Ran Lu

Donglai Wei, Kisuk Lee, Hanyu Li et al.

Electron microscopy (EM) enables the reconstruction of neural circuits at the level of individual synapses, which has been transformative for scientific discoveries. However, due to the complex morphology, an accurate reconstruction of cortical axons has become a major challenge. Worse still, there is no publicly available large-scale EM dataset from the cortex that provides dense ground truth segmentation for axons, making it difficult to develop and evaluate large-scale axon reconstruction methods. To address this, we introduce the AxonEM dataset, which consists of two 30x30x30 um^3 EM image volumes from the human and mouse cortex, respectively. We thoroughly proofread over 18,000 axon instances to provide dense 3D axon instance segmentation, enabling large-scale evaluation of axon reconstruction methods. In addition, we densely annotate nine ground truth subvolumes for training, per each data volume. With this, we reproduce two published state-of-the-art methods and provide their evaluation results as a baseline. We publicly release our code and data at https://connectomics-bazaar.github.io/proj/AxonEM/index.html to foster the development of advanced methods.

Ran Lu, Aleksandar Zlateski, H. Sebastian Seung

Many approaches to 3D image segmentation are based on hierarchical clustering of supervoxels into image regions. Here we describe a distributed algorithm capable of handling a tremendous number of supervoxels. The algorithm works recursively, the regions are divided into chunks that are processed independently in parallel by multiple workers. At each round of the recursive procedure, the chunk size in all dimensions are doubled until a single chunk encompasses the entire image. The final result is provably independent of the chunking scheme, and the same as if the entire image were processed without division into chunks. This is nontrivial because a pair of adjacent regions is scored by some statistical property (e.g. mean or median) of the affinities at the interface, and the interface may extend over arbitrarily many chunks. The trick is to delay merge decisions for regions that touch chunk boundaries, and only complete them in a later round after the regions are fully contained within a chunk. We demonstrate the algorithm by clustering an affinity graph with over 1.5 trillion edges between 135 billion supervoxels derived from a 3D electron microscopic brain image.

Sharmishtaa Seshamani, Leila Elabbady, Casey Schneider-Mizell et al.

Morphology based analysis of cell types has been an area of great interest to the neuroscience community for several decades. Recently, high resolution electron microscopy (EM) datasets of the mouse brain have opened up opportunities for data analysis at a level of detail that was previously impossible. These datasets are very large in nature and thus, manual analysis is not a practical solution. Of particular interest are details to the level of post synaptic structures. This paper proposes a fully automated framework for analysis of post-synaptic structure based neuron analysis from EM data. The processing framework involves shape extraction, representation with an autoencoder, and whole cell modeling and analysis based on shape distributions. We apply our novel framework on a dataset of 1031 neurons obtained from imaging a 1mm x 1mm x 40 micrometer volume of the mouse visual cortex and show the strength of our method in clustering and classification of neuronal shapes.

Kisuk Lee, Ran Lu, Kyle Luther et al.

We show dense voxel embeddings learned via deep metric learning can be employed to produce a highly accurate segmentation of neurons from 3D electron microscopy images. A "metric graph" on a set of edges between voxels is constructed from the dense voxel embeddings generated by a convolutional network. Partitioning the metric graph with long-range edges as repulsive constraints yields an initial segmentation with high precision, with substantial accuracy gain for very thin objects. The convolutional embedding net is reused without any modification to agglomerate the systematic splits caused by complex "self-contact" motifs. Our proposed method achieves state-of-the-art accuracy on the challenging problem of 3D neuron reconstruction from the brain images acquired by serial section electron microscopy. Our alternative, object-centered representation could be more generally useful for other computational tasks in automated neural circuit reconstruction.

Kisuk Lee, Nicholas Turner, Thomas Macrina et al.

Neural circuits can be reconstructed from brain images acquired by serial section electron microscopy. Image analysis has been performed by manual labor for half a century, and efforts at automation date back almost as far. Convolutional nets were first applied to neuronal boundary detection a dozen years ago, and have now achieved impressive accuracy on clean images. Robust handling of image defects is a major outstanding challenge. Convolutional nets are also being employed for other tasks in neural circuit reconstruction: finding synapses and identifying synaptic partners, extending or pruning neuronal reconstructions, and aligning serial section images to create a 3D image stack. Computational systems are being engineered to handle petavoxel images of cubic millimeter brain volumes.

Nicholas Turner, Kisuk Lee, Ran Lu et al.

Connectomics aims to recover a complete set of synaptic connections within a dataset imaged by volume electron microscopy. Many systems have been proposed for locating synapses, and recent research has included a way to identify the synaptic partners that communicate at a synaptic cleft. We re-frame the problem of identifying synaptic partners as directly generating the mask of the synaptic partners from a given cleft. We train a convolutional network to perform this task. The network takes the local image context and a binary mask representing a single cleft as input. It is trained to produce two binary output masks: one which labels the voxels of the presynaptic partner within the input image, and another similar labeling for the postsynaptic partner. The cleft mask acts as an attentional gating signal for the network. We find that an implementation of this approach performs well on a dataset of mouse somatosensory cortex, and evaluate it as part of a combined system to predict both clefts and connections.