Feasibility of 3D Reconstruction of Neural Morphology Using Expansion Microscopy and Barcode-Guided Agglomeration

We here introduce and study the properties, via computer simulation, of a candidate automated approach to algorithmic reconstruction of dense neural morphology, based on simulated data of the kind that would be obtained via two emerging molecular technologies—expansion microscopy (ExM) and in-situ m...

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Bibliographic Details
Main Authors: Yoon, Young Gyu, Dai, Peilun, Wohlwend, Jeremy, Chang, Jae-Byum, Marblestone, Adam Henry, Boyden, Edward
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Published: Frontiers Research Foundation 2018
Online Access:http://hdl.handle.net/1721.1/115370
https://orcid.org/0000-0003-1812-6421
https://orcid.org/0000-0002-1680-0526
https://orcid.org/0000-0003-2055-4900
https://orcid.org/0000-0002-0419-3351
Description
Summary:We here introduce and study the properties, via computer simulation, of a candidate automated approach to algorithmic reconstruction of dense neural morphology, based on simulated data of the kind that would be obtained via two emerging molecular technologies—expansion microscopy (ExM) and in-situ molecular barcoding. We utilize a convolutional neural network to detect neuronal boundaries from protein-tagged plasma membrane images obtained via ExM, as well as a subsequent supervoxel-merging pipeline guided by optical readout of information-rich, cell-specific nucleic acid barcodes. We attempt to use conservative imaging and labeling parameters, with the goal of establishing a baseline case that points to the potential feasibility of optical circuit reconstruction, leaving open the possibility of higher-performance labeling technologies and algorithms. We find that, even with these conservative assumptions, an all-optical approach to dense neural morphology reconstruction may be possible via the proposed algorithmic framework. Future work should explore both the design-space of chemical labels and barcodes, as well as algorithms, to ultimately enable routine, high-performance optical circuit reconstruction.