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System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant

Jiashu Han1,2, Kunzan Liu1,2, Keith B Isaacson3

  • 1Research Laboratory of Electronics, MIT, Cambridge, MA, USA.

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|January 17, 2025
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Summary

This study introduces SSAI-3D, a novel framework for robust 3D imaging that overcomes optical microscopy limitations. It enhances axial resolution in label-free imaging of complex biological tissues, improving structural analysis.

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Area of Science:

  • Biomedical Imaging
  • Microscopy
  • Computational Biology

Background:

  • Optical microscopy's diffraction limit restricts axial resolution in 3D imaging.
  • Accurate 3D structural analysis is hindered, especially in label-free imaging of thick, heterogeneous tissues.
  • Standard imaging assumptions often fail for complex biological samples.

Purpose of the Study:

  • To develop a robust framework for isotropic 3D imaging.
  • To overcome limitations in axial resolution for label-free imaging of biological tissues.
  • To enable accurate 3D structural analysis in challenging samples.

Main Methods:

  • Introduced SSAI-3D, a weakly physics-informed, domain-shift-resistant framework.
  • Generated a diverse, noise-resilient, sample-informed training dataset.
  • Sparsely fine-tuned a large pre-trained blind deblurring network for axial deblurring.

Main Results:

  • SSAI-3D demonstrated robust axial deblurring capabilities.
  • The framework was successfully applied to label-free nonlinear imaging of organoids, human endometrium, and mouse whisker pads.
  • Validated on public datasets of 3D heterogeneous biological tissues with unknown imaging conditions.

Conclusions:

  • SSAI-3D provides a robust solution for isotropic 3D imaging.
  • The framework enhances axial resolution in challenging label-free microscopy applications.
  • Enables more accurate 3D structural analysis of complex biological tissues.