Doppler Passive Acoustic Mapping.

In therapeutic ultrasound using microbubbles, it is essential to drive the microbubbles into the correct type of activity and the correct location to produce the desired biological response. Although passive acoustic mapping (PAM) is capable of locating where microbubble activities are generated, it is well known that microbubbles rapidly move within the ultrasound beam. We propose a technique that can image microbubble movement by estimating their velocities within the focal volume. Microbubbles embedded within a wall-less channel of a tissue-mimicking material were sonicated using 1-MHz focused ultrasound. The acoustic emissions generated by the microbubbles were captured with a linear array (L7-4). PAM with robust Capon beamforming was used to localize the microbubble acoustic emissions. We spectrally analyzed the time trace of each position and isolated the higher harmonics. Microbubble velocity maps were constructed from the position-dependent Doppler shifts at different time points during sonication. Microbubbles moved primarily away from the transducer at velocities on the order of 1 m/s due to primary acoustic radiation forces, producing a time-dependent velocity distribution. We detected microbubble motion both away and toward the receiving array, revealing the influence of acoustic radiation forces and fluid motion due to the ultrasound exposure. High-speed optical images confirmed the acoustically measured microbubble velocities. Doppler PAM enables passive estimation of microbubble motion and may be useful in therapeutic applications, such as drug delivery across the blood-brain barrier, sonoporation, sonothrombolysis, and drug release.

Acoustic Streaming in a Soft Tissue Microenvironment.

We demonstrated that sound can push fluid through a tissue-mimicking material. Although acoustic streaming in tissue has been proposed as a mechanism for biomedical ultrasound applications, such as neuromodulation and enhanced drug penetration, streaming in tissue or acoustic phantoms has not been directly observed. We developed a material that mimics the porous structure of tissue and used a dye and a video camera to track fluid movement. When applied above an acoustic intensity threshold, a continuous focused ultrasound beam (spatial peak time average intensity: 238 W/cm2, centre frequency: 5 MHz) was found to push the dye axially, that is, in the direction of wave propagation and in the radial direction. Dye clearance increased with ultrasound intensity and was modelled using an adapted version of Eckart's acoustic streaming velocity equation. No microstructural changes were observed in the sonicated region when assessed using scanning electron microscopy. Our study indicates that acoustic streaming can occur in soft porous materials and provides a mechanistic basis for future use of streaming for therapeutic or diagnostic purposes.

Acoustic particle palpation for measuring tissue elasticity.

We propose acoustic particle palpation-the use of sound to press a population of acoustic particles against an interface-as a method for measuring the qualitative and quantitative mechanical properties of materials. We tested the feasibility of this method by emitting ultrasound pulses across a tunnel of an elastic material filled with microbubbles. Ultrasound stimulated the microbubble cloud to move in the direction of wave propagation, press against the distal surface, and cause deformations relevant for elasticity measurements. Shear waves propagated away from the palpation site with a velocity that was used to estimate the material's Young's modulus.