Abstract
In the past decade, ultrasound molecular imaging has become a promising tool for cancer research, but there remain several challenges for its use in vivo. Low adhesion efficiency of microbubbles at the target sites decreases the contrast resolution of ultrasound molecular images. Conventional strategy to image the adherent microbubbles is based the clearance of freely circulating microbubbles after a period of time, which limits the development of real-time ultrasound molecular imaging. Motion artifacts may therefore affect the quality of acquired images. Thus, ultrasound radiation force (USRF) was recently proposed to increase the adhesion efficiency of targeted microbubbles and reduce the imaging time duration. Since ultrasound frequency close to lower resonance frequency of microbubbles can provide available USRF to drive microbubbles, USRF on commercialized microbubbles becomes a potential challenge on high-frequency ultrasound. In this study, we proposed a dual-frequency (DF) excitation with a high-frequency carrier and various low-frequency envelope components to optimize the targeting efficiency of microbubbles. Results show that DF excitation with envelope frequencies (i.e., 10–30 MHz) close to the resonance frequency of submicron in-house bubbles (i.e., 9–35 MHz) resulted in targeting enhancement of 3.3–6.2 folds at the duration of 2 minutes. In addition, the high-frequency carrier of DF excitation provides a more localized microbubbles adhesion area, showing great promise to reduce the biological effect of ultrasound targeted therapy. In the second part, we combined DF excitation with chirp reversal technique (referred to DF-chirp reversal) to selectively image the adherent microbubbles. Since DF chirp excitation can be compressed by matched filtering to suppress tissue components, the contrast-to-tissue ratio can be up to 24.8 dB in-vitro phantom experiments. Therefore, the DF-chirp reversal method has the potential to be implemented in a real-time ultrasound molecular imaging system.