Ultrasound-modulated fluorescence based on donor-acceptor-labeled microbubbles

Area of Science:

• Biomedical Optics
• Acoustic Imaging
• Nanotechnology

Background:

• Fluorescence resonance energy transfer (FRET) is a technique used to measure molecular proximity.
• Ultrasound-modulated fluorescence (UMF) offers a potential method for deep-tissue optical imaging.
• Microbubbles are established contrast agents for ultrasound imaging.

Purpose of the Study:

• To design and experimentally validate a FRET-based microbubble contrast agent system for demonstrating ultrasound-modulated fluorescence (UMF).
• To investigate the feasibility of using dual-fluorophore-labeled microbubbles for UMF imaging.

Main Methods:

• Microbubbles were surface-labeled with both donor and acceptor fluorophores to optimize FRET efficiency.
• Ultrasound was applied to induce microbubble size oscillations, altering the distance between fluorophores.
• Fluorescence changes in response to ultrasound were measured at the single-microbubble and solution levels.

Main Results:

• Simultaneous labeling of microbubbles with donor and acceptor fluorophores effectively minimized self-quenching and maximized FRET.
• Ultrasound-induced microbubble size oscillations significantly modulated FRET efficiency by altering fluorophore proximity.
• Both donor and acceptor fluorophores exhibited UMF, with the donor showing a more pronounced effect.
• UMF signal from the donor was successfully detected in a microbubble solution within turbid media.

Conclusions:

• Donor–acceptor labeled microbubbles represent a feasible and promising contrast agent system for ultrasound-modulated fluorescence imaging.
• The developed system effectively demonstrates the principle of UMF by leveraging ultrasound-triggered microbubble dynamics.
• This approach holds potential for enhancing contrast and enabling targeted imaging in complex biological environments.