Coordinate-based neural representations for computational adaptive optics in widefield microscopy

Widefield microscopy is widely used for non-invasive imaging of biological structures at subcellular resolution. When applied to a complex specimen, its image quality is degraded by sample-induced optical aberration. Adaptive optics can correct wavefront distortion and restore diffraction-limited resolution but require wavefront sensing and corrective devices, increasing system complexity and cost. Here we describe a self-supervised machine learning algorithm, CoCoA, that performs joint wavefront estimation and three-dimensional structural information extraction from a single-input three-dimensional image stack without the need for external training datasets. We implemented CoCoA for widefield imaging of mouse brain tissues and validated its performance with direct-wavefront-sensing-based adaptive optics. Importantly, we systematically explored and quantitatively characterized the limiting factors of CoCoA’s performance. Using CoCoA, we demonstrated in vivo widefield mouse brain imaging using machine learning-based adaptive optics. Incorporating coordinate-based neural representations and a forward physics model, the self-supervised scheme of CoCoA should be applicable to microscopy modalities in general. Adaptive optics (AO) corrects aberrations and restores resolution but requires specialized hardware. Kang et al. introduce a self-supervised AO method (CoCoA) for widefield microscopy, achieving in vivo mouse brain imaging without wavefront sensors.