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. Fluorescence microscopy images that have been distorted by scattering are computationally corrected by a matrix-based approach.

Optical imaging through scattering media is important in a variety of fields ranging from microscopy to autonomous vehicles. Although advanced wavefront shaping techniques have offered several breakthroughs in the past decade, current techniques still require a known guide star and a high-resolution spatial light modulator or a very large number of measurements and are limited in their correction field of view. Here we introduce a guide-star-free, non-invasive approach that can correct more than 190,000 scattered modes using only 25 incoherently compounded, holographically measured, scattered light fields, obtained under unknown random illuminations. This is achieved by computationally emulating an image-guided wavefront shaping experiment, where several virtual spatial light modulators are simultaneously optimized to maximize the reconstructed image quality. Our method shifts the burden from the physical hardware to a digital, naturally parallelizable computational optimization, leveraging state-of-the-art automatic differentiation tools. We demonstrate the flexibility and generality of this framework by applying it to imaging through various complex samples and imaging modalities, including epi-illumination, anisoplanatic multi-conjugate correction of highly scattering layers, lensless endoscopy in multicore fibres and acousto-optic tomography. The presented approach offers high versatility, effectiveness and generality for fast, non-invasive imaging in diverse applications.

Imaging inside scattering media at optical resolution is a longstanding challenge affecting multiple fields, from bio-medicine to astronomy. In recent years, several groundbreaking techniques for imaging inside scattering media, in particular scattering-matrix-based approaches, have shown great promise. However, due to their reliance on the optical “memory-effect,” these techniques usually suffer from a restricted field of view. Here, we demonstrate that diffraction-limited imaging beyond the optical memory-effect can be robustly achieved by combining acousto-optic spatial-gating with state-of-the-art matrix-based imaging techniques. In particular, we show that this can be achieved by computational processing of scattered light fields captured under scanned acousto-optic modulation. The approach can be directly utilized whenever the ultrasound focus size is of the order of the memory-effect range, independently of the scattering angle.