Size-Selected Microbubbles for Superharmonic Contrast Imaging

The nonlinear behavior of microbubbles (MBs) is dependent on both the excitation pressure and the MB properties, which rely on the composition of the gas core and shell, as well as the size. Polydisperse MBs have a broad size distribution and only a subpopulation of them may be contributing to the higher order harmonics that are used for superharmonic imaging. High MB concentrations have been used for superharmonic imaging to produce nonlinear responses from the polydisperse MB solution for good image contrast. In this work, we investigate in vitro the contrast signal intensity and longivity with in-house polydisperse MBs and size-selected MBs of ~1.5, 2.2, and 4.3 µm in diameter, comparing to commonly used MicroMarker MB solutions. We found the in-house 2.2 µm MBs showed comparable mean contrast intensities and signal decay to MicroMarker. We evaluated these two populations in vivo on mouse kidneys over an approximately 18-minute imaging duration, and assessed quantitatively the contrast intensities and longevity of superharmonic signals. We found MicroMarker showed greater superharmonic contrast over the entire acquisition in vivo, with a half-life almost twice to that of the in-house 2.2 µm MBs.