VESICLE: Volumetric Evaluation of Synaptic Interfaces using Computer vision at Large Scale

An open challenge problem at the forefront of modern neuroscience is to obtain a comprehensive mapping of the neural pathways that underlie human brain function; an enhanced understanding of the wiring diagram of the brain promises to lead to new breakthroughs in diagnosing and treating neurological disorders. Inferring brain structure from image data, such as that obtained via electron microscopy (EM), entails solving the problem of identifying biological structures in large data volumes. Synapses, which are a key communication structure in the brain, are particularly difficult to detect due to their small size and limited contrast. Prior work in automated synapse detection has relied upon time-intensive biological preparations (post-staining, isotropic slice thicknesses) in order to simplify the problem. This paper presents VESICLE, the first known approach designed for mammalian synapse detection in anisotropic, non-post-stained data. Our methods explicitly leverage biological context, and the results exceed existing synapse detection methods in terms of accuracy and scalability. We provide two different approaches - one a deep learning classifier (VESICLE-CNN) and one a lightweight Random Forest approach (VESICLE-RF) to offer alternatives in the performance-scalability space. Addressing this synapse detection challenge enables the analysis of high-throughput imaging data soon expected to reach petabytes of data, and provide tools for more rapid estimation of brain-graphs. Finally, to facilitate community efforts, we developed tools for large-scale object detection, and demonstrated this framework to find $\approx$ 50,000 synapses in 60,000 $\mu m ^3$ (220 GB on disk) of electron microscopy data.

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.