Effect of tissue viscoelasticity and adjacent phase-changed microbubbles on vaporization process and direct growth threshold of nanodroplet in an ultrasonic field.

Understanding the behavior of nanodroplets converted into microbubbles with applied ultrasound is an important problem in tumor therapeutical and diagnostic applications. In this study, a comprehensive model is proposed to investigate the vaporization process and the direct growth threshold of the nanodroplet by following the vapor bubble growth, especially attention devoted to the effect of tissue viscoelasticity and adjacent phase-changed microbubbles (PCMBs). It is shown that the ultrasonic energy must be sufficiently strong to counterbalance the natural condensation of the vapor bubble and the tissue stiffness-inhibitory effect. The softer tissue with a lower shear modulus favors the vaporization process, and the nanodroplet has a lower direct growth threshold in the softer tissue. Moreover, the adjacent PCMBs show a suppression effect on the vaporization process due to the negative value of the secondary Bjerknes force, implying an attractive force, preventing the nanodroplet from escaping from the constraint of the adjacent PCMBs. However, according to the linear scattering theory, the attractive force signifies that the constraint is weak, causing the direct growth threshold to increase in the range of 0.09-0.24 MPa. The weak increase in threshold demonstrates that the direct growth threshold is relatively unaffected by the adjacent PCMBs. The prediction results of our model are in good agreement with the experiment results obtained by the echo enhancement method, in which the threshold is relatively independent of the intermediate concentration. The findings presented here provide physical insight that will be further helpful in understanding the complex behavior of the nanodroplet responses to ultrasound in practical medical applications.