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Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and in Vivo

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Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and in Vivo 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 12-2016 Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo Christopher M. Walker Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons, and the Other Physics Commons Recommended Citation Walker, Christopher M., "Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo" (2016). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 712. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/712 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]. Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo by Christopher Michael Walker APPROVED: ________________________________________________________ James A. Bankson, Ph.D. (Advisory Professor) ________________________________________________________ John Hazle Ph.D. ________________________________________________________ Dawid Schellingerhout M.D. ________________________________________________________ Richard Wendt Ph.D. ________________________________________________________ Steven Millward Ph.D. ________________________________________________________ Arvind Rao Ph. D. APPROVED: ________________________________________________________ Dean, The University of Texas Graduate School of Biomedical Sciences at Houston NOVEL SIMULATION TO AVOID BIAS IN MEASUREMENT OF HYPERPOLARIZED PYRUVATE: DEMONSTRATED IN PHANTOM AND IN VIVO A DISSERTATION Presented to the Faculty of The University of Texas Health Science Center at Houston And The University of Texas M.D. Anderson Cancer Center Graduate School of Biomedical Sciences in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY by Christopher M. Walker B.Sc. Trinity University, 2010 Houston, Texas December 2016 iii Copyright iv Dedication To my mother and father, Cheryl and Mike Walker, and my sister, Ashley Walker, for their ceaseless support and encouragement. v Acknowledgment I would like to thank my adviser, Dr. James A. Bankson, for his patience and dedication to my development as an academician. Under his tutelage I have grown tremendously in the way I think about problems and how I present my thoughts, especially using the written word. No one would have predicted that the dyslexic 4th grader would one day write a dissertation, and my thanks to Dr. Bankson is paramount in the achievement of that goal. I would also like to thank my committee members for their time and dedication to my project and my development throughout all stages of my post-graduate education. Dr. Hazle, who first encouraged me to continue to explore magnetic resonance imaging as a summer student who could barely wrap his head around frequency encoding gradients. I would not be here today if not for his initial support which, much to my benefit, has followed me throughout my graduate training. Dr. Wendt, to whom I owe the bulk of my understanding of the phenomenon of magnetic resonance, thanks to his unflagging didactic efforts. If Haacke is the magnetic resonance bible, then Dr. Wendt’s tie lecture is the MRI sermon on the mount. Statistical analysis is fraught with pitfalls and I have my many meetings with Dr. Rao to thank that this project never found itself hopelessly lost in a statistical quagmire. The extent to which I understand biochemical processes an enzyme kinetics is owed to the instruction of Dr. Milward. Finally, Dr. Schellingerhout, if I am able to achieve any semblance of the enthusiasm you possess for investigative pursuits, while maintaining your grasp of the difficulty inherent in them, I will be truly blessed as an academician. I have been fortunate to be involved in the Julia Jones Matthews and M.D. Anderson CPRIT scholar program for four years. Not only has this program supported my work and allowed me to present said work at multiple meetings, it has also given me exposure to aspects of cancer biology I simply would not have seen outside of the program. Dr. Watowich, thank you for all your help and effort with the CPRIT program. I hope I am far from the last student to glean such tremendous benefit from it. vi I would also like to thank all of those who stewarded me into post-graduate academic pursuits. The faculty at Trinity University began the extensive molding necessary for me to succeed after graduation. I especially thank Dr. Hough and Dr. Ugolini who opened my research career and taught me the foundational understanding of physics I needed to be able to approach the phenomenon of magnetic resonance. To Dr. Lewis, I am ever indebted. To whatever extent I possess the ability to write good software I owe it to him, and it has paid dividends in this project and my life as a whole. vii NOVEL SIMULATION TO AVOID BIAS IN MEASUREMENT OF HYPERPOLARIZED PYRUVATE: DEMONSTRATED IN PHANTOM AND IN VIVO Christopher M. Walker B.Sc Advisory Professor: James A. Bankson, Ph.D Abstract Dynamic nuclear polarization creates a transient hyperpolarized nuclear state that can dramatically increase the signal detected by magnetic resonance imaging. This signal increase allows real-time spectroscopic imaging of specific metabolites in vivo by magnetic resonance. Real-time imaging of both the spatial and chemical fate of hyperpolarized metabolites is showing great promise to meaningfully benefit clinical care of cancer patients. Imaging of hyperpolarized agents will have a larger clinical impact if it can function as a quantitative modality upon which clinical decisions can be made. However, quantitative measurement of hyperpolarized agents is currently difficult due to the restrictions imposed by the transient hyperpolarized state and the complexity inherent in biological systems. As more advanced imaging and measurement techniques are developed for imaging hyperpolarized substrates, it is critical to characterize their effect on any relevant quantitative measure. To assist in accurate quantitative measurement of hyperpolarized agents, an infrastructure where acquisition strategies can be developed, compared, optimized and validated was critically need. A novel simulation architecture was developed that combines classical chemical kinetics with the basic physics of nuclear magnetic resonance and couples them to multiple perfusion models. Simulation results showed that changes in the acquisition strategy used will affect the resulting quantification of chemical exchange rates and suggested that any bias that is imposed by the acquisition strategy can be avoided by using optimized pulse sequences. To validate these predictions, a phantom system was developed that allows controllable chemical conversion of hyperpolarized pyruvate into lactate with a variability less than 20%. Using this phantom system, studies showed that poorly optimized pulse sequences viii significantly reduced the measured value of the chemical exchange rates, whereas optimized pulse sequences showed no significant difference in chemical exchange measurements. In order to test simulation predictions for a perfused system, an animal cohort with orthotropic anaplastic thyroid cancer was scanned with multiple sequences. Again, optimized sequences showed no significant difference in measured exchange rates while poorly designed sequences significantly underestimated the exchange rates, which is consistent with the simulation results. These validation studies suggest that this simulation architecture will be a powerful tool for developing and optimizing acquisition and quantization methods for hyperpolarized magnetic resonance imaging. ix Table of Contents Acknowledgment .......................................................................................................................................... v Abstract ....................................................................................................................................................... vii Table of Contents ......................................................................................................................................... ix List of Figures .............................................................................................................................................. xiv List of Tables .............................................................................................................................................. xvii List of Abbreviations ................................................................................................................................. xviii Chapter 1. Introduction and Motivation ......................................................................................................
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