Morphology of Memory: Creating a web-based 3D interactive resource to teach the anatomy of the human hippocampus by Alisa M. Brandt A thesis submitted to Johns Hopkins University in conformity with the requirements for the degree of Master of Arts Baltimore, Maryland March, 2019 © 2019 Alisa Brandt All Rights Reserved ABSTRACT The hippocampus is a critical region of the brain involved in memory and learning. It has been widely researched in animals and humans due to its role in consolidating new experiences into long-term declarative memories and its vulnerability in neurodegenerative diseases. The hippocampus is a complex, curved structure containing many interconnected regions that consist of distinct cell types. Despite the importance of understanding the normal state of hippocampal anatomy for studying its functions and the disease processes that affect it, didactic educational resources are severely limited. The literature on the hippocampus is expansive and detailed, but a communication gap exists between researchers presenting hippocampal data and those seeking to improve their understanding of this part of the brain. The hippocampus is typically viewed in a two-dimensional fashion; students and scientists have diffculty visualizing its three-dimensional anatomy and its structural relationships in space. To improve understanding of the hippocampus, an interactive, web-based educational resource was created containing a pre-rendered 3D animation and manipulable 3D models of hippocampal regions. Segmentations of magnetic resonance imaging data were modifed and sculpted to build idealized anatomical models suitable for teaching purposes. These models were animated in combination with illustrations and narration to introduce the viewer to the subject, and the completed animation was uploaded online and embedded into the interactive. A separate section of the interactive allows the user to rotate the models, hide and show different regions, and access additional explanatory text. The user interface and interactivity were coded to allow exploration of hippocampal regions and navigation between sections of the resource. The results of this project provide a didactic and accessible visualization for graduate students, researchers, clinicians, and other individuals involved in neuroscience. The animation and interactive models allow users to reinforce their understanding of 3D hippocampal anatomy and connectivity. By improving visual understanding of the hippocampus, this project aims to advance the communication and scientifc study of hippocampus-related topics, such as epilepsy and Alzheimer’s disease. Alisa M. Brandt ii CHAIRPERSONS OF THE SUPERVISORY COMMITTEE David Nauen, MD, PhD, Preceptor Assistant Professor, Division of Neuropathology, Department of Pathology The Johns Hopkins University School of Medicine Lydia Gregg, MA, CMI, FAMI, Department Advisor Associate Professor, Division of Interventional Neuroradiology, Department of Radiology and Radiological Science and Department of Art as Applied to Medicine The Johns Hopkins University School of Medicine Michael I. Miller, PhD, Content Advisor Director, Department of Biomedical Engineering Co-Director, Kavli Neuroscience Discovery Institute The Johns Hopkins University School of Medicine and Whiting School of Engineering iii ACKNOWLEDGMENTS This project has been a remarkable journey of learning and insight. It would not have been possible without the support and expertise of many individuals, and I am so grateful that I had this opportunity to work with them and study with them. I would like to extend my sincerest thanks to: Lydia Gregg, my advisor and Associate Professor in the Department of Art as Applied to Medicine. Thank you for your skillful guidance, your patience, your honest feedback, and your supportive energy throughout this project. You have inspired me and helped me achieve what I thought was initially beyond my reach. Dr. David Nauen, my preceptor, Assistant Professor and neuropathologist in the Department of Pathology, for his enthusiasm and contributions. Thank you for sharing your work, your ideas, and your extensive knowledge with me, and for your time during the many elucidating discussions we had about this project. Dr. Michael Miller and the Center for Imaging Science, for providing invaluable segmentation data and content feedback. Special thanks to Timothy Brown and Dr. Daniel Tward for our in-depth discussions and their presentation of their work. Dr. Jianyang Zhang, at the New York University School of Medicine, for providing diffusion data of a hippocampal specimen and assisting with segmentation software. Thank you for your expertise in preparing this informative dataset. Dr. James Knierim, for his feedback on hippocampal connectivity; Dr. Tilak Ratnanather, for his helpful comments; and the four graduate students I had the pleasure of meeting, for sharing their perspectives and experiences while studying the hippocampus. The Faculty and Staff of the Department of Art as Applied to Medicine, with special thanks to: Corinne Sandone, for her leadership and unwavering support; David Rini, for his approachability and for taking care of all things 3D; Jennifer Fairman, for her vibrant energy and for always being willing to assist; Tim Phelps, for his sharp eye and fery humor; Gary Lees, for his perception and indispensable knowledge of the archives; Juan Garcia, for his inspiring drive for accuracy and clarity; Sarah Poynton, for her mastery of effective writing; Norman Barker, for his passion and knowledge of photography; Dacia Balch, for her thoughtfulness and incredible coordination; and iv Carol Pfeffer, for her warmth and constant encouragement. Thank you for making the Department such a motivating and comfortable place to study and learn with the highest standards. My classmates in the Class of 2019: Brittany Bennett, Insil Choi, Cecilia Johnson, Lohitha Kethu, and Vondel Mahon, for their companionship and kindness, their artistry and beautiful work, and their laughter. I am glad to have walked this path with you. My parents: Kyoko Kubota and Dwayne Brandt, for their support and encouragement throughout this project and throughout my life. Thank you for always being there to listen, no matter how far I am from home. Finally, special thanks to The Vesalius Trust for Visual Communication in the Health Sciences for their generous support of this project. v TABLE OF CONTENTS Abstract ....................................................................................................................................................ii Acknowledgments ..................................................................................................................................iv Table of Contents ....................................................................................................................................vi List of Figures .........................................................................................................................................ix List of Abbreviations .............................................................................................................................xii Introduction.............................................................................................................................................. 1 An overview of the human hippocampus ................................................................................................1 Clarifcation of terminology ............................................................................................................3 Architecture of the adult hippocampal formation .......................................................................... 4 Memory generation via the perforant path and the hippocampal circuit ....................................... 7 Existing educational resources ...................................................................................................... 10 Animation and interactive media as learning tools ...................................................................... 12 WebGL-based 3D visualization .................................................................................................... 12 Objectives ...................................................................................................................................... 13 Audiences ...................................................................................................................................... 13 Materials and Methods .......................................................................................................................... 14 Sources of data .............................................................................................................................. 14 Overview of software .................................................................................................................... 15 Preparation of diffusion data for segmentation in 3D Slicer ........................................................ 16 Segmentation in 3D Slicer ............................................................................................................. 17 Creation of 3D models ................................................................................................................... 25 Hippocampal models ............................................................................................................ 25 1. Sculpting in ZBrush ................................................................................................