Nile Red derivatives enable improved ratiometric imaging for nerve-specific contrast

Area of Science:

• Biomedical Engineering
• Surgical Technology
• Optical Imaging

Background:

• Surgical nerve damage is a significant risk, leading to complications and reduced quality of life.
• Fluorescence-guided surgery (FGS) aims to improve tissue visualization, but lacks nerve-specific contrast agents.
• Existing nerve-targeting fluorophores often accumulate in adipose tissue, hindering specific nerve identification.

Purpose of the Study:

• To synthesize and screen a library of oxazine fluorophores based on the Nile Red scaffold.
• To identify a fluorophore with high adipose specificity and minimal nerve uptake for ratiometric imaging.
• To evaluate the selected fluorophore's performance in improving nerve contrast during fluorescence-guided surgery.

Main Methods:

• Synthesis of an oxazine fluorophore library derived from the Nile Red scaffold.
• Ex vivo and in vivo screening of fluorophores for tissue specificity (adipose, nerve, muscle).
• Ratiometric imaging to assess nerve-to-adipose contrast enhancement.

Main Results:

• A novel Nile Red derivative was identified with strong adipose specificity and negligible nerve uptake.
• The selected fluorophore significantly improved nerve contrast, particularly nerve-to-adipose contrast.
• Ratiometric imaging with the new fluorophore enhanced visualization compared to parent compound or nerve-specific imaging alone.

Conclusions:

• A novel adipose-specific Nile Red derivative was developed for fluorescence-guided surgery.
• This fluorophore enhances nerve-to-adipose contrast, addressing a key challenge in nerve identification.
• The compound shows potential for future FGS applications requiring specific adipose or nerve visualization.