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Applications of Cherenkov Light Emission for Dosimetry in Radiation Therapy a Thesis Submitted to the Faculty in Partial Fulfill

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Applications of Cherenkov Light Emission for Dosimetry in Radiation Therapy a Thesis Submitted to the Faculty in Partial Fulfill Applications of Cherenkov Light Emission for Dosimetry in Radiation Therapy A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy by Adam Kenneth Glaser Thayer School of Engineering Dartmouth College Hanover, New Hampshire May 2015 Examining Committee: Chairman_______________________ Brian Pogue, Ph.D. Member________________________ Alexander Hartov, Ph.D. Member________________________ Eric Fossum, Ph.D. Member________________________ David Gladstone, Sc.D. Member________________________ Lei Xing, Ph.D. ___________________ F. Jon Kull Dean of Graduate Studies THIS PAGE IS INTENTIONALLY LEFT BLANK, UNCOUNTED AND UNNUMBERED ADDITIONAL ORIGINAL SIGNED COPIES OF THE PREVIOUS SIGNATURE PAGE ARE RECOMMENDED, JUST IN CASE. Abstract Since its discovery during the 1930's, the Cherenkov effect has been paramount in the development of high-energy physics research. It results in light emission from charged particles traveling faster than the local speed of light in a dielectric medium. The ability of this emitted light to describe a charged particle’s trajectory, energy, velocity, and mass has allowed scientists to study subatomic particles, detect neutrinos, and explore the properties of interstellar matter. However, only recently has the phenomenon been considered in the practical context of medical physics and radiation therapy dosimetry, where Cherenkov light is induced by clinical x-ray photon, electron, and proton beams. To investigate the relationship between this phenomenon and dose deposition, a Monte Carlo plug-in was developed within the Geant4 architecture for medically-oriented simulations (GAMOS) to simulate radiation-induced optical emission in biological media. Using this simulation framework, it was determined that Cherenkov light emission may be well suited for radiation dosimetry of clinically used x-ray photon beams. To advance this application, several novel techniques were implemented to realize the maximum potential of the signal, such as time-gating for maximizing the signal to noise ratio (SNR) and Cherenkov-excited fluorescence for generating isotropic light release in water. Proof of concept experiments were conducted in water tanks to demonstrate the feasibility of the proposed method for two-dimensional (2D) projection imaging, three-dimensional (3D) parallel beam tomography, large field of view 3D cone beam tomography, and video-rate dynamic imaging of treatment plans for a number of common radiotherapy applications. The proposed dosimetry method was found to have a number of unique advantages, including but not limited to its non-invasive nature, water-equivalence, speed, high-resolution, ability to provide full 3D data, and potential to yield data in-vivo. Based on these preliminary results, it is expected that Cherenkov light emission may prove to be a useful tool for radiation dosimetry with both research and clinical applications. ii Preface First and foremost I would like to thank my advisor, Brian Pogue, for his mentorship and support throughout the course of my entire time at Dartmouth College. When I began my journey towards a Ph.D., I asked my undergraduate advisor if she could recommend any researchers in the field of biomedical optics in the New England area. Of the names she listed, Brian was at the top of her list, and I distinctly remember her telling me I could not find a better researcher and kinder person to study under. Looking back on my graduate experience, she could not have been more right – and for this, I am very thankful. I would also like to thank my family for instilling in me an intellectual curiosity, and for ultimately motivating me to pursue a graduate degree. iii Table of Contents Abstract ii Preface iii Table of Contents iv List of Tables viii List of Figures ix List of Acronyms xviii Introduction 1 1.1 Radiation Therapy 1 1.1.1 The Medical Linear Accelerator 2 1.1.2 Dose 3 1.1.3 Dose Profiles 5 1.2 Quality Assurance 6 1.2.1 Commissioning 8 1.3 Photon Interactions in Matter 12 1.3.1 The Photoelectric Effect 13 1.3.2 Compton Scattering 13 1.3.3 Pair Production 15 1.3.4 Rayleigh Scattering 15 1.3.5 Total Mass Attenuation Coefficient 16 1.4 Charged Particle Interactions in Matter 16 1.4.1 Soft Collisions 17 1.4.2 Hard Collisions 18 1.4.3 Coulomb Force Interactions 19 1.4.4 Total Mass Stopping Power 19 Radiation-induced Light Emission 23 2.1 The Cherenkov Effect 23 2.1.1 Physical Origin 24 2.1.2 Characteristics 25 2.1.3 Relevance to