Flow estimation using subharmonics of microbubbles

It has been observed that the subharmonic signal of the microbubbles has a significant contrast-to-tissue ratio. The flow velocity can be evaluated precisely even without wall filter for subharmonics since the vessels containing the microbubbles would be distinguishable from the surrounding tissues. However, the microbubble cannot generate the subharmonics unless the applied pressure exceeds the required onset threshold. Moreover, it will undergo cavitation if the acoustic pressure is over the cavitation threshold. While the microbubble moves through the sample volume, there are three different regions inside the excitation beam. The beam-weighted pressure is below the onset threshold, between the onset and cavitation thresholds, and over the cavitation threshold. Since the subharmonics can occur only when the beam-weighted pressure is between the onset and cavitation thresholds, the observation time for subharmonics is shorter than that for the fundamental. Our numerical results showed that the onset threshold is very close to the cavitation threshold. Moreover, some microbubbles are found to generate subharmonics and undergo cavitation simultaneously. Our mathematical analysis showed that the consecutive received signals would have very low correlation for the subharmonics. The experimental data from the Levovist® suspension were used to verify the theoretical predictions. It can be shown that the absolute value of the normalized autocorrelation (first lag) of Doppler signals for the subharmonics was much smaller than the fundamental and the second harmonics when the emitted frequency is 2.1 MHz and the acoustic pressure is 0.8 Mpa. In addition, it is found that the correlation value is always below 0.3 when the emitted frequency is swept from 1.5 to 2.5 MHz and the applied pressure is varied from 0.1 to 1.6 Mpa.