STUDIES OF MAGNETIC NANOPARTICLE SHAPE AND SIZE EFFECTS ON T2 RELAXATION IN MAGNETIC RESONANCE IMAGING, AND POWER ABSORPTION IN AN ALTERNATING MAGNETIC FIELD A Dissertation submitted to the Faculty of the Graduate School of Arts and Sciences of Georgetown University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Physics By Joseph Nicholas York, M.S. Washington, DC August 15, 2012 Copyright 2012 by Joseph Nicholas York All Rights Reserved ii STUDIES OF MAGNETIC NANOPARTICLE SHAPE AND SIZE EFFECTS ON T2 RELAXATION IN MAGNETIC RESONANCE IMAGING, AND POWER ABSORPTION IN AN ALTERNATING MAGNETIC FIELD Joseph Nicholas York, M.S. Thesis Advisor: Edward Van Keuren, PhD ABSTRACT Magnetic nanoparticles have been shown to influence contrast in magnetic resonance imaging (MRI). The magnetic fields of particles vary depending on the shape of the particle. The effects of ferromagnetic nanoparticles with various shapes and sizes on the transverse relaxation rate of water protons were analyzed using T2-weighted MRI. Oblate particles were shown to have a stronger effect on the transverse relaxivity than smaller spherical or prolate particles. A linear relationship between the transverse relaxivity and the ratio of particle surface area to volume was observed. It indicates decreasing the surface area to volume ratio of magnetic nanoparticles enhances the relaxivity. Magnetic particle hyperthermia is the use of ferromagnetic nanoparticles to heat a cancer tumor to destroy it. This phenomenon is possible because these particles absorb power from an alternating magnetic field. Heating trials were performed on aqueous suspensions of ferromagnetic nanoparticles having various shapes and sizes. The results show power absorption of the samples diminishes over time regardless of particle shape or size, and the initial absorption rates of the samples depend on the sample type and preparation conditions. Power absorption was observed in all particles tested, including prolate and oblate particles with anisotropy fields greater than the strength of the applied alternating field. Additionally, large levels of aggregation were observed in all samples tested indicating particle interactions may affect the ability of the samples to absorb energy from the applied field. iii ACKNOWLEDGEMENTS This dissertation is the result of many years of preparation and dedication, as well as numerous sources of help, guidance, and influence. I could not have accomplished this without the support of many other people. I thank you all, and would especially like to thank the following individuals. Dr. Ed Van Keuren, you are my thesis advisor, but you are much more than that. You are a true friend and a role model. Your continuous support, guidance, and patience (so much patience) has kept me on track to achieving this goal. I cannot thank you enough. I would like to thank Dr. Jim Freericks, Dr. Mak Paranjape, and Dr. Chris Albanese for being members of my committee. Thank you for your insights, guidance, and support. Dr. Freericks, a special thank you for always playing great music (Bob Dylan) across the hallway while I worked in the lab. Many thanks to all of the faculty and staff of the Physics Department of Georgetown University. You all made the graduate student experience enjoyable. Leon Der, thank you for all your technical support with my laboratory experiments. I would also like to thank all of my fellow graduate students. It has been an honor to go this course with you, and to share all of the bad times (studying) and good times (not studying) with you all. Thank you Dr. Olga Rodriguez and Dr. Yi-Chien Lee for your help and support with the magnetic resonance imaging research. You were a terrific help. Last, and certainly not least, are my friends and family. I would like to thank my parents, John and Becky York, for their endless support and encouragement to be whatever I wanted to be, which turned out to be a physicist. Your unwavering commitment to making iv your children the best adults they can be has been a source of admiration for me. My three sisters, Anne, Amanda, and Kate, have been sources of inspiration and many laughs. You all make any project feel like a simple task. Thank you. Erika Luth, you have been by my side for nearly all of my graduate school, and you somehow still like me. I could not imagine the world without you in it, and I thank you for all of your support. I will desperately try to repay the kindness, in turn. v I dedicate this work to the entire York family. vi May God bless and keep you always, May your wishes all come true, May you always do for others And let others do for you. May you build a ladder to the stars And climb on every rung, May you stay forever young. x May you grow up to be righteous, May you grow up to be true, May you always know the truth And see the lights surrounding you. May you alway be courageous, Stand upright and be strong, May you stay forever young. x May your hands always be busy, May your feet always be swift, May you have a strong foundation When the winds of changes shift. May your heart always be joyful, May your song always be sung, May you stay forever young. - Bob Dylan vii Table of Contents 1 Statement of Purpose1 2 Cancer 3 I Magnetic Nanoparticle Shape and Size Effects on T2 Relaxation in Magnetic Reso- nance Imaging8 3 Introduction9 4 Magnetic Resonance Imaging 12 4.1 Historical Overview................................ 