A model for a lipid-coated microbubble based on transient network theory

Encapsulated microbubbles (EMBs) are widely used to enhance contrast in ultrasound sonography and are increasingly applied in biomedical therapies, such as drug/gene delivery and tissue ablation. EMBs consist of a gas core enclosed by a stabilizing shell made of various materials, including polymers, lipids, and proteins. Lipid-coated EMBs are challenging to model due to their large oscillations and nonlinear, viscoelastic properties. We propose a lipid-coated, spherical EMB model that simulates the encapsulating material using a statistically based continuum theory based on transient networks. The use of transient network theory enables local calculation of the viscoelastic properties of the encapsulation, including stress, elastic energy, and entropy, based on lipid-molecular configurations. The model depends on five physically grounded parameters: optimum lipid area, maximum bonds per lipid, buckling radius, and lipid association and dissociation rates. The model accurately replicates the experimentally measured natural frequency and radial response of ultrasonically driven, lipid-coated microbubbles. It also captures experimentally observed nonlinear responses, such as "compression-dominated" and "expansion-dominated " behavior, and provides a mechanistic explanation in terms of lipid bond kinetics. Furthermore, the model can be readily extended to nonspherical EMB deformations, which are essential in many biomedical applications.