Pressure-Dependent Superharmonic Resonance of Lipid-Coated Bubbles Provides Key Insights into the Echogenicity of Submicron Agents

The nonlinear acoustic response of lipid-coated microbubbles (MBs) has been extensively employed in contrast-enhanced ultrasound applications. Although the harmonic and subharmonic behaviors of micron-sized MBs have been thoroughly studied, the acoustic response of commercially prevalent submicron contrast agents (<1 μm) remains poorly understood. Interestingly, several experimental studies reported significantly higher contrast from submicron bubbles than predicted by linear scattering, which scales with the sixth power of radius. This work aims to elucidate the underlying physical mechanisms driving the high echogenicity observed in submicron agents.