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To facilitate practical medical applications such as cancer treatment utilizing focused ultrasound and bubbles, a mathematical model that can describe the soft viscoelasticity of human body, the nonlinear propagation of focused ultrasound, and the nonlinear oscillations of multiple bubbles is theoretically derived and numerically solved. The Zener viscoelastic model and Keller–Miksis bubble equation, which have been used for analyses of single or few bubbles in viscoelastic liquid, are used to model the liquid containing multiple bubbles. From the theoretical analysis based on the perturbation expansion with the multiple-scales method, the Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation, which has been used as a mathematical model of weakly nonlinear propagation in single phase liquid, is extended to viscoelastic liquid containing multiple bubbles. The results show that liquid elasticity decreases the magnitudes of the nonlinearity, dissipation, and dispersion of ultrasound and increases the phase velocity of the ultrasound and linear natural frequency of the bubble oscillation. From the numerical calculation of resultant KZK equation, the spatial distribution of the liquid pressure fluctuation for the focused ultrasound is obtained for cases in which the liquid is water or liver tissue. In addition, frequency analysis is carried out using the fast Fourier transform, and the generation of higher harmonic components is compared for water and liver tissue. The elasticity suppresses the generation of higher harmonic components and promotes the remnant of the fundamental frequency components. This indicates that the elasticity of liquid suppresses shock wave formation in practical applications.

A physico-mathematical model composed of a single equation that consistently describes nonlinear focused ultrasound, bubble oscillations, and temperature fluctuations is theoretically proposed for microbubble-enhanced medical applications. The Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation that has been widely used as a simplified model for nonlinear propagation of focused ultrasound in pure liquid is extended to that in liquid containing many spherical microbubbles, by applying the method of multiple scales to the volumetric averaged basic equations for bubbly liquids. As a result, for two-dimensional and three-dimensional cases, KZK equations composed of the linear combination of nonlinear, dissipation, dispersion, and focusing terms are derived. Especially, the dissipation term depends on three factors, i.e., interfacial liquid viscosity, liquid compressibility, and thermal conductivity of gas inside bubbles; the thermal conduction is evaluated by using four types of temperature gradient models. Finally, we numerically solve the derived KZK equation and show a moderate temperature rise appropriate to medical applications.