Fast, efficient, and accurate neuro-imaging denoising via supervised deep learning.

Volumetric functional imaging is widely used for recording neuron activities in vivo, but there exist tradeoffs between the quality of the extracted calcium traces, imaging speed, and laser power. While deep-learning methods have recently been applied to denoise images, their applications to downstream analyses, such as recovering high-SNR calcium traces, have been limited. Further, these methods require temporally-sequential pre-registered data acquired at ultrafast rates. Here, we demonstrate a supervised deep-denoising method to circumvent these tradeoffs for several applications, including whole-brain imaging, large-field-of-view imaging in freely moving animals, and recovering complex neurite structures in C. elegans. Our framework has 30× smaller memory footprint, and is fast in training and inference (50-70 ms); it is highly accurate and generalizable, and further, trained with only small, non-temporally-sequential, independently-acquired training datasets (∼500 pairs of images). We envision that the framework will enable faster and long-term imaging experiments necessary to study neuronal mechanisms of many behaviors.