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Use of Positron Emission Tomography for Proton Therapy Verification The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 5-2014 USE OF POSITRON EMISSION TOMOGRAPHY FOR PROTON THERAPY VERIFICATION Jongmin Cho Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Nuclear Commons, and the Radiology Commons Recommended Citation Cho, Jongmin, "USE OF POSITRON EMISSION TOMOGRAPHY FOR PROTON THERAPY VERIFICATION" (2014). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 435. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/435 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. USE OF POSITRON EMISSION TOMOGRAPHY FOR PROTON THERAPY VERIFICATION by Jongmin Cho, B.E., M.S. APPROVED: _____________________________________ Supervisory Professor, Geoffrey Ibbott, Ph.D _____________________________________ Osama Mawlawi, Ph.D _____________________________________ Michael Gillin, Ph.D _____________________________________ Carlos Gonzalez-Lepera, Ph.D _____________________________________ Francesco Stingo, Ph.D _____________________________________ Harald Paganetti, Ph.D APPROVED: __________ __________________ Dean, The University of Texas Graduate School of Biomedical Sciences at Houston USE OF POSITRON EMISSION TOMOGRAPHY FOR PROTON THERAPY VERIFICATION A DISSERTATION Presented to the Faculty of The University of Texas Health Science Center at Houston and The University of Texas MD Anderson Cancer Center Graduate School of Biomedical Sciences in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY by Jongmin Cho, B.E., M.S. HOUSTON, TEXAS May, 2014 © Copyright by Jongmin Cho 2014 All Rights Reserved iv DEDICATION I dedicate my dissertation work to my wife Rachel whose love and support lifted me from start to finish; my mother, Soonin who always sacrificed herself for the well-being of her children; my father, Youngbae whose perseverance and quest for knowledge inspired me, and to my three elder sisters, Jungim, Jungsun, and Hyunjoo who always looked after their younger brother. My sincerest dedication goes to those suffering from cancer and those who suffer alongside them. This work is especially dedicated to God the Father, God the Son, and God the Holy Spirit Who provided me research ideas, strength to continue, and surrounding me with wonderful people who made my research possible. “The Lord is my light and my salvation; whom shall I fear? The Lord is the strength of my life; of whom shall I be afraid?” – Psalm 27:1 v ACKNOWLEDGEMENTS First and foremost, I wish to express my heartfelt gratitude to my mentors, Drs. Geoffrey Ibbott and Osama Mawlawi who generously supported me financially and provided me ample amount of time and opportunities. Although this dissertation is an important fruit of great relationships with both mentors, they taught and sow something as important – great leadership and mentorship which I may bear fruit after graduation. I would like to acknowledge and thank my former research mentor, Dr. Reinhard Schulte at Loma Linda University for his unfailing support that spanned almost a decade. I would also like to thank Dr. Pablo Yepes from Rice University and Dr. Uwe Titt for their great support with the Monte Carlo simulation. Thank you to Dr. Michael Gillin, Richard Amos and Matthew Kerr for their expertise of proton measurements. Thank you to Drs. Carlos Gonzalez-Lepera and Francesco Stingo for their advice and help with their expertise which was essential for this dissertation. Many thanks to the departments of Radiation Oncology and Radiology at Massachusetts General Hospital, with a special thanks to Drs. Harald Paganetti and ChulHee Min who have been pivotal in the collaborations between Massachusetts General Hospital and MD Anderson Cancer Center. Last, but not least, I would like to thankfully acknowledge my colleagues, staff and faculty members - Dr. Pan, Dr. Wendt, Dr. Sahoo, Moiz, Kevin Casey, Kevin Vredevoogd, Mitchell, Ryan, Lawrence, Paige, Paul Wisdom, Frances, Bryan Steward, Justin, Rachael, Majid, Shuaiping and many others who played an integral part in my dissertation. vi USE OF POSITRON EMISSION TOMOGRAPHY FOR PROTON THERAPY VERIFICATION Jongmin Cho, B.E., M.S. Supervisory Professor: Geoffrey Ibbott, Ph.D. Positron emission tomography (PET), a tool commonly used for cancer staging and response monitoring, has recently been used for proton therapy verification. By imaging tissue activation following