Artefact removal in ground truth deficient fluctuations-based nanoscopy images using deep learning

Image denoising or artefact removal using deep learning is possible in the availability of supervised training dataset acquired in real experiments or synthesized using known noise models. Neither of the conditions can be fulfilled for nanoscopy (super-resolution optical microscopy) images that are generated from microscopy videos through statistical analysis techniques. Due to several physical constraints, a supervised dataset cannot be measured. Further, the non-linear spatio-temporal mixing of data and valuable statistics of fluctuations from fluorescent molecules that compete with noise statistics. Therefore, noise or artefact models in nanoscopy images cannot be explicitly learned. Here, we propose a robust and versatile simulation-supervised training approach of deep learning auto-encoder architectures for the highly challenging nanoscopy images of sub-cellular structures inside biological samples. We show the proof of concept for one nanoscopy method and investigate the scope of generalizability across structures, and nanoscopy algorithms not included during simulation-supervised training. We also investigate a variety of loss functions and learning models and discuss the limitation of existing performance metrics for nanoscopy images. We generate valuable insights for this highly challenging and unsolved problem in nanoscopy, and set the foundation for the application of deep learning problems in nanoscopy for life sciences.