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Brain Mapping Methods: Segmentation, Registration, and Connectivity Analysis UCLA UCLA Electronic Theses and Dissertations Title Brain Mapping Methods: Segmentation, Registration, and Connectivity Analysis Permalink https://escholarship.org/uc/item/1jt7m230 Author Prasad, Gautam Publication Date 2013 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California University of California Los Angeles Brain Mapping Methods: Segmentation, Registration, and Connectivity Analysis A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Computer Science by Gautam Prasad 2013 c Copyright by Gautam Prasad 2013 Abstract of the Dissertation Brain Mapping Methods: Segmentation, Registration, and Connectivity Analysis by Gautam Prasad Doctor of Philosophy in Computer Science University of California, Los Angeles, 2013 Professor Demetri Terzopoulos, Chair We present a collection of methods that model and interpret information represented in structural magnetic resonance imaging (MRI) and diffusion MRI images of the living hu- man brain. Our solution to the problem of brain segmentation in structural MRI combines artificial life and deformable models to develop a customizable plan for segmentation real- ized as cooperative deformable organisms. We also present work to represent and register white matter pathways as described in diffusion MRI. Our method represents these path- ways as maximum density paths (MDPs), which compactly represent information and are compared using shape based registration for population studies. In addition, we present a group of methods focused on connectivity in the brain. These include an optimization for a global probabilistic tractography algorithm that computes fibers representing connectivity pathways in tissue, a novel maximum-flow based measure of connectivity, a classification framework identifying Alzheimer's disease based on connectivity measures, and a statisti- cal framework to find the optimal partition of the brain for connectivity analysis. These methods seek to advance our understanding and analysis of neuroimaging data from crucial pre-processing steps to our fundamental understanding of connectivity in the brain. ii The dissertation of Gautam Prasad is approved. Alan L. Yuille Stanley Osher Paul M. Thompson Demetri Terzopoulos, Committee Chair University of California, Los Angeles 2013 iii Table of Contents 1 Introduction :::::::::::::::::::::::::::::::::::::: 1 1.1 Brain Segmentation................................3 1.2 White Matter Representation & Registration..................5 1.3 Connectivity....................................6 2 Brain Segmentation ::::::::::::::::::::::::::::::::: 11 2.1 Skull-Stripping with Deformable Organisms.................. 11 2.1.1 Introduction................................ 11 2.1.2 Methods.................................. 13 2.1.3 Results................................... 20 2.2 Deformable Organisms and Error Learning for Brain Segmentation..... 21 2.2.1 Introduction................................ 21 2.2.2 Methods.................................. 23 2.2.3 Results................................... 32 3 White Matter Representation & Registration ::::::::::::::::: 34 3.1 Atlas-Based Fiber Clustering for Multi-Subject Analysis of High Angular Res- olution Diffusion Imaging Tractography..................... 34 3.1.1 Introduction................................ 34 3.1.2 Methods.................................. 36 3.1.3 Results................................... 41 3.2 White Matter Tract Analysis in 454 Adults using Maximum Density Paths. 43 3.2.1 Introduction................................ 43 iv 3.2.2 Methods.................................. 44 3.2.3 Results................................... 50 4 Connectivity ::::::::::::::::::::::::::::::::::::: 59 4.1 Tractography Density and Network Measures in Alzheimer's Disease..... 59 4.1.1 Introduction................................ 59 4.1.2 Methods.................................. 60 4.1.3 Results................................... 67 4.2 Flow-Based Network Measures of Brain Connectivity in Alzheimer's Disease................................ 69 4.2.1 Introduction................................ 69 4.2.2 Methods.................................. 71 4.2.3 Results................................... 77 4.3 Brain Connectivity and Network Measures in Alzheimer's Disease Identification 78 4.3.1 Introduction................................ 78 4.3.2 Methods.................................. 79 4.3.3 Results................................... 85 4.4 Optimizing Nodes in Brain Connectivity Analyses using Markov Chain Monte Carlo Methods for Alzheimer's Disease Classification............. 86 4.4.1 Introduction................................ 86 4.4.2 Methods.................................. 