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High-Throughput Volumetric Mapping Facilitated by Active Tissue SHRINK.

Li-En Lin1, Adrian Colazo1, Xiaotian Bi1

  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, 91125, USA.

Small Methods
|April 8, 2025
PubMed
Summary

Scalable Hydrogel-embedded Rapid Imaging of tissue NetworK (SHRINK) enables rapid, high-resolution imaging of large organs by shrinking tissue samples. This technique enhances imaging throughput and signal for detailed visualization of organ architecture.

Keywords:
fluorescence imaginghigh‐throughput imagingstimulated Raman scattering microscopytissue clearingtissue shrinkage

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Area of Science:

  • Biomedical imaging
  • Tissue engineering
  • Microscopy

Background:

  • Visualizing large organ architecture with subcellular resolution is challenging due to sample size.
  • Current methods require extensive imaging time, reconstruction, and compromise spatial coverage.

Purpose of the Study:

  • To develop a novel method for efficient, high-resolution imaging of entire organs.
  • To overcome limitations in imaging speed and signal-to-noise ratio for large-scale tissue mapping.

Main Methods:

  • Introduced Scalable Hydrogel-embedded Rapid Imaging of tissue NetworK (SHRINK) for active tissue shrinkage and clearing.
  • Utilized a hydrogel network to preserve protein spatial patterns and remove non-crosslinked biomolecules.
  • Applied SHRINK in conjunction with stimulated Raman scattering (SRS) microscopy.

Main Results:

  • SHRINK achieved isotropic sample size reduction to 16% of original volume, preserving tissue integrity.
  • Demonstrated a sixfold enhancement in imaging throughput and signal.
  • Successfully mapped organ-scale brain, intestine, heart, and kidney tissues using SHRINK-SRS.

Conclusions:

  • SHRINK provides a powerful approach to overcome traditional imaging barriers for large organs.
  • Enables rapid, detailed, and label-free 3D tissue mapping.
  • Facilitates comprehensive visualization of organ-scale functional relationships.