Reflection from bound microbubbles at high ultrasound frequencies.

Targeted contrast agents and ultrasound imaging are now used in combination for the assessment and tracking of biomarkers in animal models in vivo. These applications have triggered interest in the understanding and prediction of the ultrasound echoes from contrast agents attached to cells. This study describes the reflection enhancement due to microbubbles bound on a gelatin surface. The reflection enhancement was measured using ultrasound pulses at high frequency (40 MHz) and low pressure (38 kPa peak-negativepressure) allowing a linear approximation to be applied. The observed reflection coefficient increased with the number of microbubbles, until reaching saturation at 0.9 when the surface coverage fraction was 35%. A multiple scattering model assuming that the targeted microbubbles are confined within an infinitesimally thin layer appeared suitable in predicting the reflection coefficient even at very high surface densities. These results could permit the optimization of the sensitivity of highfrequency ultrasound to targeted contrast agents.