Color-neutral and reversible tissue transparency enables longitudinal deep-tissue imaging in live mice

Area of Science:

• Biomedical Optics
• In Vivo Imaging
• Tissue Engineering

Background:

• Light scattering in biological tissues impedes deep in vivo optical imaging.
• Previous methods achieved red spectrum transparency but were limited.
• A need exists for broader spectrum optical transparency in live tissues.

Purpose of the Study:

• To develop a color-neutral method for achieving optical transparency across the visible spectrum.
• To enable deep tissue imaging of commonly used fluorophores.
• To facilitate longitudinal imaging of the live mouse brain.

Main Methods:

• Utilized molecules with strong ultraviolet absorption and sharp edges into the visible spectrum.
• Administered these molecules to live mice to induce reversible tissue transparency.
• Performed structural and functional imaging of the mouse brain through intact scalp and skull.

Main Results:

• Achieved optical transparency across the entire visible spectrum, including green and yellow wavelengths.
• Enabled clear imaging of yellow fluorescent protein and GCaMP in the mouse brain.
• Demonstrated longitudinal imaging of the same brain regions over multiple days in awake mice.
• Histological and toxicology studies showed minimal skin or systemic damage.

Conclusions:

• The color-neutral, reversible tissue transparency method significantly advances noninvasive deep-tissue optical imaging.
• This technique allows for long-term visualization of cellular structures and dynamic activity.
• Opens new avenues for high spatiotemporal resolution chronic tracking in vivo.