Stress-strain analysis of single ultrasound-driven microbubbles for viscoelastic shell characterization

Microbubbles are of great interest both for ultrasound imaging and for ultrasound-assisted therapy due to their nonlinear scattering, which is enhanced by the viscoelastic shell. A full characterization of this nonlinear response is therefore crucial to fully exploit their potential. Current microbubble characterization techniques rely on assumptions regarding the microbubble shell rheology. Here, a stress-strain method is proposed to characterize the viscoelastic shells of single microbubbles with minimal underlying assumptions, which mainly entail separable viscous and elastic contributions. Detailed knowledge of the acoustic driving pressure and frequency, combined with a precise measurement of the bubble oscillations obtained through high-frequency ultrasound scattering, allows to derive the viscoelastic contribution of single microbubbles. To account for experimental uncertainties, we employed a fitting procedure of the surface tension in the buckled and ruptured regimes, which currently limits the applicability of the method to phospholipid-shelled microbubbles. The method was validated through simulations, and used to experimentally characterize 275 individual microbubbles from a monodisperse population, revealing a shell elasticity of (0.49 ± 0.10) N m-1, and initial surface tension of (28.7±3.94) mN m-1. Besides providing detailed information on single bubble dynamics, this analysis paves the way for the characterization of the viscous dissipation mechanisms of individual microbubble shells.