Abstract
Small animal models have been widely used in drug development and testing. The high-frequency (> 10 MHz) contrast-enhanced ultrasound imaging system provides higher spatial resolution and imaging sensitivity. Nevertheless, nonlinear contrast detection generally suffers from the lower sensitivity at high frequency ultrasound due to the fact that most commercial contrast agents are originally designed to resonate at lower frequencies ranging from 2-3 MHz. To overcome the problem as mentioned above, we proposed an amplitude-modulation chirp imaging (AMCI) method for bubbles detection at high frequency ultrasound. The low-frequency tone burst (pumping wave) was used to manipulate the acoustic cross section of the ultrasound contrast agents (UCAs), and the high-frequency chirp (imaging wave) was used for high-resolution contrast imaging. Here, a pumping wave of 9 MHz is combined with a imaging wave of 31.5 MHz. The changes of acoustic cross section of the UCAs result in periodic changes in the amplitude of the backscattered chirp signal, forming amplitude-modulated chirp terms of 22.5 MHz. The chirp component is then extracted by a band-pass filter (BPF). Then a compression filter is used to recover axial resolution, and even further improve the signal-to-noise ratio (SNR) and contrast-to-tissue ratio (CTR). In vitro measurements were performed to evaluate the CTR values by using AMCI, traditional second- and ultra-harmonic imaging techniques. The self-made microbubbles used in these measurements were composed of C3F8 gas core encapsulated by a lipid shell. The microbubbles concentration was 4.1 × 1011/ml and the size distribution was ranging from 0.1 to 2.4 μm. The peak resonance frequency occurs around 7.5 MHz. Embedded in the phantom was a wall-less vessel of 0.5-mm diameter in which the self-made microbubbles in 1:10000 dilution were flowing. The results indicate that AMCI can provide 3 to 14 dB more agent-to-tissue contrast than those in traditional second- and ultra-harmonic imaging techniques and with a similar axial resolution. The CTR rises from 7 dB to 13 dB after using pulse compression technique. The results show that AMCI technique also performed a better ability of tissue suppression in the phantom experiments. Potential applications include increasing operating frequency of imaging wave to 30-50 MHz to achieve a higher spatial imaging resolution and applying the AMCI in ultrasound molecular imaging.