DESKTOP GENERATED MICROPLANAR X-RAY BEAMS AND THEIR BIOLOGICAL EFFECTS Public Deposited

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Last Modified
  • March 21, 2019
Creator
  • Bazyar, Soha
    • Affiliation: School of Medicine, UNC/NCSU Joint Department of Biomedical Engineering
Abstract
  • Cancer affects 1 in 2 men and 1 in 3 women in the US and about half of all cancer patients receive some type of radiation therapy sometime during the course of their treatment. Normal tissue toxicity is the most important dose-limiting side effect of radiotherapy. This effect not only occurs after conventional broad beam radiotherapy (BB) but also following new radiation modalities namely, intensity modulated radiotherapy and proton therapy. Microbeam radiotherapy (MRT) is a novel preclinical approach for radiotherapy, which delivers spatially fractionated submillimeter lines of the collimated quasi-parallel of a single high-dose (100Gy<) radiation (peaks), separated by wider nonirradiated regions (valleys). Interestingly, the preclinical studies on animal models have consistently demonstrated the selective tumoricidal effect of MRT with the ability to even cure the aggressive orthotropic tumor models while sparing the normal tissue. Most of the MRT studies have been conducted in spars synchrotron facilities around the world. To make this technology more available for preclinical biomedical studies and facilitate the translation of this promising modality to the clinic, here a desktop approach for applying MRT has been sought. My dissertation goal was to develop a more accessible microbeam approach, study its effectiveness and evaluate some of the hypothetical underlying radiobiological mechanism of the desktop MRT approach. In this work, first, the effect of MRT and BB on normal mouse brain will be evaluated using batteries of neurocognitive tests, up to 8-months post irradiation. Next, a novel method for applying microbeams using an industrial cabinet animal irradiator will be introduced and a detailed description of its final characteristics will be given, including a comprehensive evaluation of the treatment geometry and a full-scale phantom-based quantification of its dosimetric output. Subsequently, the in-vitro and in-vivo efficacy of this new approach will be investigated. Later, the role of the acquired immune system will be evaluated in the tumor response after MRT. Finally, future project directions will be described briefly. Based on the results of this work, the author’s belief that our approach for applying MRT can be easily reproduced in other research facilities for radiobiological research and has definite clinical translation potential.
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Advisor
  • Su, Maureen
  • Lee, Yueh
  • Tepper, Joel
  • Lalush, David
  • Zhou, Otto
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2018
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