Abstract

Reconstructing a map of neuronal connectivity is a critical challenge in contemporary neuroscience. Recent advances in high-throughput serial section electron microscopy (EM) have produced massive 3D image volumes of nanoscale brain tissue for the first time. The resolution of EM allows for individual neurons and their synaptic connections to be directly observed. Recovering neuronal networks by manually tracing each neuronal process at this scale is unmanageable, and therefore researchers are developing automated image processing modules. Thus far, state-of-the-art algorithms focus only on the solution to a particular task (e.g., neuron segmentation or synapse identification). In this manuscript we present the first fully-automated images-to-graphs pipeline (i.e., a pipeline that begins with an imaged volume of neural tissue and produces a brain graph without any human interaction). To evaluate overall performance and select the best parameters and methods, we also develop a metric to assess the quality of the output graphs. We evaluate a set of algorithms and parameters, searching possible operating points to identify the best available brain graph for our assessment metric. Finally, we deploy a reference end-to-end version of the pipeline on a large, publicly available data set. This provides a baseline result and framework for community analysis and future algorithm development and testing. All code and data derivatives have been made publicly available in support of eventually unlocking new biofidelic computational primitives and understanding of neuropathologies.

Highlights

  • Brain tissue volumes imaged using electron microscopy today already contain many thousands of cells that can be resolved at the scale of a single synapse

  • Framework Our tools are built on a distributed processing framework which leverages the LONI Pipeline (Rex et al, 2003) for workflow management, and interfaces with the data and annotation services provided by the Open Connectome Project (OCP)

  • We aimed to build a framework for connectomics processing that was agnostic to the underlying algorithms and provided reusable modules for common steps such as volume dicing, image data download, annotation upload, and annotation merging

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Summary

Introduction

Brain tissue volumes imaged using electron microscopy today already contain many thousands of cells that can be resolved at the scale of a single synapse. The amount of information is daunting: in just 1 mm of brain tissue, we expect petabytes of data containing 105 neurons and 109 synapses (Braitenberg and Schüz, 1991) While this region is very small in physical volume compared to an entire brain, it is roughly the scale of a cortical column, a hypothetical fundamental organizing structure in the cortex (Mountcastle, 1957). Our goal is to transform large 3D electron microscopy volumes of neural tissue into a detailed connectivity map, called a connectome. This approach will directly estimate brain graphs at an unprecedented level of detail. A recent study estimated that manual annotation of a cortical column requires hundreds of thousands of person-years (Helmstaedter et al, 2011)

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