Noninvasive megapixel fluorescence microscopy through scattering layers by a virtual incoherent reflection matrix

Optical-resolution fluorescence imaging through and within complex samples presents a major challenge due to random light scattering, with substantial implications across multiple fields. While considerable advancements in coherent imaging through severe multiple scattering have been recently introduced by reflection matrix processing, approaches that tackle scattering in incoherent fluorescence imaging have been limited to sparse targets, require high-resolution control of the illumination or detection wavefronts, or require a very large number of measurements. Here, we present an approach that allows the adaptation of well-established reflection matrix techniques to scattering compensation in incoherent fluorescence imaging. We experimentally demonstrate that a small number of conventional wide-field fluorescence microscope images acquired under unknown random illuminations can effectively be used to construct a virtual fluorescence-based reflection matrix. Processing this matrix by an adapted matrix-based scattering compensation algorithm allows reconstructing megapixel-scale images from <150 acquired frames, without any spatial light modulators or computationally intensive processing.