  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.
