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Depth-Variant Deconvolution Applied to Widefield Microscopy for Rapid Large-Volume Tissue Imaging
Daniel Lee1, Kevin Telfer1, Mark Koenis2
1Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
Research Square
|June 12, 2025
Summary
This study introduces a fast, accessible 3D tissue imaging method using widefield microscopy and deconvolution. It achieves subnuclear resolution in thick tissues, enabling detailed pathological evaluation and research insights.
Area of Science:
- Biomedical Imaging
- Microscopy
- Pathology
Background:
- 3D tissue imaging is crucial but limited by protocol length and equipment access.
- Widefield microscopy offers speed and accessibility but lacks optical sectioning for 3D workflows.
Purpose of the Study:
- To develop an accessible 3D widefield microscopy method with subnuclear axial resolution.
- To overcome limitations of traditional 3D imaging techniques.
Main Methods:
- Combined tissue clearing with depth-variant deconvolution for large-volume widefield imaging.
- Applied the method to ileitis, cerebral amyloid angiopathy, and human kidney biopsies.
Main Results:
- Achieved subnuclear axial resolution up to 500 µm depth.
- Resolved amyloid deposits in brain vasculature, comparable to confocal microscopy.
- Enabled rapid 3D visualization of kidney biopsy microvasculature for pathological evaluation.
Conclusions:
- Widefield microscopy with deconvolution provides an accessible and viable method for 3D tissue imaging.
- This approach enhances research and clinical pathological evaluations.
- Facilitates rapid assessment of tissue structures in thick sections.