Radiation Therapy 28 Monte Carlo Simulations of Radiation-induced Light Transport 31 3.1 Tissue Optics Plug-in for GEANT4/GAMOS 35 3.2 Validation Simulations 40 3.3 Example Radiation-induced Optical Simulations 45 iv 3.4 Discussion and Conclusions 53 The Relationship between Cherenkov Light Emission and Dose 61 62 4.1 Analytic Theory 62 4.2 Monte Carlo Simulations 64 4.3 Cherenkov Light Emission Estimation for X-ray Photons 64 4.3.1 Point Kernels 66 67 4.3.2 Pencil Beams 67 4.3.3 Polyenergetic Beams 69 4.3.4 Finite Field Size Beams 71 4.3.5 Multiple Beams 76 4.4 Cherenkov Light Emission Estimation for Electrons 77 4.4.1 Pencil Beams 78 4.4.2 Finite Field Size Beams 80 4.5 Cherenkov Light Emission Estimation for Protons 81 4.5.1 Pencil Beams 83 4.5.2 Finite Field Size Beams 84 4.6 Discussion and Conclusions 85 4.6.1 X-ray Photons 85 4.6.2 Electrons 88 4.6.3 Protons 88 4.6.4 Cherenkov Light Emission Anisotropy 89 Projection Imaging of Photon Beams by the Cherenkov effect 94 5.1 Methods 97 5.1.1 Image Processing 98 5.1.2 Monte Carlo Simulations 99 5.1.3 Calibration Factor Determination 100 5.1.4 Image Calibration 101 5.1.5 Signal to Noise Ratio 102 5.1.6 Measurement Variability 102 5.1.7 Dose Profile Comparison 102 5.1.8 Reference Dose Distribution 103 5.2 Results 103 5.2.1 Monte Carlo Simulations 103 5.2.2 Calibration Factor Determination 106 5.2.3 Signal to Noise Ratio 109 v 5.2.4 Measurement Variability 111 5.2.5 Dose Profile Comparison 111 5.3 Discussion 113 5.4 Conclusions 117 Projection Imaging of Photon Beams Using Cherenkov-excited Fluorescence 123 6.1 Methods 125 6.1.1 Imaging Parameters 127 6.1.2 Fluorophore Selection 128 6.1.3 Fluorescence Experiments 131 6.1.4 Noise Characteristics 132 6.1.5 Noise Linearity 133 6.1.6 Dose Linearity 133 6.1.7 Signal to Noise Ratio 133 6.1.8 Dose Rate Dependence 133 6.1.9 Field Size Dependence 134 6.1.10 Dose Profile Comparison 134 6.1.11 Image Processing 134 6.2 Results 135 6.2.1 Fluorescence Experiments 135 6.2.2 Noise Measurements 138 6.2.3 Dose Linearity and Signal to Noise Ratio 139 6.2.4 Dose Rate Dependence 140 6.2.5 Field Size Dependence 141 6.2.6 Dose Profile Comparison 142 6.3 Discussion 143 6.4 Conclusions 146 Three-dimensional Parallel Beam Cherenkov Tomography 149 7.1 Methods 151 7.2 Results 155 7.3 Discussion 157 7.4 Conclusions 158 Three-dimensional Cone Beam Cherenkov Tomography 162 8.1 Experimental Setup 163 8.2 Tomographic Image Acquisition and Processing 165 8.3 Beam Hardening Correction 166 vi 8.4 FDK Reconstruction 168 8.5 Gamma Index Analysis 168 8.6 1D Analysis 169 8.7 Tomographic Acquisition and Processing Results 170 8.8 Beam Hardening Correction Results 171 8.9 FDK Reconstruction Results 172 8.10 Gamma Index Results 173 8.11 1D Analysis Results 174 8.12 Discussion 177 8.13 Conclusions 179 Video-rate Optical Dosimetry of IMRT and VMAT treatment plans 183 9.1 Theory 184 9.2 Monte Carlo Simulations 186 9.3 Experimental Setup 189 9.4 Accuracy Analysis 192 9.5 Results and Discussion 192 9.6 Conclusions 196 Conclusions and Future Directions 202 Appendix 213 A.1 GAMOS Absorption 213 A.2 GAMOS Rayleigh Scattering 217 A.3 GAMOS Henyey-Greenstein Scattering 228 A.4 GAMOS Modified Henyey-Greenstein Scattering 234 A.5 GAMOS User-defined Scattering 242 A.6 GAMOS Fluorescence 254 A.7 Shell Script Batch Routines 267 A.8 MATLAB GAMOS Material Properties Table Maker 269 vii List of Tables Table 1.1: Examples of misadministration in radiation therapy from the 2000 IAEA 6 report. Table 1.2: Summary of commissioning methods, their advantages, and their 10 disadvantages. Table 1.3: Example daily, monthly, and annual QA procedure based on the AAPM 11 TG-40 report. Table 3.1: Implemented tissue optics plug-in classes. 38 Table 3.2: Validation simulations for matched refractive index boundary condition. 40 Table 3.3: Validation of total diffuse reflectance and transmittance for a mismatched 41 boundary condition. Table 6.1: Fluorphore properties. 131 Table 9.1: Details of the delivered IMRT and VMAT treatment plans. 191 viii List of Figures Fig. 1.1. The worldwide statistics for the number of radiotherapy machines per million people 1 is shown. Although the highest densities are in the United States, Europe, Japan, and Australia, almost all countries around the world utilize radiation therapy to some degree. Fig. 1.2. In (a) the gantry schematic for a high-energy photon beam is shown. In (b) the same 2 gantry head is shown for an electron beam. Fig. 1.3. The depth dose curves for a generic photon, electron, and proton beam are shown 5 respectively. Fig. 1.4. In (a) the dependence of each mechanism on atomic number is shown. In (b) the 12 attenuation coefficient of each mechanism as a function of incident energy is plotted for a generic material.
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