Improving the Utility of Cherenkov Imaging in the Radiotherapy Clinic
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IMPROVING THE UTILITY OF CHERENKOV IMAGING IN THE RADIOTHERAPY CLINIC A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy by JACQUELINE MARIE ANDREOZZI Thayer School of Engineering Dartmouth College Hanover, New Hampshire May 2018 Examining Committee: Chairman_______________________ Brian Pogue, Ph.D. Member________________________ David Gladstone, Sc.D. Member________________________ Shudong Jiang, Ph.D. Member________________________ Lesley Jarvis, M.D., Ph.D. Member________________________ Olga Green, Ph.D. ___________________ F. Jon Kull, Ph.D. Dean of Graduate and Advanced Studies Abstract More than half of all cancer patients in the United States undergo fractionated, daily radiation therapy as a component of treatment. While radiotherapy is widely regarded as life-saving, errors during delivery can be severe or even fatal, despite their rarity. These incidents may not be noticed immediately, because the treatment beam is not observed directly, and radiation-induced injuries take time to manifest by nature. It is in this context that the goal of the research presented here is to develop new Cherenkov imaging techniques to be used during radiotherapy for quality assurance testing, as well as patient treatment verification. Cherenkov imaging allows for direct optical visualization of radiation dose deposition as ionizing beams pass through dielectric material via the Cherenkov Effect, by which fast-moving charged particles excite optical emission from media as they relax after rapid polarization. The number of Cherenkov photons produced is proportional to radiation dose delivered for a monoenergetic beam. However, the number of photons that can be detected is governed by efficiency in reaching the detector, which is influenced by variation in tissue optical properties in living subjects. This thesis first focuses on clinical patient imaging requirements, and techniques to improve the correlation between detected Cherenkov light intensity and metrics relating to delivered dose. Patients undergoing whole-breast radiotherapy (WBI), volumetric modulated arc therapy (VMAT), and total skin electron therapy (TSET) are discussed. Quality assurance imaging is more straightforward, since the optical properties of the irradiated subject can be controlled. The remainder of this thesis employs water tanks ii and solid plastics to measure relative dose optically. These methods are adapted to accommodate atypical large field setups for TSET, as well as cutting edge clinical systems combining concurrent magnetic resonance imaging with radiotherapy delivery systems (cobalt-60 and linac based). iii Acknowledgements Navigating the pursuit of a Doctor of Philosophy degree takes a considerable amount of support, guidance, and encouragement. I have been fortunate to have an excess of all of these over the years, from my advisors, research collaborators, friends and family. I would like to thank all of the wonderful people that I have met, worked with, and learned from during my time at Dartmouth College, but in particular, the following individuals: . Dr. David Gladstone, for constantly inspiring my research with your undeniable aptitude and fascination with medical physics (and intellectual pursuits in general). Dr. Lesley Jarvis, for helping me understand that at the end of the day, the reason we are all here is to help our patients, through both science and compassion. Dr. Shudong Jiang, for continuously offering me new insight and ways to think about the principles governing the optical physics backbone of my research. Dr. Olga Green, for sharing your admirable expertise, and always being willing and excited to collaborate on experiments. Dr. Benjamin Williams and Dr. Colleen Fox, for always being there to answer my questions, and teaching me what it means to be a clinical medical physicist. Dr. Rongxiao Zhang and Dr. Adam Glaser, for showing me how to be a successful graduate student (and beyond). iv . Dr. Petr Bruza, for bringing your new ideas and technical capabilities to the research group, and always providing insightful direction to the research. Dr. Karen Mooney, for seeking me out that one fateful day at the AAPM 2015 Annual Meeting; our conversation turned into a collaboration fundamental to my thesis. My fellow graduate students at Thayer School of Engineering, who have come and gone over the years as they reached their milestones of success; we learned from each other how to navigate the world and experience of graduate school. And last, but perhaps most notably: . Dr. Brian Pogue, for instilling in me the importance of being a researcher contributing to the scientific community, for your patience and understanding as I learned and grew in my capacity as both a scientist and a person, and for always having your door (and inbox) open to provide guidance and reassurance. You taught me how to write papers, how to present at conferences, and how to do good, meaningful science. I will always be grateful for your mentorship, and would not be where I am today without it. I would finally like to thank the family, who have endured this experience by proxy, and continue to give me to the drive to succeed as my career progresses. My parents, siblings, and in-laws have all done this from afar, offering constant encouragement and support when I need it the most. My wonderful husband, Ryan, and our young son Edwin, give me purpose and inspiration each and every day, and I would be lost without them. v Table of Contents Abstract................................................................................................................................ii Acknowledgements ............................................................................................................ iv Table of Contents ............................................................................................................... vi List of Figures ...................................................................................................................... xi List of Tables ..................................................................................................................... xix List of Acronyms ................................................................................................................ xx Chapter 1: Introduction .................................................................................................... 21 1.1 Problem Statement ................................................................................................ 21 1.2 Approach to Solving the Problem .......................................................................... 22 Chapter 2: Background ..................................................................................................... 24 2.1 Cherenkov Emission Physics .................................................................................. 24 2.1.1 Cherenkov Emission Spectra ............................................................................ 28 2.1.2 Simulating Cherenkov Emission ....................................................................... 30 2.1.3 Detection Approaches ...................................................................................... 31 2.2 The Radiotherapy Clinic ......................................................................................... 34 2.2.1 Whole Breast Irradiation .................................................................................. 38 2.2.2 Mycosis Fungoides and Total Skin Electron Therapy ....................................... 39 2.2.3 Magnetic Resonance Imaging Guided Radiotherapy ...................................... 41 2.2.4 Volumetric Modulated Arc Therapy ................................................................. 43 2.2.5 Cherenkov Imaging During Proton Therapy .................................................... 44 2.3 Quality Assurance with Cherenkov Imaging ......................................................... 45 2.3.1 Static Beam Analysis in 2D ............................................................................... 46 2.3.2 Optical Cone-Beam Tomographic Reconstruction ........................................... 47 2.3.3 Real-Time Dynamic Plan Visualization ............................................................. 48 2.4 Review of Other Medical Cherenkov Detection Applications .............................. 49 2.4.1 Nuclear Medicine ............................................................................................. 49 2.4.2 Molecular Imaging and Assays ........................................................................ 53 Chapter 3: Cherenkov Emission Detector Selection Study ............................................. 54 3.1 Cameras .................................................................................................................. 55 3.2 Experimental Setup ................................................................................................ 60 3.3 Image Acquisition and Processing ......................................................................... 61 vi 3.4 Metric of Performance ........................................................................................... 67 3.5 Standalone Detector Results ................................................................................. 68 3.6 Intensified Detector Results .................................................................................. 69 3.7 Camera Selection Discussion ................................................................................