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Diffusion prior-based zero-shot denoising for real-world fluorescence microscopy images via encoder-decoder guided

Qinxuan Luo1,2, Ziwen Liu1, Ge Yang1,2

  • 1School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China.

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|January 14, 2026
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Summary
This summary is machine-generated.

This study introduces ED-Diff, a novel zero-shot denoising algorithm for fluorescence microscopy images. It effectively removes noise without needing paired noisy-clean images, improving image quality for biological research.

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Area of Science:

  • Microscopy and Imaging
  • Computational Biology
  • Image Processing

Background:

  • Fluorescence microscopy is crucial for biological research but often yields noisy images due to technical constraints.
  • Existing denoising methods struggle with the unique noise characteristics of fluorescence microscopy and the difficulty of obtaining paired noisy-clean training data.

Purpose of the Study:

  • To develop a robust zero-shot denoising algorithm for fluorescence microscopy images that overcomes limitations of current methods.
  • To address the challenge of real-world noise in fluorescence microscopy without requiring paired training data.

Main Methods:

  • Proposes ED-Diff, a zero-shot denoising algorithm leveraging diffusion priors.
  • Integrates inverse problem optimization with diffusion sampling.
  • Introduces a novel noisy image transformation module (NiTM) with an encoder-decoder structure to handle diverse real-world noise.

Main Results:

  • Extensive experiments on multiple real-world datasets demonstrate the effectiveness of the NiTM module.
  • ED-Diff shows competitive and robust denoising performance across various noise scenarios.
  • Validated the algorithm's ability to denoise images without paired noisy-clean data.

Conclusions:

  • ED-Diff offers a significant advancement in denoising fluorescence microscopy images, particularly in real-world applications.
  • The proposed NiTM module enhances the algorithm's adaptability to complex noise patterns.
  • This method provides a practical solution for improving image quality in biological research where clean training data is scarce.