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Label-free, multi-scale imaging of ex-vivo mouse brain using spatial light interference microscopy.

Eunjung Min1,2, Mikhail E Kandel1, CheMyong J Ko3

  • 1Quantitative Light imaging Laboratory, Department of Electrical and Computer Engineering, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N. Matthews Avenue, Urbana, IL 61801, USA.

Scientific Reports
|December 24, 2016
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Summary

Spatial light interference microscopy visualizes brain structure with high resolution and sub-nanometer sensitivity. This label-free technique reveals detailed neural architecture across multiple scales without exogenous contrast agents.

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Area of Science:

  • Neuroscience
  • Biophysics
  • Optical Microscopy

Background:

  • Brain connectivity spans diverse spatial scales, necessitating multiscale imaging approaches.
  • Current light microscopy techniques often require staining or fluorescent tags, limiting cytoarchitecture delineation and contrast.
  • Understanding brain structure at multiple scales is crucial for comprehending neural network function.

Purpose of the Study:

  • To investigate brain structure with high resolution and sub-nanometer sensitivity using spatial light interference microscopy (SLIM).
  • To overcome limitations of conventional microscopy, such as the need for exogenous contrast agents.
  • To demonstrate the capability of SLIM for multiscale and multicontrast imaging of neural tissue.

Main Methods:

  • Utilized spatial light interference microscopy (SLIM) for label-free, high-resolution imaging of brain tissue.
  • Developed and applied an in-house mosaic algorithm for wide-field imaging reconstruction.
  • Mapped tissue scattering properties to enhance contrast of anatomical structures and differentiate neural components.

Main Results:

  • Achieved detailed visualization of cellular and myelin architecture in coronal and sagittal brain sections (olfactory bulb, cortex, hippocampus, cerebellum).
  • Successfully identified laminar characteristics of fiber tract orientation in white matter, such as the corpus callosum.
  • Demonstrated improved macro-scale contrast and differentiation of axons, dendrites, and cell bodies through scattering property mapping.

Conclusions:

  • Spatial light interference microscopy offers a powerful label-free approach for high-resolution, multiscale brain imaging.
  • SLIM provides sub-nanometer pathlength sensitivity, enabling detailed cytoarchitectural analysis without contrast agents.
  • This technique holds potential for advancing our understanding of gross and microscopic brain anatomy across multiple contrasts.