Nonlinear resonance behavior and linear shell estimates for Definity™ and MicroMarker™ assessed with acoustic...

Area of Science:

• Acoustics
• Biomedical Engineering
• Materials Science

Background:

• Microbubble ultrasound contrast agents are crucial for diagnostic imaging.
• Understanding microbubble shell properties is key to optimizing imaging performance.
• Previous studies often analyze bubble populations, not individual bubble responses.

Purpose of the Study:

• To characterize the acoustic response and shell properties of individual microbubbles.
• To compare the nonlinear behavior and rheological properties of Target-Ready MicroMarker and Definity.
• To determine resonant frequencies and material properties for microbubbles in the 5-15 MHz range.

Main Methods:

• Individual microbubbles were insonified using acoustic spectroscopy with tone bursts (4-13.5 MHz).
• Radial excursion amplitude was calculated from scattered signals to generate resonance curves.
• Shell elasticity, viscosity, and rheological behavior were estimated from linear and asymmetric resonance curves.

Main Results:

• 69% of Target-Ready MicroMarker (2.5-4 μm) showed asymmetric resonance (nonlinear behavior), compared to 8% for Definity (1.7-3.1 μm).
• Target-Ready MicroMarker exhibited a stiffer shell (3-5 N/m) and distinct rheological behavior (strain-softening, shear-thinning) than Definity (0.5-2.5 N/m).
• Resonant frequencies differed, with Target-Ready MicroMarker resonant between 10-12 MHz (2.7-3.3 μm) and Definity between 1.7-2.6 μm.

Conclusions:

• Individual microbubble acoustic spectroscopy reveals distinct nonlinear behaviors and shell properties between Target-Ready MicroMarker and Definity.
• Target-Ready MicroMarker's stiffer shell and nonlinear response suggest different applications compared to Definity's more linear behavior.
• These findings aid in selecting appropriate microbubble agents for specific ultrasound imaging applications.