The Sørensen-Dice index (SDI) is a widely used measure for evaluating medical image segmentation algorithms. It offers a standardized measure of segmentation accuracy which has proven useful. However, it offers diminishing insight when the number of objects is unknown, such as in white matter lesion segmentation of multiple sclerosis (MS) patients. We present a refinement for finer grained parsing of SDI results in situations where the number of objects is unknown. We explore these ideas with two case studies showing what can be learned from our two presented studies. Our first study explores an inter-rater comparison, showing that smaller lesions cannot be reliably identified. In our second case study, we demonstrate fusing multiple MS lesion segmentation algorithms based on the insights into the algorithms provided by our analysis to generate a segmentation that exhibits improved performance. This work demonstrates the wealth of information that can be learned from refined analysis of medical image segmentations. Segmentation is one of the cornerstones of image processing; it is the process of automatic or semi-automatic detection of boundaries within an image. In a medical imaging context, segmentation is concerned with differentiating tissue classes (i.e., white matter vs. gray matter in the brain), identifying anatomy, or pathology. Motivating examples for the use of segmentation in medical imaging include content based image retrieval 1 , tumor delineation 2 , cell detection 3 and motion tracking 4 , object measurement for size 5 , shape analysis 6 evaluation, and myriad other uses 7-47. The review articles by Pham et al. 48 and Sharma et al. 49 are a useful resource, providing an overview of the different applications of segmentation in medical imaging. A common feature of all this literature is the evaluation of the proposed segmentation algorithm either in comparison to previous work, or more importantly, to some manual/digital gold-standard. In fact, it is impossible to report new segmentation methods without such evaluation; it therefore follows that evaluating medical image segmentation algorithms is important. There have been many methods employed in the evaluation of medical image segmentation algorithms. Voxel-based methods such as intra-class correlation coefficient (ICC) 50,51 , Sørensen-Dice Index 52,53 , and Jaccard coefficient 54 can provide insight about the agreement between a ground truth segmentation and an algorithm

An open challenge 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, error-prone biological preparations (isotropic slicing, post-staining) in order to simplify the problem. This paper presents VESICLE, the first known approach designed for mammalian synapse detection in anisotropic, non-poststained 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 -a deep learning classifier (VESICLE-CNN) and 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 that is soon expected to produce petabytes of data, and provides 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 ⇡ 50,000 synapses in 60,000 µm 3 (220 GB on disk) of electron microscopy data.Figure 1: Previous work on synapse detection has focused on isotropic post-stained data (left), which shows crisp membranes and dark fuzzy post synaptic densities (arrows) from all orientations. The alternative imaging technique of non post-stained, anisotropic data (middle, right) promises higher throughput, lack of staining artifacts, reduction in lost slices, and less demanding data storage requirements -all critically important for high-throughput connectomics. The XZ plane of a synapse in anisotropic data is shown (right), illustrating the effect of lower resolution. We address this more challenging environment, in which membranes appear fuzzier and are harder to distinguish from synaptic contacts. Data courtesy of Graham Knott (left) and Jeff Lichtman (middle, right).In Figure 1, we provide examples demonstrating the challenging setting of our detection task. Figure 2 illustrates the importance of leveraging contextual information, especially neurotransmitter-containing vesicles and cell membranes. Finally, Figure 3 presents a summary of classifier performance; visualizations of the results are not shown here, but are available in the full paper and on our website. Our code and data are open source and available at: openconnecto.me/vesicle. The detection task is to identify synapses shown in green (upper right). These synapses are kn...

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.

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.

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