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

Automated Three-Dimensional Detection and Shape Classification of Dendritic Spines from Fluorescence Microscopy Images

A fundamental challenge in understanding how dendritic spine morphology controls learning and memory has been quantifying three-dimensional (3D) spine shapes with sufficient precision to distinguish morphologic types, and sufficient throughput for robust statistical analysis. The necessity to analyze large volumetric data sets accurately, efficiently, and in true 3D has been a major bottleneck in deriving reliable relationships between altered neuronal function and changes in spine morphology. We introduce a novel system for automated detection, shape analysis and classification of dendritic spines from laser scanning microscopy (LSM) images that directly addresses these limitations. The system is more accurate, and at least an order of magnitude faster, than existing technologies. By operating fully in 3D the algorithm resolves spines that are undetectable with standard two-dimensional (2D) tools. Adaptive local thresholding, voxel clustering and Rayburst Sampling generate a profile of diameter estimates used to classify spines into morphologic types, while minimizing optical smear and quantization artifacts. The technique opens new horizons on the objective evaluation of spine changes with synaptic plasticity, normal development and aging, and with neurodegenerative disorders that impair cognitive function

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

Dendritic spine shape analysis using disjunctive normal shape models

Analysis of dendritic spines is an essential task to understand the functional behavior of neurons. Their shape variations are known to be closely linked with neuronal activities. Spine shape analysis in particular, can assist neuroscientists to identify this relationship. A novel shape representation has been proposed recently, called Disjunctive Normal Shape Models (DNSM). DNSM is a parametric shape representation and has proven to be successful in several segmentation problems. In this paper, we apply this parametric shape representation as a feature extraction algorithm. Further, we propose a kernel density estimation (KDE) based classification approach for dendritic spine classification. We evaluate our proposed approach on a data set of 242 spines, and observe that it outperforms the classical morphological feature based approach for spine classification. Our probabilistic framework also provides a way to examine the separability of spine shape classes in the likelihood ratio space, which leads to further insights about the nature of the shape analysis problem in this context