12 4.2 Water Proton MRI................................ 14 4.3 Water Proton Magnetic Moment Transverse Relaxation............ 17 4.4 Water Proton Transverse Relaxation Pulse Sequences............. 18 4.5 Particle Effects on Image Contrast ....................... 21 5 Materials and Methods 22 5.1 Particle Preparation ............................... 22 5.1.1 Synthesis of Particle 1 .......................... 24 5.1.2 Synthesis of Particle 3 .......................... 25 5.1.3 Synthesis of Particle 4 .......................... 25 5.2 Sample Preparation................................ 27 viii 5.2.1 Agar Phantoms.............................. 27 5.2.2 Particle Concentrations Suspended in Agar............... 28 5.3 System Setup................................... 31 5.3.1 Machine and Software .......................... 31 5.4 Imaging Sequence................................. 31 5.4.1 Multiple Slice Multiple Echo....................... 31 5.5 Imaging ...................................... 32 5.6 Imaging Analysis................................. 33 6 Results and Discussion 34 6.1 Particle Characterization............................. 34 6.2 Inherent Transverse Relaxation of Agar Gels.................. 35 6.3 Transverse Relaxation of Agar Containing Contrast Agents.......... 41 6.4 Shape and Size Effects on Transverse Relaxivity................ 44 7 Conclusions 48 II Magnetic Nanoparticle Shape and Size Effects on Power Absorption from an Al- ternating Magnetic Field 50 8 Magnetic Particle Hyperthermia 51 9 Historical Overview 56 10 Power Absorption of Ferromagnetic Particles From an Oscillating Applied Field 59 10.1 Theoretical Methods of Calculating The Particle Specific Absorption Rate . 63 10.1.1 Power Absorption and Particle Orientation Calculations From Particle Energy................................... 64 ix 10.1.2 Stoner Wohlfarth Theory......................... 69 10.1.3 Linear Response Theory......................... 71 11 Calorimetric Measurement of SAR 74 12 Materials and Methods 76 12.1 Theoretical Models................................ 76 12.1.1 Particle Rotation in a Viscous Medium................. 76 12.2 Sample Preparations ............................... 77 12.2.1 Non-ferromagnetic Sample........................ 77 12.2.2 Ferromagnetic Samples.......................... 78 12.3 Magnetic Particle Hyperthermia Testbed.................... 78 12.3.1 Magnetic Field System.......................... 79 12.3.2 Solenoid Cooling System......................... 81 12.3.3 Magnetic Field Probe Calibration.................... 82 12.3.4 Testbed Characterization......................... 83 12.4 Heating Trials................................... 83 12.4.1 Non-ferromagnetic Sample Heating Trials................ 83 12.4.2 Ferromagnetic Sample Heating Trials.................. 84 13 Experimental Testbed Characterization 86 13.1 Magnetic Field Probe Calibration........................ 86 13.2 Operating Range ................................. 86 13.3 Solenoid Chamber Temperature Stability.................... 88 14 Results and Discussion 90 14.1 Theoretical Results for Laboratory Particles.................. 90 14.2 Experimental Results............................... 95 x 14.3 Theoretical Optimization of SAR and MPH .................. 107 15 Conclusions 109 A LCOrientation.m 111 B Temperature and Field Dependent SWT Code 114 References 118 xi List of Figures 4.1 CPMG spin echo sequence shown with transverse signal response. The axis is time........................................ 20 5.1 Schematics of the five different types of single domain ferromagnetic nanopar- ticles used in this research. Their magnetization orientation is shown on the left, and their dimensions on the left. In the figure c is one half of the mag- netic easy axis length, and a is one half of the magnetic hard axis length of the particle..................................... 23 5.2 Contrast agent sample: multiple layers of agar containing varying concentra- tions of magnetic particles............................. 29 5.3 Image slice shown from the (a) front, (b) side, and (c) top........... 33 6.1 SEM image taken