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Highly Resolved Intravital Striped-illumination Microscopy of Germinal Centers

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Feature-driven whole-tissue imaging with subcellular resolution.

Jinlong Lin¹, Zach Marin², Xiaoding Wang¹

¹Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Cell Reports Methods

|September 3, 2025

Summary

This summary is machine-generated.

We developed multiscale cleared tissue axially swept light-sheet microscopy (MCT-ASLM) for high-resolution imaging of large intact tissues. This microscopy platform bridges subcellular and tissue scales to study complex biological events.

Keywords:

CP: Imaging LSFM cancer development feature-driven cleared tissue imaging multiscale ASLM neuroscience

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Area of Science:

Biomedical Engineering
Microscopy
Cell Biology

Background:

Current microscopy struggles to image rare biological events across large tissue volumes.
Limitations exist in achieving both high resolution and a cm-scale field of view simultaneously.

Purpose of the Study:

To introduce a novel microscopy platform, MCT-ASLM, for high-resolution imaging of intact tissues.
To enable the study of hierarchical organization and complex biological processes across multiple scales.

Main Methods:

Developed multiscale cleared tissue axially swept light-sheet microscopy (MCT-ASLM).
Platform combines cm-scale imaging with targeted high-resolution interrogation (down to ~300 nm).
Operates in human-guided or autonomous modes for flexible tissue analysis.

Main Results:

MCT-ASLM captures fields of view up to 21 mm at micron-scale resolution.
Seamless transition to targeted imaging mode with isotropic resolution approaching 300 nm.
Demonstrated applications in mapping neuronal circuits, visualizing kidney innervation, and examining tumor microenvironments.

Conclusions:

MCT-ASLM bridges subcellular- to tissue-level scales for comprehensive biological studies.
This versatile microscopy method facilitates understanding of local events within global biological phenomena.
Enables detailed investigation of spatially complex biological processes in intact tissues.