The difference-frequency (DF) ultrasound generated by using parametric effect promises to improve detection depth owing to its low attenuation, which is beneficial for deep tissue imaging. With ultrasound contrast agents infusion, the harmonic components scattered from the microbubbles, including DF, can be generated due to the nonlinear vibration. A theoretical study on the DF generation from microbubbles under the dual-frequency excitation is proposed in formula based on the solution of the RPNNP equation. The optimisation of the DF generation is discussed associated with the applied acoustic pressure, frequency, and the microbubble size. Experiments are performed to validate the theoretical predictions by using a dual-frequency signal to excite microbubbles. Both the numerical and experimental results demonstrate that the optimised DF ultrasound can be achieved as the difference frequency is close to the resonance frequency of the microbubble and improve the contrast-to-tissue ratio in imaging.
