Volumetric imaging by fluorescence microscopy is often limited by anisotropic spatial resolution from inferior axial resolution compared to the lateral resolution. To address this problem, here we present a deep-learning-enabled unsupervised super-resolution technique that enhances anisotropic images in volumetric fluorescence microscopy. In contrast to the existing deep learning approaches that require matched high-resolution target volume images, our method greatly reduces the effort to put into practice as the training of a network requires as little as a single 3D image stack, without a priori knowledge of the image formation process, registration of training data, or separate acquisition of target data. This is achieved based on the optimal transport driven cycle-consistent generative adversarial network that learns from an unpaired matching between high-resolution 2D images in lateral image plane and low-resolution 2D images in the other planes. Using fluorescence confocal microscopy and light-sheet microscopy, we demonstrate that the trained network not only enhances axial resolution, but also restores suppressed visual details between the imaging planes and removes imaging artifacts.
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