Unpaired data training enables super-resolution confocal microscopy from low-resolution acquisitions.

Supervised deep-learning models have enabled super-resolution imaging in several microscopic imaging modalities, increasing the spatial lateral bandwidth of the original input images beyond the diffraction limit. Despite their success, their practical application poses several challenges in terms of the amount of training data and its quality, requiring the experimental acquisition of large, paired databases to generate an accurate generalized model whose performance remains invariant to unseen data. Cycle-consistent generative adversarial networks (cycleGANs) are unsupervised models for image-to-image translation tasks that are trained on unpaired datasets. This paper introduces a cycleGAN framework specifically designed to increase the lateral resolution limit in confocal microscopy by training a cycleGAN model using low- and high-resolution unpaired confocal images of human glioblastoma cells. Training and testing performances of the cycleGAN model have been assessed by measuring specific metrics such as background standard deviation, peak-to-noise ratio, and a customized frequency content measure. Our cycleGAN model has been evaluated in terms of image fidelity and resolution improvement using a paired dataset, showing superior performance than other reported methods. This work highlights the efficacy and promise of cycleGAN models in tackling super-resolution microscopic imaging without paired training, paving the path for turning home-built low-resolution microscopic systems into low-cost super-resolution instruments by means of unsupervised deep learning.