High-speed blind structured illumination microscopy via unsupervised algorithm unrolling

Blind structured illumination microscopy (blind-SIM) is a valuable tool for achieving super-resolution without the need for known illumination patterns. However, in its current formulation the algorithm requires many iterations to converge, leading to long inference times and limited use for real-time or video-rate imaging. We present unrolled blind-SIM (UBSIM), an algorithm which integrates a learnable neural network inside the unrolled iterations of the blind-SIM algorithm. UBSIM delivers a reconstruction speed two to three orders of magnitude faster than that of current iterative blind-SIM methods, while achieving similar resolution and image quality. Furthermore, we demonstrate that UBSIM can be trained in an unsupervised manner that reduces hallucinations and produces superior generalization capability when compared to benchmark super-resolution networks. We test UBSIM experimentally on live cells and present video-rate super-resolution imaging up to 50 Hz. Using our method, we observe dynamic remodeling of the endoplasmic reticulum with high spatiotemporal resolution.

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Publication Details

Journal
Nature Communications
Published
2026-01-23
DOI
https://doi.org/10.1038/s41467-026-68693-w
Primary Topic
Advanced Fluorescence Microscopy Techniques
Type
article
Field-Weighted Citation Impact
0.00

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article

High-speed blind structured illumination microscopy via unsupervised algorithm unrolling

Zachary Burns, Ayse Z. Sahan, Junxiang Zhao, Zhaowei Liu et al.
Nature Communications
Advanced Fluorescence Microscopy Techniques
article

High-speed blind structured illumination microscopy via unsupervised algorithm unrolling

Zachary Burns, Ayse Z. Sahan, Junxiang Zhao, Zhaowei Liu, Jin Zhang
article en

Abstract

Blind structured illumination microscopy (blind-SIM) is a valuable tool for achieving super-resolution without the need for known illumination patterns. However, in its current formulation the algorithm requires many iterations to converge, leading to long inference times and limited use for real-time or video-rate imaging. We present unrolled blind-SIM (UBSIM), an algorithm which integrates a learnable neural network inside the unrolled iterations of the blind-SIM algorithm. UBSIM delivers a reconstruction speed two to three orders of magnitude faster than that of current iterative blind-SIM methods, while achieving similar resolution and image quality. Furthermore, we demonstrate that UBSIM can be trained in an unsupervised manner that reduces hallucinations and produces superior generalization capability when compared to benchmark super-resolution networks. We test UBSIM experimentally on live cells and present video-rate super-resolution imaging up to 50 Hz. Using our method, we observe dynamic remodeling of the endoplasmic reticulum with high spatiotemporal resolution.

Nature CommunicationsVol. 17(1)
University of California San Diego (US)
National Science Foundation, National Institutes of Health, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Openalex Percentile: Top 82%
Advanced Fluorescence Microscopy Techniques
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