing radiation on cell viability and DNA damage. Theoretical/mathematical modelling of cell-survival analysis (e.g., linear-quadratic model) will be performed to incorporate the effect of ultrasound into the model (e.g., alpha and beta parameters). In the first study of this project, clonogenic assays will be performed on MDA-MB-231 breast cancer cell cultures following exposures to X-rays, ultrasound, or a combination of both. A LIPUS (low-intensity pulsed ultrasound) device will be used to expose cancer cells to ultrasound, and a CellRad+ system will be used to irradiate the cells with X-rays. A linear-quadratic model will then be created to determine the alpha and beta parameters for the survival of normal cells versus tumour cells based on single-dose delivery and ultrasound acoustic pressure.