Instant Prior-Free Resolution Enhancement for Cross-Modality Microscopy

The resolving power of optical microscopy is fundamentally constrained by the diffraction of light, limiting our ability to visualize subcellular structures. Computational methods, particularly deconvolution, can restore blurred images but critically depend on an accurate point spread function (PSF), whose estimation is often impractical and error-prone, leading to artifacts. Here, we introduce Nonlinear Fourier Re-weighting (NFR), a rapid algorithm that operates without any prior knowledge of the imaging system, achieving deconvolution-like effects through a single logarithmic mapping of the images Fourier spectrum. This non-iterative process re-balances spatial frequency components to computationally reverse the effects of optical blurring. We demonstrate that NFR robustly enhances resolution beyond the Sparrow limit and recovers authentic structural details. NFR excels where traditional methods fail, remaining effective in the presence of severe optical aberrations and high noise. Furthermore, NFR synergistically improves the output of super-resolution modalities like structured illumination microscopy (SIM), and its near-instantaneous processing enables real-time enhancement of dynamic biological processes, such as in vivo multi-photon microscopic imaging deep within scattering tissue. By decoupling high-fidelity image restoration from system modeling, NFR offers a powerful, accessible, and universally applicable tool for improving image quality across diverse microscopic techniques, facilitating the analysis of large datasets and the discovery of previously obscured biological phenomena.