A stenographer is recording a meeting, but halfway through the conversation she runs out of paper. She misses a few lines, then picks up where she left off. Later, she needs to reconstruct the full transcript without rewriting the entire conversation from scratch. That's exactly how the new method URA-SIM works for structured illumination microscopy (SIM).

Previously, if there were fewer frames, reconstruction became unstable, and replacing the entire processing pipeline was risky. URA-SIM acts like an experienced translator: it doesn't retranslate the conversation but merely fills in the gaps in the transcript. The method estimates the missing phase images based on a low-dimensional harmonic model — the very brightness oscillations created by the striped light. It then passes the complete set of frames to a proven reconstruction pipeline.

On the Argolight calibration target and biological samples (microtubules, mitochondria), reconstructions from 5–8 frames maintain a resolution of 120 nanometers and show no artifacts. For microtubules, image quality improves from 27.05 decibels with 5 frames to 33.00 decibels with 8 frames. On living COS7 cells with mitochondria labeled with Pkmito Orange, URA-SIM with 5–8 frames outperforms Bayesian and frequency-domain methods in visual similarity to full-frame reconstruction.

In experiments with a fixed 5 frames per super-resolution image, the method resolves mitochondrial cristae at 20-second intervals, 1-second intervals, and in a series of 1461 frames. Transfer to 3D-SIM with 11–14 frames out of 15 yields quality up to 49.07 decibels; on nonlinear SIM with 15–24 frames out of 25, similarity increases from 0.9054 to 0.9954.

The stenographer, after filling in the missing lines, hands in the complete transcript. Similarly, URA-SIM returns a full stack of frames, which is then processed by classical algorithms. This preserves calibration, optical transfer function processing, and other developments of classical SIM. Already today, the method can be used for accelerated imaging of living cells with reduced phototoxicity, especially for observing mitochondrial dynamics.