Enabling Scalable Neurocartography: Images to Graphs for Discovery

In recent years, advances in technology have enabled researchers to ask new questions predicated on the collection and analysis of big datasets that were previously too large to study. More specifically, many fundamental questions in neuroscience require studying brain tissue at a large scale to discover emergent properties of neural computation, consciousness, and etiologies of brain disorders. A major challenge is to construct larger, more detailed maps (e.g., structural wiring diagrams) of the brain, known as connectomes. Although raw data exist, obstacles remain in both algorithm development and scalable image analysis to enable access to the knowledge within these data volumes. This dissertation develops, combines and tests state-of-the-art algorithms to estimate graphs and glean other knowledge across six orders of magnitude, from millimeter-scale magnetic resonance imaging to nanometer-scale electron microscopy. This work enables scientific discovery across the community and contributes to the tools and services offered by NeuroData and the Open Connectome Project. Contributions include creating, optimizing and evaluating the first known fully-automated brain graphs in electron microscopy data and magnetic resonance imaging data; pioneering approaches to generate knowledge from X-Ray tomography imaging; and identifying and solving a variety of image analysis challenges associated with building graphs suitable for discovery. These methods were applied across diverse datasets to answer questions at scales not previously explored

Computing Scalable Multivariate Glocal Invariants of Large (Brain-) Graphs

Graphs are quickly emerging as a leading abstraction for the representation of data. One important application domain originates from an emerging discipline called "connectomics". Connectomics studies the brain as a graph; vertices correspond to neurons (or collections thereof) and edges correspond to structural or functional connections between them. To explore the variability of connectomes---to address both basic science questions regarding the structure of the brain, and medical health questions about psychiatry and neurology---one can study the topological properties of these brain-graphs. We define multivariate glocal graph invariants: these are features of the graph that capture various local and global topological properties of the graphs. We show that the collection of features can collectively be computed via a combination of daisy-chaining, sparse matrix representation and computations, and efficient approximations. Our custom open-source Python package serves as a back-end to a Web-service that we have created to enable researchers to upload graphs, and download the corresponding invariants in a number of different formats. Moreover, we built this package to support distributed processing on multicore machines. This is therefore an enabling technology for network science, lowering the barrier of entry by providing tools to biologists and analysts who otherwise lack these capabilities. As a demonstration, we run our code on 120 brain-graphs, each with approximately 16M vertices and up to 90M edges.Comment: Published as part of 2013 IEEE GlobalSIP conferenc

An Automated Images-to-Graphs Framework for High Resolution Connectomics

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 toward eventually unlocking new biofidelic computational primitives and understanding of neuropathologies.Comment: 13 pages, first two authors contributed equally V2: Added additional experiments and clarifications; added information on infrastructure and pipeline environmen

Neural Reconstruction Integrity: A Metric for Assessing the Connectivity Accuracy of Reconstructed Neural Networks

Neuroscientists are actively pursuing high-precision maps, or graphs consisting of networks of neurons and connecting synapses in mammalian and non-mammalian brains. Such graphs, when coupled with physiological and behavioral data, are likely to facilitate greater understanding of how circuits in these networks give rise to complex information processing capabilities. Given that the automated or semi-automated methods required to achieve the acquisition of these graphs are still evolving, we developed a metric for measuring the performance of such methods by comparing their output with those generated by human annotators (“ground truth” data). Whereas classic metrics for comparing annotated neural tissue reconstructions generally do so at the voxel level, the metric proposed here measures the “integrity” of neurons based on the degree to which a collection of synaptic terminals belonging to a single neuron of the reconstruction can be matched to those of a single neuron in the ground truth data. The metric is largely insensitive to small errors in segmentation and more directly measures accuracy of the generated brain graph. It is our hope that use of the metric will facilitate the broader community's efforts to improve upon existing methods for acquiring brain graphs. Herein we describe the metric in detail, provide demonstrative examples of the intuitive scores it generates, and apply it to a synthesized neural network with simulated reconstruction errors. Demonstration code is available

Neural Reconstruction Integrity: A Metric for Assessing the Connectivity Accuracy of Reconstructed Neural Networks

Neuroscientists are actively pursuing high-precision maps, or graphs consisting of networks of neurons and connecting synapses in mammalian and non-mammalian brains. Such graphs, when coupled with physiological and behavioral data, are likely to facilitate greater understanding of how circuits in these networks give rise to complex information processing capabilities. Given that the automated or semi-automated methods required to achieve the acquisition of these graphs are still evolving, we developed a metric for measuring the performance of such methods by comparing their output with those generated by human annotators (“ground truth” data). Whereas classic metrics for comparing annotated neural tissue reconstructions generally do so at the voxel level, the metric proposed here measures the “integrity” of neurons based on the degree to which a collection of synaptic terminals belonging to a single neuron of the reconstruction can be matched to those of a single neuron in the ground truth data. The metric is largely insensitive to small errors in segmentation and more directly measures accuracy of the generated brain graph. It is our hope that use of the metric will facilitate the broader community's efforts to improve upon existing methods for acquiring brain graphs. Herein we describe the metric in detail, provide demonstrative examples of the intuitive scores it generates, and apply it to a synthesized neural network with simulated reconstruction errors. Demonstration code is available