Theoretical predictions of harmonic generation from submicron ultrasound contrast agents for nonlinear biomedical ultrasound imaging

Submicron ultrasound contrast agents have aroused attention for their significant promise in ultrasonic contrast/molecular imaging, targeted therapy and echo particle imaging velocimetry. However, nonlinear acoustic properties of submicron encapsulated gas bubbles for ultrasonic applications are still not clearly understood. In this paper, nonlinear acoustic emission characteristics from submicron bubbles were examined using a numerical study. The modified RP equation incorporating viscosity, acoustic radiation, thermal effects and encapsulated shell was used to study single bubble dynamics. Further, a size integration method, shown previously to be useful in prediction of backscatter spectra from groups of bubbles, was applied to analyse response from a bubble population. We show that bubbles with radii (200-500 nm) produce significant subharmonic and ultraharmonic components of the backscatter spectrum, while smaller bubbles (<200 nm) provide substantial second harmonic components. Additionally, nanoscale bubbles (<100 nm) produce very low backscatter amplitudes and thus may not be useful with the use of current ultrasound technology. Analysing optimal ultrasound driving pressures and bubbles size ranges for maximal subharmonic and ultraharmonic signals showed that sub and ultraharmonic mode nonlinear imaging methods may be potentially competitive for larger size bubbles (>200 nm) in providing proper contrast-to-tissue signal ratios.