Interstitial Fluid Streaming in Deep Tissue Induced by Ultrasound Momentum Transfer for Accelerating Nanoagent Transport and Controlling Its Distribution

This study aims to theoretically investigate the dynamics of ultrasound-induced interstitial fluid streaming and tissue recovery after ultrasound exposure for potentially accelerating nanoagent transport and controlling its distribution in tissue.Starting from fundamental equations, the dynamics of ultrasound-induced interstitial fluid streaming and tissue relaxation after an ultrasound exposure were modeled, derived and simulated. Also, both ultrasound-induced mechanical and thermal effects were considered in the models.The proposed new mechanism was named squeezing interstitial fluid via transfer of ultrasound momentum (SIF-TUM). It means that an ultrasound beam can squeeze the tissue in a small focal volume from all the directions, and generate a macroscopic streaming of interstitial fluid and a compression of tissue solid matrix. After the ultrasound is turned off, the solid matrix will recover and can generate a backflow. Rather than the ultrasound pressure itself or intensity, the streaming velocity is determined by the dot product of the ultrasound pressure gradient and its conjugate. Tissue and nanoagent properties also affect the streaming and recovery velocities.The mobility of therapeutic or diagnostic agents, such as drugs, drug carriers, or imaging contrast agents, in the interstitial space of many diseased tissues, such as tumors, is usually extremely low because of the inefficiency of the natural transport mechanisms. Therefore, the interstitial space is one of the major barriers hindering agent deliveries. The ability to externally accelerate agent transport and control its distribution is highly desirable. Potentially, SIF-TUM can be a powerful technology to accelerate agent transport in deep tissue and control the distribution if appropriate parameters are selected.