Multiphoton Excitation Microscopy for the Reconstruction and Analysis of Single Neuron Morphology

Abstract Recent whole brain mapping projects are collecting large-scale 3D images using powerful and informative modalities, such as STPT, fMOST, VISoR, or MRI. Registration of these multi-dimensional whole-brain images onto a standard atlas is essential for characterizing neuron types and constructing brain wiring diagrams. However, cross-modality image registration is challenging due to intrinsic variations of brain anatomy and artifacts resulted from different sample preparation methods and imaging modalities. We introduced a cross-modality registration method, called mBrainAligner, which uses coherent landmark mapping as well as deep neural networks to align whole mouse brain images to the standard Allen Common Coordinate Framework atlas. We also built a single cell resolution atlas using the fMOST modality, and used our method to generate whole brain map of 3D full single neuron morphology and neuron cell types.

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Detection and skeletonization of single neurons and tracer injections using topological methods

10.1101/2020.03.21.000323 ◽

2020 ◽

Author(s):

Dingkang Wang ◽

Lucas Magee ◽

Bing-Xing Huo ◽

Samik Banerjee ◽

Xu Li ◽

...

Keyword(s):

Single Neuron ◽

Image Data ◽

Connectivity Matrix ◽

Consensus Tree ◽

Neuron Morphology ◽

Tracer Injection ◽

Topological Methods ◽

Global Properties ◽

Branching Patterns ◽

Performance Gains

Neuroscientific data analysis has traditionally relied on linear algebra and stochastic process theory. However, the tree-like shapes of neurons cannot be described easily as points in a vector space (the subtraction of two neuronal shapes is not a meaningful operation), and methods from computational topology are better suited to their analysis. Here we introduce methods from Discrete Morse (DM) Theory to extract the tree-skeletons of individual neurons from volumetric brain image data, and to summarize collections of neurons labelled by tracer injections. Since individual neurons are topologically trees, it is sensible to summarize the collection of neurons using a consensus tree-shape that provides a richer information summary than the traditional regional ‘connectivity matrix’ approach. The conceptually elegant DM approach lacks hand-tuned parameters and captures global properties of the data as opposed to previous approaches which are inherently local. For individual skeletonization of sparsely labelled neurons we obtain substantial performance gains over state-of-the-art non-topological methods (over 10% improvements in precision and faster proofreading). The consensus-tree summary of tracer injections incorporates the regional connectivity matrix information, but in addition captures the collective collateral branching patterns of the set of neurons connected to the injection site, and provides a bridge between single-neuron morphology and tracer-injection data.

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