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Dosimetry and Biological Studies for Microbeam Radiation Therapy at the Canadian Light Source

  • Author / Creator
    Anderson, Danielle L.
  • Microbeam radiation therapy (MRT) is a pre-clinical type of radiation therapy that uses an array of high-dose microbeams to treat solid tumours. An intense, quasi-parallel synchrotron beam is collimated to create microbeams several 10s of μm wide, and separated by 100s of μm. Animal studies over the past two decades have demonstrated that the extreme spatial fractionation employed in MRT leads to an unusual normal tissue sparing, while being effective for tumour palliation, and in some cases, ablation. This work considers both physical and biological questions remaining in MRT, with a focus on preparation for MRT experimentation on the two BioMedical Imaging and Therapy (BMIT) beamlines at the Canadian Light Source (CLS). A variety of techniques and detectors were employed to investigate the geometric and relative dosimetric characteristics of the 05B1-1 and 05ID-2 beamlines as a basis for further dosimetry. The absolute air kerma rate on the 05B1-1 beamline was measured for several beam qualities (monoenergetic and filtered polyenergetic x-ray beams) using a cylindrical, variable-length free-air ionization chamber and Monte Carlo simulations were carried out to determine correction factors. Air kerma rates between 4.5 mGy/s and 5.2 Gy/s were measured. Additionally, reference dosimetry was performed using a cavity ionization chamber by applying a geometric correction based on the non-uniform beam profile and the ion chamber response function in the broad synchrotron x-ray beam. This allowed the determination of peak (at the most intense point in the beam) and mean air kerma rates for several beam qualities, with a range from 1.9 cGy/s to 1.9 Gy/s. The MRT dose distributions delivered by the 05ID-2 beamline were investigated theoretically using the Monte Carlo package PENELOPE. This work demonstrated that the 05ID-2 beamline has the necessary energy characteristics to provide the spatial fractionation and penetration required for MRT experimentation. The dose distributions in cubic head phantoms representing small, medium and large animals were also determined to understand the considerations required for moving from small (e.g., rodent) animal experimentation to larger (e.g., cat and dog) animals. The spatial fractionation of MRT dose distributions will necessitate unconventional methods for treatment plan optimization. To explore this requirement, four dose-volume metrics, the peak-to-valley dose ratio, the peak-to-mean-valley dose ratio, the mean dose and the percentage volume below a threshold dose, were explored with changing microbeam array geometry and phantom size. To investigate the DNA damage response in cell cultures to synchrotron-generated microbeams, the formation of γH2AX foci (a marker of DNA double-strand breaks), rates of foci clearance and apoptosis in cultured normal human fibroblasts and malignant glioma cells were examined on the 05B1-1 beamline. The two cell types demonstrated similar trends in γH2AX foci formation and clearance with dose and time after irradiation. Additionally, despite elevated levels of γH2AX foci at late times (up to 72 hours after irradiation), both cell types showed very low levels of apoptosis. The results also highlighted the importance of understanding the DNA damage response specific to cell type, and the consideration of non-apoptotic responses even at high doses. The research in this thesis establishes a foundation in experimental dosimetry, theoretical dosimetry, and cell culture studies for future MRT research on the BMIT beamlines at the Canadian Light Source.

  • Subjects / Keywords
  • Graduation date
    2015-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3N29PC3H
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Oncology
  • Specialization
    • Medical Physics
  • Supervisor / co-supervisor and their department(s)
    • Siegbahn, E. Albert (Karolinska Institute, Stockholm, Sweden)
    • Warkentin, Brad (Oncology)
    • Fallone, B. Gino (Oncology)
  • Examining committee members and their departments
    • Mirzayans, Razmik (Oncology)
    • Menon, Geetha (Oncology)
    • Chang, X. Sha (Radiation Oncology, University of North Carolina)
    • Fallone, B. Gino (Oncology)
    • Sloboda, Ron (Oncology)
    • Siegbahn, E. Albert (Karolinska Institute, Stockholm, Sweden)
    • Warkentin, Brad (Oncology)
    • Rathee, Satyapal (Oncology)