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Investigation of low energy, alternative X-ray sources and their interactions with multi-Z materials for theranostics

Westphal, Maximillian

Abstract Details

2019, Doctor of Philosophy, Ohio State University, Biophysics.
A computational and theoretical investigation into alternative X-ray sources and their interactions with heavy element materials for improving radiation therapy and diagnostics (theranostics) is reported. About half of patients being treated for cancer undergo radiation therapy with high energy X-rays produced by linear accelerators (LINAC). These X-rays are produced on a broadband X-ray spectrum (BX), so a majority of these X-rays are not useful in therapy. The lowest energy X-rays (< 30 keV) are unable to penetrate far into the body as they are absorbed by the skin and healthy tissue leading up to the targeted tumor. The high energy X-rays are able to penetrate deeply into the body but show very little interaction with lighter molecules and elements common in tissue (water, oxygen, and even calcium). To compensate for the energy inefficiencies of high-energy therapeutic X-rays, we investigate alternative methods of generating X-rays. Synchrotron-produced monochromatic, single-energy X-rays (MX) avoid the energy inefficiency of BX; however, they are impractical for biomedical applications due to synchrotrons' large size (1 km diameter), cost, and high intensities. Quasi-monochromatic X-rays (QX) fall between BX and MX: they are selective in energy but have a low background. Many QX sources use existing technology, such as high intensity lasers (HIL) to generate tunable QX while others use heavy element plates to filter out the unwanted high and low energy photons. One source using this filtering technique is studied in depth in this document using a combination of experimental, computational, and theoretical techniques. This source was created using a 150 kV imaging device in combination with a zirconium (Zr) plate to convert its BX spectrum into a high flux of Zr K-alpha, a process we call broadband-to-monochromatic (B2M) conversion. We report that these QX and MX sources can achieve similar contrast to conventional BX sources when used for imaging and that inverse Compton scattering sources deposit less radiation into the phantom while doing so. It has been shown that tumors embedded with heavy element nanomoieties such as gold (Au) nanoparticles (NPs) or platinum-based (Pt) chemotherapy drugs enhance radiation dose deposition. When nanomoieties are used in combination with kV sources, such as those used in imaging, the amount of radiation deposited into a tumor can be an order of magnitude higher than conventional high energy LINAC methods can achieve. To investigate these new alternative X-ray sources in combination with heavy element nanomoieties, we employ Monte Carlo simulations using Geant4, calculations using SUPERSTRUCTURE, radiative transfer modeling, and experimental techniques. Monte Carlo simulations allow great flexibility in building phantom models of the body as well as testing any X-ray source imaginable. SUPERSTRUCTURE calculations inform the inputs of the simulations to better choose MX and QX energies to target atomic processes. Radiative transfer modeling provides a comparison for the simulations to ensure accuracy, and experiments show the practical limitations of the methods we test computationally. We report that NP-induced dose enhancement can be achieved while sparing intervening healthy tissue by using low-energy MX or QX sources that target characteristic energies of heavy element nanomoieties, such as the K-alpha or K-edge energies, to ionize their electrons and trigger Auger cascades. Using Monte Carlo techniques, we show that these emitted electrons make up a portion of the dose enhancement and can achieve strand breaks in DNA, potentially leading to cell-death. The data show that inverse Compton scattering sources in combination with a mixture of gold and gadolinium NPs results in the greatest dose enhancement in tumors while penetrating deep into the body. However, MX sources at gold K-edge energies create a spectrum of Auger electrons that results in more DNA double strand breaks. Finally, it is theorized that combinations of MX beams tuned to the K-edge and K-alpha of atoms can trigger an increase in ejected ionized and Auger electrons as well as K-alpha photons in targeted NPs, a process named pumping K-alpha resonance fluorescence. We investigated this process using simulations of MX beams and inverse Compton scattering sources targeting gold, gadolinium, platinum, and bismuth NPs' K-edge and K-alpha energies. While some dose enhancement was seen using the twin beam setup, it was comparable to MX sources alone when using base Geant4 physics lists. Our findings here contribute further to understanding the interactions between new X-ray sources and heavy element nanomoieties. This work provides new insights into QX sources currently in development and shows what may be achieved should those sources be further optimized, particularly in the case of inverse Compton scattering sources. In addition, we have shown that mixtures of gold and gadolinium NPs may provide larger radiation dose enhancements when used in combination with these new alternative X-ray sources.
Anil Pradhan (Advisor)
Sultana Nahar (Committee Member)
Enam Chowdhury (Committee Member)
Ronald Xu (Committee Member)
227 p.

Recommended Citations

Citations

  • Westphal, M. (2019). Investigation of low energy, alternative X-ray sources and their interactions with multi-Z materials for theranostics [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1571133365330023

    APA Style (7th edition)

  • Westphal, Maximillian. Investigation of low energy, alternative X-ray sources and their interactions with multi-Z materials for theranostics. 2019. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1571133365330023.

    MLA Style (8th edition)

  • Westphal, Maximillian. "Investigation of low energy, alternative X-ray sources and their interactions with multi-Z materials for theranostics." Doctoral dissertation, Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1571133365330023

    Chicago Manual of Style (17th edition)