Monodisperse versus polydisperse ultrasound contrast agents: nonlinear response, sensitivity, and deep tissue imaging potential

TL;DR

This study compares monodisperse and polydisperse microbubble ultrasound contrast agents, demonstrating that monodisperse agents have significantly higher sensitivity and nonlinear response, which can improve deep tissue imaging and localized therapy.

Contribution

The paper provides the first experimental comparison showing monodisperse microbubbles have up to 100 times greater sensitivity and can confine scattering to improve deep tissue imaging.

Findings

Monodisperse agents show up to two orders of magnitude increase in sensitivity.

Nonlinear response of sorted microbubbles can confine scattering to the focal region.

Potential for improved deep tissue imaging and localized therapy.

Abstract

Monodisperse microbubble ultrasound contrast agents have been proposed to further increase the signal-to-noise-ratio of contrast enhanced ultrasound imaging. Here, the sensitivity of a polydisperse preclinical agent was compared experimentally to that of its size- and acoustically-sorted derivatives by using narrowband pressure- and frequency-dependent scattering and attenuation measurements. The sorted monodisperse agents showed up to a two orders of magnitude increase in sensitivity, i.e. in the average scattering cross-section per bubble. Moreover, we demonstrate here, for the first time, that the highly nonlinear response of acoustically sorted microbubbles can be exploited to confine scattering and attenuation to the focal region of ultrasound fields used in clinical imaging. This property is a result of minimal prefocal scattering and attenuation and can be used to minimize shadowing effects in deep tissue imaging. Moreover, it potentially allows for more localized therapy using microbubbles through the spatial control of resonant microbubble oscillations.