proton treatment, attempts have been made to verify proton dose and range . In this dissertation, two novel approaches were developed and tested for the purpose of help improve the proton dose and range estimation as well as verification. Although there are still some challenges, attempts for proton dose verification using PET has been made by comparing Monte Carlo dose and PET simulations with treatment planned dose and measured PET. In this approach, generic tissue composition information is used which can cause large uncertainties in Monte Carlo PET simulation. To improve these uncertainties, we developed a method in the first part of the research to obtain tissue elemental composition using PET after proton therapy. Proton activation of tissue creates progeny radioisotopes according to constituting tissue elements’ cross sections and proton energies. The time-activity-curves from activated tissues can be separated into constituting progeny radioisotopes using a least squares method and then to constituting elemental compositions using Monte Carlo simulated proton energy and cross-section information. We tested this approach using a phantom consisting of sections composed of different combinations of 12 C and 16 O irradiated using a mono-energetic and a SOBP proton beam. In vii addition, two patient studies were also evaluated using the same technique immediately after proton treatments. The 12 C and 16 O compositions were estimated within 3.6% accuracy in the phantom studies and within 15.2% for patient studies. The obtained tissue elemental composition can be used to improve proton dose verification using PET. In the second part of this dissertation, we developed a new approach to verify proton range. Conventional proton range verification is performed by correlating the distal end of measured PET signals to the proton range. However, this approach is affected by minimal tissue activation near the end of the proton range, perfusion-driven activity washout, and short half-lives of progeny radioisotopes. This also requires an in-beam, in-room, or on-site PET scanner which can be financially and technically challenging for many proton centers. Our new approach overcomes all of these limitations by using proton activated markers. When implanted near the proton distal end, those markers are strongly activated while tissues are minimally activated. For this work we tested 18 O enriched water, Cu and 68 Zn enriched markers that were embedded in tissue-equivalent materials and imaged using an off-site PET scanner following proton activation. The marker materials provided significantly stronger PET signals near the distal end which can be used to verify proton range. In addition, optimal volumes of those markers were also investigated when imbedded in tissue-equivalent materials while using clinical treatment and imaging scenarios. Our results suggest that marker volumes ranging between 5 and 50 mm 3 are required to provide adequate PET signals. The proposed approach can potentially replace conventional fiducial markers with the added benefit of proton range verification. Two proposed methods performed in this research can be used potentially improve both proton dose verification using PET and proton range verification using an off-site PET. viii Contents __________________________________________________________________________ Dedication ………………………………………………………………………..……... V Acknowledgements ……………………………………………………………………. VI Abstract …………………………………………………………………………........ VII Contents ……………………………………….………………………………………. IX List of Figures …………………………………………………………………………. XI List of Tables ………………………………………………………………………… XVI List of Abbreviations ………………………………………………………........... XVIII 1 Introduction …………………………………………………………………………. 1 1.1 Hypothesis …………………………………………………………………… 2 1.2 Specific Aims ……………………………………………………………….... 3 1.3 Dissertation Organization ……………………………………………………. 4 2 Background …………………………………………………………………………. 6 2.1 Proton Therapy ………………………………………………………………. 6 2.2 Proton Therapy Verifications ……………………………………………....... 9 3 Determination of Elemental Tissue Composition following Proton Treatment using Positron Emission Tomography ………………………………………………….. 13 3.1 Introduction …………………………………………………………………. 13 3.2 Materials and Methods ……………………………………………………... 15 3.2.1 Phantom Activation and PET Imaging …………………………. 15 3.2.2 Method of Decoupling Decay Curves
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