Deep learning for high-throughput quantification of oligodendrocyte ensheathment at single-cell resolution

High-throughput quantification of oligodendrocyte myelination is a challenge that, if addressed, would facilitate the development of therapeutics to promote myelin protection and repair. Here, we established a high-throughput method to assess oligodendrocyte ensheathment in-vitro, combining nanofiber culture devices and automated imaging with a heuristic approach that informed the development of a deep learning analytic algorithm. The heuristic approach was developed by modeling general characteristics of oligodendrocyte ensheathments, while the deep learning neural network employed a UNet architecture and a single-cell training method to associate ensheathed segments with individual oligodendrocytes. Reliable extraction of multiple morphological parameters from individual cells, without heuristic approximations, allowed the UNet to match the accuracy of expert-human measurements. The capacity of this technology to perform multi-parametric analyses at the level of individual cells, while reducing manual labor and eliminating human variability, permits the detection of nuanced cellular differences to accelerate the discovery of new insights into oligodendrocyte physiology.