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Neural Interfacing with Dorsal Root Ganglia: Anatomical Characterization and Electrophysiological Recordings with Novel Electrode Arrays

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Neural Interfacing with Dorsal Root Ganglia: Anatomical Characterization and Electrophysiological Recordings with Novel Electrode Arrays Neural Interfacing with Dorsal Root Ganglia: Anatomical Characterization and Electrophysiological Recordings with Novel Electrode Arrays by Zachariah Sperry A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Biomedical Engineering) at the University of Michigan 2019 Doctoral Committee: Associate Professor Timothy M. Bruns, Chair Associate Professor Cynthia A. Chestek Assistant Professor Scott F. Lempka Associate Professor Parag G. Patil Assistant Research Scientist John P. Seymour Zachariah Sperry [email protected] ORCID iD: 0000-0002-5219-4965 © Zachariah Sperry 2019 Dedication This thesis is dedicated to the memory of my uncle, Pete Aumann. A scientist and mathematician, Uncle Pete was a cerebral man who found great joy in learning and teaching others. He taught me to play and enjoy chess, to patiently engage with challenging mental puzzles, and to take up every opportunity to use my mind for the improvement of our world. He was proud of me pursuing my doctorate, because he knew it would teach me the kind of persistence and scholarship that he so valued. But my uncle also faced many challenges in his life, including bipolar disorder and Crohn’s disease, and he died as I was completing this degree. The diseases he suffered from have no cure today, but the knowledge I have gained as a biomedical engineer gives me hope that one day we will overcome the obstacles in our way. Even within the particular field of neural engineering, promising new therapies are being proposed and developed every year for his particular conditions. As the next chapter of my career begins, I am excited to be a part of these discoveries, and to provide real solutions for people like Uncle Pete. For all the trials he faced, he persisted in his motto “Get busy living!” In his memory, I plan to do just that. ii Acknowledgements No research thesis is completed in a vacuum. This work would not have been possible without the incredible support and encouragement of my wife Christine, who moved to Michigan from Minnesota so I could complete this degree. I also want to acknowledge my parents and sisters, who have always supported, believed in and inspired me to be the best biomedical engineer I can be. I would also like to thank the members of the Peripheral Neural Engineering and Urodynamics Laboratory (pNEURO Lab), particularly my fellow graduate students (Aileen Ouyang, Lauren Zimmerman, Ahmad Jiman, and Elizabeth Bottorff) and my PhD advisor Dr. Tim Bruns. Other critical collaborators include Dr. Scott Lempka, Dr. John Seymour, Dr. Euisik Yoon, Dr. Hillel Chiel, Dr. Paras Patel, Robert Graham, Anastasia Ostrowski, Grant Kulik, Nicholas Peck- Dimit, and Michelle Frazier. My summer internship was funded and supported by Medtronic’s Pelvic Health and Gastric Therapies team, including Dr. Lance Zirpel and Dr. Katie Bittner. I am also grateful to my doctoral committee members for their guidance throughout this process. Research reported in this work was supported by the Craig H. Neilsen Foundation (Grant # 314980) and by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Grant # U18EB021760), the Michigan Institute for Clinical & iii Health Research, which is funded by the National Center for Advancing Translational Studies of the National Institutes of Health (Grant #’s UL1TR000433 and UL1TR002240), the National Science Foundation (Award # 1653080), Seed Funding for Innovative Projects in Neuroscience from the Michigan Brain Initiative Working Group (MiBrain), and the Rackham Predoctoral Fellowship Program. The content is solely the responsibility of the author and does not necessarily represent the official views of the funding organizations. iv Table of Contents Dedication ..................................................................................................................................................................... ii Acknowledgements ..................................................................................................................................................... iii List of Tables ................................................................................................................................................................ vii List of Figures ............................................................................................................................................................. viii List of Appendices ......................................................................................................................................................... x Abstract ........................................................................................................................................................................ xi ................................................................................................................................................ 1 Quantitative Models of Feline Lumbosacral Dorsal Root Ganglia Neuronal Cell Density ........................ 9 Abstract ..................................................................................................................................................................... 9 Introduction ............................................................................................................................................................ 10 Methods .................................................................................................................................................................. 11 Results ..................................................................................................................................................................... 20 Discussion ............................................................................................................................................................... 26 Conclusion ............................................................................................................................................................... 29 Chapter 3: Spatial Models of Cell Distribution in Human Lumbar Dorsal Root Ganglia ........................................... 31 Abstract ................................................................................................................................................................... 31 Introduction ............................................................................................................................................................ 32 v Methods .................................................................................................................................................................. 35 Results ..................................................................................................................................................................... 42 Discussion ............................................................................................................................................................... 55 Conclusion ............................................................................................................................................................... 62 Chapter 4: Flexible Microelectrode Array for Interfacing with the Surface of Neural Ganglia ................................ 63 Abstract ................................................................................................................................................................... 63 Introduction ............................................................................................................................................................ 64 Methods .................................................................................................................................................................. 69 Results ..................................................................................................................................................................... 77 Discussion ............................................................................................................................................................... 83 Conclusion ............................................................................................................................................................... 91 Chapter 5: High-density Neural Recordings from Feline Sacral Dorsal Root Ganglia with Thin-film Array ............. 92 Abstract ................................................................................................................................................................... 92 Introduction ............................................................................................................................................................ 93 Methods .................................................................................................................................................................. 95 Results ................................................................................................................................................................... 103 Discussion ............................................................................................................................................................. 108 Conclusion ............................................................................................................................................................
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