Abstract
Ultrasound radiation force (USRF) is commonly used to facilitate the efficiency of targeted bubble adhesion. Previous reports showed that USRF provides better performance as USRF frequency close to bubbles’ resonant frequency (e.g., several megahertz). However, USRF in low-frequency ultrasound suffers from a large sample volume such that USRF cannot be pinpointed to a specified region of interest. In this study, we proposed a high-frequency dual-frequency (DF) excitation with a low frequency envelope component as USRF while retaining a high spatial resolution. DF pulse is an amplitude modulated wave comprising two sinusoids (Fig. (a)). We fabricated lipid-based bubbles with mean sizes of 2 μm and their resonant frequency was close to 3-MHz. To investigate the targeting efficiencies, two DF pulses with envelope frequencies of 3 MHz (DF-3) and 10 MHz (DF-10) at 25-MHz carrier frequency, and a 25-MHz toneburst waveform with acoustic pressure of 50 kPa and PRF of 2 kHz were adopted. The experimental setup was illustrated in Fig. (b). We used a flow phantom for mimicking receptor-ligand mediated bubbles adhesion and monitored targeted bubbles adhesion simultaneously by a 40-MHz ultrasound imaging system. Figures (c) show the time course images of bubbles adhesion with the quantitative results. The efficiency of bubbles adhesion was calculated the intensity changes in ROI. The DF-3 and DF-10 waveforms performed 2.44 and 1.56 folds enhancement with respect to the cases without USRF, respectively. However, 25-MHz toneburst only had 1.1 folds. The results indicate that high-frequency DF excitation indeed produces a strong USRF and enhances the efficiency of bubbles adherent as its envelope frequency close to bubbles’ resonant frequency. In addition, high-frequency DF excitation provides a narrower sample volume and hence it can generate more localized bubbles adherent by USRF