ScaleS: an optical clearing palette for biological imaging

Area of Science:

• Neuroscience
• Biomedical Imaging
• Biochemistry

Background:

• Optical clearing is crucial for deep biological imaging, but current methods can damage tissue structure and compromise signal stability.
• Preserving tissue integrity is essential for accurate 3D reconstruction and reliable analysis in multi-scale high-resolution imaging.

Purpose of the Study:

• To develop a novel optical clearing method that ensures stable tissue preservation for immunochemical labeling and 3D signal rendering.
• To evaluate the efficacy of the new method in visualizing aged and diseased brain tissue, particularly in Alzheimer's disease models.

Main Methods:

• Development of ScaleS, a sorbitol-based optical clearing agent.
• Application of ScaleS for optical reconstructions of Alzheimer's disease model brains.
• Multi-scale imaging using successive fluorescence and electron microscopy.
• Analysis of human Alzheimer's disease clinical samples using reversible optical re-sectioning.

Main Results:

• ScaleS demonstrated stable tissue preservation, enabling accurate 3D reconstruction of anatomical structures and fluorescence signals.
• The method allowed detailed mapping of amyloid plaques, neurons, and microglia in Alzheimer's disease models.
• ScaleS exhibited superior signal and structure preservation compared to contemporary clearing agents in benchmarking studies.
• Analysis of human samples revealed insights into plaque pathogenesis in the z-axis.

Conclusions:

• ScaleS is a simple, reproducible optical clearing method that enhances tissue preservation for high-resolution 3D imaging.
• This technique facilitates accurate visualization of biological tissues, particularly for studying neurodegenerative diseases like Alzheimer's.
• ScaleS offers a significant advancement for reproducible anatomical and fluorescence signal stability in deep biological imaging.