TY - GEN A1 - Hanslovsky, Philipp UR - https://archiv.ub.uni-heidelberg.de/volltextserver/27375/ N2 - Neuroscientists are increasingly convinced that it is necessary to reconstruct the precise wiring and synaptic connectivity of biological nervous systems to eventually decipher their function. The urge to reconstruct ever larger and more complete synaptic wiring diagrams of animal brains has created an entire new subfield of neuroscience: Connectomics. The reconstruction of connectomes is difficult because neurons are both large and small. They project across distances of many millimeters but each individual neurite can be as thin as a few tens of nanomaters. In order to reconstruct all neurites in densely packed neural tissues, it is necessary to image this tissue at nanometer resolution which, today, is only possible with 3D electron microscopy (3D-EM). Over the last decade, 3D-EM has become significantly more reliable than ever before. Today, it is possible to routinely image volumes of up to a cubic millimeter, covering the entire brain of small model organisms such as that of the fruit fly Drosophila melanogaster. These volumes contain tens or hundreds of tera-voxels and cannot be analyzed manually. Efficient computational methods and tools are needed for all stages of connectome reconstruction: (1) assembling distortion and artifact free volumes from serial section EM, (2) precise automatic recon- struction of neurons and synapses, and (3) efficient and user-friendly solutions for visualization and interactive proofreading. In this dissertation, I present new computational methods and tools that I developed to address previously unsolved problems covering all of the above mentioned aspects of EM connectomics. In chapter 2, I present a new method to correct for planar and non-planar axial distortion and to sort unordered section series. This method was instrumental for the first ever acquisition of a complete brain of an adult Drosophila melanogaster imaged with 3D-EM. Machine learning, in particular deep learning, and the availability of public training and test data has had tremendous impact on the automatic reconstruction of neurons and synapses from 3D-EM. In chapter 3, I present a novel artificial neural network architecture that predicts neuron boundaries at quasi-isotropic resolution from non-isotropic 3D-EM. The goal is to create a high-quality over- segmentation with large three-dimensional fragments for faster manual proof- reading. In chapter 4, I present software libraries and tools that I developed to support the processing, visualization, and analysis of large 3D-EM data and connectome reconstructions. Using this software, we generated the largest currently existing training and test data for connectome reconstruction from non-isotropic 3D-EM. I will particularly emphasize my flexible interactive proof-reading tool Paintera that I built on top of the libraries and tools that I have developed over the last four years. CY - Heidelberg TI - Isotropic Reconstruction of Neural Morphology from Large Non-Isotropic 3D Electron Microscopy AV - public ID - heidok27375 KW - Computer Vision Machine Learning AI Neuron Reconstruction Segmentation Big Data Neuroscience Connectomics Y1 - 2019/// ER -