Automatic dendritic spine detection using multiscale dot enhancement filters and sift features

Statistical characterization of morphological changes of dendritic spines is becoming of crucial interest in the field of neurobiology. Automatic detection and segmentation of dendritic spines promises significant reductions on the time spent by the scientists and reduces the subjectivity concerns. In this paper, we present two approaches for automated detection of dendritic spines in 2-photon laser scanning microscopy (2pLSM) images. The first method combines the idea of dot enhancement filters with information from the dendritic skeleton. The second method learns an SVM classifier by utilizing some pre-labeled SIFT feature descriptors and uses the classifier to detect dendritic spines in new images. For the segmentation of detected spines, we employ a watershed-variational segmentation algorithm. We evaluate the proposed approaches by comparing with manual segmentations of domain experts and the results of a noncommercial software, NeuronIQ. Our methods produce promising detection rate with high segmentation accuracy thus can serve as a useful tool for spine analysis

Image informatics strategies for deciphering neuronal network connectivity

Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphologi- cal plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular com- munication and the associated calcium-bursting behaviour. In vitro cultured neu- ronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies

Fuzzy-Logic Based Detection and Characterization of Junctions and Terminations in Fluorescence Microscopy Images of Neurons

Digital reconstruction of neuronal cell morphology is an important step toward understanding the functionality of neuronal networks. Neurons are tree-like structures whose description depends critically on the junctions and terminations, collectively called critical points, making the correct localization and identification of these points a crucial task in the reconstruction process. Here we present a fully automatic method for the integrated detection and characterization of both types of critical points in fluorescence microscopy images of neurons. In view of the majority of our current studies, which are based on cultured neurons, we describe and evaluate the method for application to two-dimensional (2D) images. The method relies on directional filtering and angular profile analysis to extract essential features about the main streamlines at any location in an image, and employs fuzzy logic with carefully designed rules to reason about the feature values in order to make well-informed decisions about the presence of a critical point and its type. Experiments on simulated as well as real images of neurons demonstrate the detection performance of our method. A comparison with the output of two existing neuron reconstruction methods reveals that our method achieves substantially higher detection rates and could provide beneficial information to the reconstruction process

Automated Reconstruction of Neuronal Morphology Based on Local Geometrical and Global Structural Models

Digital reconstruction of neurons from microscope images is an important and challenging problem in neuroscience. In this paper, we propose a model-based method to tackle this problem. We first formulate a model structure, then develop an algorithm for computing it by carefully taking into account morphological characteristics of neurons, as well as the image properties under typical imaging protocols. The method has been tested on the data sets used in the DIADEM competition and produced promising results for four out of the five data sets

Delineating Trees in Noisy 2D Images and 3D Image Stacks

We present a novel approach to fully automated delineation of tree structures in noisy 2D images and 3D image stacks. Unlike earlier methods that rely mostly on local evidence, our method builds a set of candidate trees over many different subsets of points likely to belong to the final one and then chooses the best one according to a global objective function. Since we are not systematically trying to span all nodes, our algorithm is able to eliminate noise while retaining the right tree structure

Automatic Reconstruction of Neural Morphologies with Multi-Scale Tracking

Neurons have complex axonal and dendritic morphologies that are the structural building blocks of neural circuits. The traditional method to capture these morphological structures using manual reconstructions is time-consuming and partly subjective, so it appears important to develop automatic or semi-automatic methods to reconstruct neurons. Here we introduce a fast algorithm for tracking neural morphologies in 3D with simultaneous detection of branching processes. The method is based on existing tracking procedures, adding the machine vision technique of multi-scaling. Starting from a seed point, our algorithm tracks axonal or dendritic arbors within a sphere of a variable radius, then moves the sphere center to the point on its surface with the shortest Dijkstra path, detects branching points on the surface of the sphere, scales it until branches are well separated and then continues tracking each branch. We evaluate the performance of our algorithm on preprocessed data stacks obtained by manual reconstructions of neural cells, corrupted with different levels of artificial noise, and unprocessed data sets, achieving 90% precision and 81% recall in branch detection. We also discuss limitations of our method, such as reconstructing highly overlapping neural processes, and suggest possible improvements. Multi-scaling techniques, well suited to detect branching structures, appear a promising strategy for automatic neuronal reconstructions

Automating the Reconstruction of Neuron Morphological Models: the Rivulet Algorithm Suite

The automatic reconstruction of single neuron cells is essential to enable large-scale data-driven investigations in computational neuroscience. The problem remains an open challenge due to various imaging artefacts that are caused by the fundamental limits of light microscopic imaging. Few previous methods were able to generate satisfactory neuron reconstruction models automatically without human intervention. The manual tracing of neuron models is labour heavy and time-consuming, making the collection of large-scale neuron morphology database one of the major bottlenecks in morphological neuroscience. This thesis presents a suite of algorithms that are developed to target the challenge of automatically reconstructing neuron morphological models with minimum human intervention. We first propose the Rivulet algorithm that iteratively backtracks the neuron fibres from the termini points back to the soma centre. By refining many details of the Rivulet algorithm, we later propose the Rivulet2 algorithm which not only eliminates a few hyper-parameters but also improves the robustness against noisy images. A soma surface reconstruction method was also proposed to make the neuron models biologically plausible around the soma body. The tracing algorithms, including Rivulet and Rivulet2, normally need one or more hyper-parameters for segmenting the neuron body out of the noisy background. To make this pipeline fully automatic, we propose to use 2.5D neural network to train a model to enhance the curvilinear structures of the neuron fibres. The trained neural networks can quickly highlight the fibres of interests and suppress the noise points in the background for the neuron tracing algorithms. We evaluated the proposed methods in the data released by both the DIADEM and the BigNeuron challenge. The experimental results show that our proposed tracing algorithms achieve the state-of-the-art results

Metrics for comparing neuronal tree shapes based on persistent homology

As more and more neuroanatomical data are made available through efforts such as NeuroMorpho.Org and FlyCircuit.org, the need to develop computational tools to facilitate automatic knowledge discovery from such large datasets becomes more urgent. One fundamental question is how best to compare neuron structures, for instance to organize and classify large collection of neurons. We aim to develop a flexible yet powerful framework to support comparison and classification of large collection of neuron structures efficiently. Specifically we propose to use a topological persistence-based feature vectorization framework. Existing methods to vectorize a neuron (i.e, convert a neuron to a feature vector so as to support efficient comparison and/or searching) typically rely on statistics or summaries of morphometric information, such as the average or maximum local torque angle or partition asymmetry. These simple summaries have limited power in encoding global tree structures. Based on the concept of topological persistence recently developed in the field of computational topology, we vectorize each neuron structure into a simple yet informative summary. In particular, each type of information of interest can be represented as a descriptor function defined on the neuron tree, which is then mapped to a simple persistence-signature. Our framework can encode both local and global tree structure, as well as other information of interest (electrophysiological or dynamical measures), by considering multiple descriptor functions on the neuron. The resulting persistence-based signature is potentially more informative than simple statistical summaries (such as average/mean/max) of morphometric quantities-Indeed, we show that using a certain descriptor function will give a persistence-based signature containing strictly more information than the classical Sholl analysis. At the same time, our framework retains the efficiency associated with treating neurons as points in a simple Euclidean feature space, which would be important for constructing efficient searching or indexing structures over them. We present preliminary experimental results to demonstrate the effectiveness of our persistence-based neuronal feature vectorization framework