Development and Initial Evaluation of an MR Compatible Preclinical SPECT Insert for Simultaneous SPECT/MR Imaging by Andrew Joseph Rittenbach A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland October, 2015 Abstract Multi-modality medical imaging systems have become increasingly important in research and clinical applications of biomedical imaging. Two complementary imaging modalities that have not yet been fully integrated into a multimodality system are Single Photon Emission Computed Tomography (SPECT) and Magnetic Resonance Imaging (MRI). To this end, our team has developed an MR compatible SPECT insert for simultaneous preclinical SPECT/MR imaging. The SPECT insert’s detector is composed of five rings Cadmium Zinc Telluride (CZT) detector modules and an interchangeable cylindrical multi-pinhole (MPH) collimator. This dissertation discusses several new and significant contributions made towards the development of our SPECT insert. We developed methods to determine optimized design parameters for MPH collimators for the SPECT insert. These methods were used to design two MPH collimators with different imaging resolutions. Simulation results demonstrated that both collimators can be used to obtain artifact-free SPECT images with the designed resolutions. We then developed novel techniques to fabricate the collimators using MR compatible materials. Without proper system calibration and data correction, SPECT images reconstructed from data acquired with our insert exhibit poor image quality. We developed a novel energy calibration method to identify the photopeak of the gamma photons from a Tc-99m source at all 24,320 detector pixels simultaneously and a two- stage detector uniformity correction method to identify and correct for non-uniformities and malfunctioning pixels in the detector modules. Additionally, a method was developed to correct for the drift of electron-hole pairs within the detector modules due to the ii Lorentz force when operating the SPECT insert inside a magnetic field. After applying the system calibration and correction methods to the acquired data, reconstructed SPECT images showed significant improvement in terms of resolution, uniformity, contrast, and artifact reduction. Finally the SPECT insert was evaluated experimentally as a standalone SPECT system and as an insert inside an MRI system for simultaneous SPECT/MR imaging through phantom and small animal studies. The experimental results demonstrated that the SPECT insert met design specifications. Most importantly, results demonstrate that the insert can be used to obtain high quality SPECT images during simultaneous SPECT/MR image acquisition. Dissertation Readers: Dr. Benjamin M. W. Tsui (advisor) Dr. Jingyan Xu iii Acknowledgements There are so many people that I need to thank for helping me during my graduate studies. First and foremost, I would like to thank my advisor Dr. Benjamin M. W. Tsui for taking me on as a research assistant and giving me this amazing opportunity. I have learned so much about not just medical imaging but also how to plan and carry out long term research projects. Much of what I have learned will help me throughout my future endeavors. I would also like to thank Dr. Jingyan Xu, not only for spending time to read this dissertation, but also for the countless hours I spent meeting with her to discuss the many projects that I have been involved with. She always found time in her busy schedule to meet with me. The work described in this dissertation was a collaboration with the Division of MR Research in the Department of Radiology at Johns Hopkins University and Gamma Medica- Ideas, now TriFoil Imaging. I would like to thank Dr. AbdEl-Monem ElSharkawy, the late Dr. William Edelstein, Dr. James Hugg, Dr, Xiaoming Guo, Ang Liu, and Kevin Parnham for their assistance on this project. I also need to thank Martin Stumpf; this work could not have been completed without the DMIP computer cluster, and he made sure that the cluster was up and running. Thanks also goes to LaVahn Tunstall, for assistance with ordering needed materials and activity for all of the experiments I conducted, and to Phil Joslin for managing the accounts needed to purchase the materials. iv Special thanks goes to former DMIP students Dr. Mickel Ghaly, Dr. Xing Rong, and Dr. Xiaolan Wang for the friendships that were developed in lab, in classes, and on the Johns Hopkins Shuttle. Thanks goes out to my good friends Dr. Christopher Rock, Andrew Rock, and Kent Munson. I am happy that we managed to remain friends despite being scattered across the east coast (and for a time, the Atlantic Ocean). I would also like to thank my parents Tom and Betsy Rittenbach, my sisters Lauren and Cynthia Rittenbach, and grandmother Josephine Welter for all of the encouragement that they have given me over the years. I hope that they are proud of the person that I have become. Finally, I absolutely need to thank my wife, Maria Rosario Rittenbach. She has made my time in Baltimore infinitely more enjoyable and I still feel so lucky that I met her here. I love her so much and I can’t wait to see where we go with our lives together. This dissertation is dedicated to her. v Table of Contents Abstract ............................................................................................................................... ii Acknowledgements ............................................................................................................ iv Table of Contents ............................................................................................................... vi List of Tables ................................................................................................................... xiii List of Figures .................................................................................................................. xiv Chapter 1: Introduction and Background ............................................................................ 1 1.1. Motivation .................................................................................................................... 1 1.2. Thesis Goal .................................................................................................................. 3 1.3. Background .................................................................................................................. 4 1.3.1. SPECT Imaging..................................................................................................... 4 1.3.1.1. Traditional SPECT Imaging System Components ......................................... 4 1.3.1.2. Hardware used for Preclinical SPECT Imaging ............................................. 9 1.3.1.3. Semiconductor Photon Detectors ................................................................. 12 1.3.1.4. SPECT System Calibration .......................................................................... 13 1.3.1.5. ML-EM SPECT Image Reconstruction Method .......................................... 15 1.3.2. MR Imaging ........................................................................................................ 18 1.3.2.1. Nuclear Magnetic Resonance ....................................................................... 18 1.3.2.2. MR Imaging System Components ................................................................ 20 1.3.2.3. Traditional MR Image Acquisition ............................................................... 21 vi 1.3.3. Previous Work on Simultaneous SPECT/MR Imaging ...................................... 22 1.3.3.1. Previous Work Conducted by Other Research Groups ................................ 22 1.3.3.2. Previous Work Conducted by Our Research Group ..................................... 23 1.3.4. Improvements of Second Generation SPECT/MR System over Prototype System ....................................................................................................................................... 24 Chapter 2: Methods ........................................................................................................... 26 2.1. Design, Evaluation, and Implementation of Multi-pinhole (MPH) Collimators for the SPECT/MR System .......................................................................................................... 26 2.1.1. Methods to Determine Final Multi-pinhole (MPH) Collimator Design Parameters ....................................................................................................................................... 27 2.1.1.1. Multi-pinhole (MPH) Collimator Design Parameters .................................. 28 2.1.1.2. Multi-pinhole (MPH) Collimator Design Constraints .................................. 34 2.1.1.3. Systematic Methods to Evaluate Multi-pinhole (MPH) Collimator Designs 36 2.1.1.4. Area Based Method for Multi-pinhole (MPH) Collimator Design .............. 41 2.1.1.5. Limitations of the Area Based Method ......................................................... 43 2.1.1.6. Model Based Method for Multi-pinhole (MPH) Collimator Design ............ 46 2.1.1.7. Comparison of Collimator Design Methods ................................................. 52 2.1.2. Methods to Evaluate Final Multi-pinhole (MPH) Collimator Designs Through Simulation ..................................................................................................................... 55 2.1.2.1. Analytical Simulation of Multi-pinhole