Dual high-frequency difference excitation for contrast detection

Stimulating high-frequency nonlinear oscillations of ultrasound contrast agents is helpful to distinguish microbubbles from background tissues. Nevertheless, inefficiency of such oscillations from most commercially available contrast agents and intense attenuation of the resultant high-frequency harmonics limit microbubble detection with high-frequency ultrasound. To avoid this high-frequency nature, we devised and explored a dual-frequency difference excitation technique to induce efficiently low-frequency, rather than high-frequency, nonlinear scattering from microbubbles by using high-frequency ultrasound. The proposed excitation pulse is comprised of 2 high-frequency sinusoids with frequency difference subject to the microbubble resonance frequency. Its envelope, with frequency being the difference between the 2 frequencies, is used to stimulate nonlinear oscillation of microbubbles for the consonant low-frequency harmonic generation, whereas high-imaging resolution is retained because of narrow high-frequency transmit beams. Hydrophone measurements and phantom experiments of speckle-generating flow phantoms were performed to demonstrate the efficacy of the proposed technique. The results show that, especially when the envelope frequency is near the microbubbleiquests resonance frequency, the envelope of the proposed excitation pulse can induce significant nonlinear scattering from microbubbles, the induced nonlinear responses tend to increase with the pulse pressures, and up to 26 dB and 36 dB contrast-to-tissue ratios with second- and fourth-order nonlinear responses, respectively, can be obtained. Potential applications of this method include microbubble fragmentation and cavitation with high-frequency ultrasound.