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Updated: May 21, 2025

Mesoscopic Optical Imaging of Whole Mouse Heart

Mesoscopic Optical Imaging of Whole Mouse Heart

Published on: October 14, 2021

Nonlinear sound-sheet microscopy: Imaging opaque organs at the capillary and cellular scale.

Baptiste Heiles¹, Flora Nelissen², Rick Waasdorp¹

¹Department of Imaging Physics, Delft University of Technology, Delft, Netherlands.

Science (New York, N.Y.)

|April 3, 2025

Summary

Nonlinear sound-sheet microscopy enables fast, volumetric imaging of biological functions in large tissue volumes. This advanced technique overcomes limitations of light-sheet microscopy for studying complex biological processes deep within specimens.

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Area of Science:

Biomedical imaging
Acoustic microscopy
Molecular imaging

Background:

Light-sheet fluorescence microscopy is limited by light scattering and photobleaching in thick tissues.
Studying dynamic cellular processes in vivo often requires imaging beyond the penetration depth of light.

Purpose of the Study:

To develop a novel imaging method for fast and volumetric visualization of biological functions in centimeter-scale volumes.
To overcome the limitations of optical microscopy in scattering and opaque biological tissues.

Main Methods:

Application of nondiffractive ultrasound beams with a cross-amplitude modulation sequence.
Utilizing nonlinear acoustic reporters, including genetically encoded gas vesicles and intravascular microbubbles.
Development of nonlinear sound-sheet microscopy for accelerated imaging.

Main Results:

Achieved volumetric imaging of tumor gene expression at the cubic centimeter scale.
Enabled localization microscopy of cerebral capillary networks using microbubble contrast agents.
Demonstrated ~64x acceleration in imaging speed, ~35x increase in imaged volume, and ~4x resolution improvement.

Conclusions:

Nonlinear sound-sheet microscopy offers a significant advancement for deep-tissue biological imaging.
The technique enables high-speed, volumetric functional imaging at unprecedented scales.
This method expands the possibilities for studying complex biological processes in vivo.