Foreground Estimation in Neuronal Images With a Sparse-Smooth Model for Robust Quantification

3D volume imaging has been regarded as a basic tool to explore the organization and function of the neuronal system. Foreground estimation from neuronal image is essential in the quantification and analysis of neuronal image such as soma counting, neurite tracing and neuron reconstruction. However, the complexity of neuronal structure itself and differences in the imaging procedure, including different optical systems and biological labeling methods, result in various and complex neuronal images, which greatly challenge foreground estimation from neuronal image. In this study, we propose a robust sparse-smooth model (RSSM) to separate the foreground and the background of neuronal image. The model combines the different smoothness levels of the foreground and the background, and the sparsity of the foreground. These prior constraints together contribute to the robustness of foreground estimation from a variety of neuronal images. We demonstrate the proposed RSSM method could promote some best available tools to trace neurites or locate somas from neuronal images with their default parameters, and the quantified results are similar or superior to the results that generated from the original images. The proposed method is proved to be robust in the foreground estimation from different neuronal images, and helps to improve the usability of current quantitative tools on various neuronal images with several applications.

Cellular anatomy of the mouse primary motor cortex

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input–output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture.

Hidden Markov Modeling for Maximum Probability Neuron Reconstruction

Recent advances in brain clearing and imaging have made it possible to image entire mammalian brains at sub-micron resolution. These images offer the potential to assemble brain-wide atlases of neuron morphology, but manual neuron reconstruction remains a bottleneck. Several automatic reconstruction algorithms exist, but most focus on single neuron images. In this paper, we present a probabilistic reconstruction method, ViterBrain, which combines a hidden Markov state process that encodes neuron geometry with a random field appearance model of neuron flourescence. Our method utilizes dynamic programming to compute the global maximizers of what we call the ``most probable'' neuron path. Our most probable estimation method models the task of reconstructing neuronal processes in the presence of other neurons, and thus is applicable in images with several neurons. Our method operates on image segmentations in order to leverage cutting edge computer vision technology. We applied our algorithm to imperfect image segmentations where false negatives severed neuronal processes, and showed that it can follow axons in the presence of noise or nearby neurons. Additionally, it creates a framework where users can intervene to, for example, fit start and endpoints. The code used in this work is available in our open-source Python package brainlit.

Image enhancement to leverage the 3D morphological reconstruction of single-cell neurons

Motivation To digitally reconstruct the 3D neuron morphologies has long been a major bottleneck in neuroscience. One of the obstacles to automate the procedure is the low signal-background contrast and the large dynamic range of signal and background both within and across images. Results We developed a pipeline to enhance the neurite signal and to suppress the background, with the goal of high signal-background contrast and better within- and between image homogeneity. The performance of the image enhancement was quantitatively verified according to the different figures of merit benchmarking the image quality. Additionally, the method could improve the neuron reconstruction in approximately 1/3 of the cases, with very few cases of degrading the reconstruction. This significantly outperformed three other approaches of image enhancement. Moreover, the compression rate was increased 5 times by average comparing the enhanced to the raw image. All results demonstrated the potential of the proposed method in leveraging the neuroscience providing better 3D morphological reconstruction and lower cost of data storage and transfer. Availability The study is conducted based on the Vaa3D platform and python 3.7.9. The Vaa3D platform is available on the GitHub (https://github.com/Vaa3D). The source code of the proposed image enhancement as a Vaa3D plugin, the source code to benchmark the image quality, and the example image blocks are available under the repository of vaa3d_tools/hackathon/SGuo/imPreProcess. The original fMost images of mouse brains can be found at the BICCN’s Brain Image Library (BIL) (https://www.brainimagelibrary.org). Supplementary information Supplementary data are available at Bioinformatics online.

Nested U-Net Architecture Based Image Segmentation for 3D Neuron Reconstruction

Digital reconstruction of neurons is a critical step in studying neuronal morphology and exploring the working mechanism of the brain. In recent years, the focus of neuronal morphology reconstruction has gradually shifted from single neurons to multiple neurons in a whole brain. Microscopic images of a whole brain often have low signal-to-noise-ratio, discontinuous neuron fragments or weak neuron signals. It is very difficult to segment neuronal signals from the background of these images, which is the first step of most automatic reconstruction algorithms. In this study, we propose a Nested U-Net based Ultra-Tracer model (NUNU-Tracer) for better multiple neurons image segmentation and morphology reconstruction. The NUNU-Tracer utilizes nested U-Net (UNet++) deep network to segment 3D neuron images, reconstructs neuron morphologies under the framework of the Ultra-Tracer and prunes branches of noncurrent tracing neurons. The 3D UNet++ takes a 3D microscopic image as its input, and uses scale-space distance transform and linear fusion strategy to generate the segmentation maps for voxels in the image. It is capable of removing noise, repairing broken neurite patterns and enhancing neuronal signals. We evaluate the performance of the 3D UNet++ for image segmentation and NUNU-Tracer for neuron morphology reconstruction on image blocks and neurons, respectively. Experimental results show that they significantly improve the accuracy and length of neuron reconstructions.