88 4.4.3 Results................................... 93 5 Conclusion ::::::::::::::::::::::::::::::::::::::: 95 5.1 Brain Segmentation................................ 95 v 5.2 White Matter Representation & Registration.................. 96 5.3 Connectivity.................................... 97 5.4 Future Work.................................... 99 vi List of Figures 2.1 T1 MR image with manually delineated brain................. 12 2.2 3-Means classification of a T1 MR image.................... 14 2.3 Steps of the skull-stripping algorithm...................... 17 2.4 Sequential steps of the organisms........................ 18 2.5 Interactions between the organisms....................... 19 3.1 Tractography fibers and region intersections.................. 52 3.2 Fiber selection example.............................. 53 3.3 Median filtering of fibers and path representation............... 54 3.4 Maximum density paths for two tractography methods............ 54 3.5 Fractional anisotropy along maximum density paths.............. 55 3.6 Pipeline for statistics analysis of white matter................. 56 3.7 Hough transform fibers.............................. 56 3.8 Significant areas along Hough maximum density paths............ 57 3.9 Significant areas in streamline maximum density paths............ 58 4.1 Directions lookup table.............................. 65 4.2 Different densities of fibers in the Hough method............... 66 4.3 Sample connectivity matrix........................... 67 4.4 Tests between disease states comparing p-values................ 68 4.5 Pipeline of the flow algorithm.......................... 71 4.6 Comparison of the fiber and flow connectivity matrix............. 76 4.7 An example of the standard connectivity matrix................ 82 4.8 Overview of feature selection algorithm..................... 85 vii 4.9 Random patches used over the cortex...................... 89 viii List of Tables 2.1 Results of automatic segmentation algorithms................. 20 2.2 Plan for each organism to skull-strip an MRI image.............. 30 2.3 Metrics comparing manual and automatic segmentation............ 33 2.4 Metrics comparing manual and learning segmentation............. 33 4.1 Highest effect size results in each disease state test............... 69 4.2 Table of most significant network measures in both methods......... 77 4.3 Results of the SVM cross-valisation classification................ 86 4.4 Comparison of classification with different cortical segmentations....... 94 ix Acknowledgments I thank Professor Demetri Terzopoulos for being my advisor in the computer science de- partment during my masters and doctorate work at UCLA. He provided valuable support, insight, and discussion for many of our research projects. In addition, he assisted with the es- sential details of realizing a PhD, which ranged from designing a prospectus and dissertation to how to prepare myself for a career in research. Professor Paul Thompson provided endless support and encouragement during my doc- torate work and for this I am exceedingly grateful. He enthusiastically supported my first attempts at publishing my own research and put the quality of my work into perspective. In all my subsequent work he played a key role in helping with financial, equipment, data, and collaborative support. His ever positive attitude made our academic accomplishments seem not only possible, but easy. To Professors Stanley Osher and Alan Yuille I am very appreciative of their membership in my doctoral committee and for contributing their time and expertise to asses and improve my work. The Laboratory of Neuro Imaging at UCLA has provided an amazing and inspiring environment for research and I have benefited substantially from working and collaborating with an unparalleled group of researchers. Shantanu Joshi and Anand Joshi were ready for any technical question I asked and made research simple and within reach. Their pep talks pushed me to work harder and dream bigger. Neda Jahanshad, Omid Kohannim, Eugenio Inglesias, and Vishal Patel were astounding and motivating examples of graduate students and treated me with a lot of kindness. Julio Villalon and Talia Nir were indispensable in many projects and their commitment to research made it exciting. My mom and nani deserve thanks for making life fun and always being up for my pseudo- intellectual discussions on the meaning of life. I thank my dad, dada, dadi, nana, and mama for making a PhD seem perfunctory and genetically engineering me to study physics. Oliver, Keith, Letitia, mausi, mausa, Zak, Mira, and chote mama deserve thanks for entertaining x me with the idea that there is a life outside of academia. I'm also thankful for Nina's love, support, and guidance and concede that a fifteen year PhD may
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