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

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Yoon YG, Dai P, Wohlwend J, Chang JB, Marblestone AH, Boyden ES (2017) Feasibility of 3D Reconstruction of Neural Morphology Using Expansion Microscopy and Barcode-Guided Agglomeration, Frontiers in Computational Neuroscience 11:97.

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.