Coordinate-conditioned Deconvolution for Scalable Spatially Varying High-Throughput Imaging

Wide-field fluorescence microscopy with compact optics often suffers from spatially varying blur due to field-dependent aberrations, vignetting, and sensor truncation, while finite sensor sampling imposes an inherent trade-off between field of view (FOV) and resolution. Computational Miniaturized Mesoscope (CM2) alleviate the sampling limit by multiplexing multiple sub-views onto a single sensor, but introduce view crosstalk and a highly ill-conditioned inverse problem compounded by spatially variant point spread functions (PSFs). Prior learning-based spatially varying (SV) reconstruction methods typically rely on global SV operators with fixed input sizes, resulting in memory and training costs that scale poorly with image dimensions. We propose SV-CoDe (Spatially Varying Coordinate-conditioned Deconvolution), a scalable deep learning framework that achieves uniform, high-resolution reconstruction across a 6.5 mm FOV. Unlike conventional methods, SV-CoDe employs coordinate-conditioned convolutions to locally adapt reconstruction kernels; this enables patch-based training that decouples parameter count from FOV size. SV-CoDe achieves the best image quality in both simulated and experimental measurements while requiring 10x less model size and 10x less training data than prior baselines. Trained purely on physics-based simulations, the network robustly generalizes to bead phantoms, weakly scattering brain slices, and freely moving C. elegans. SV-CoDe offers a scalable, physics-aware solution for correcting SV blur in compact optical systems and is readily extendable to a broad range of biomedical imaging applications.