Optimized high frequency nonlinear contrast imaging using self-demodulation

Previously we have shown that a suitable design of the excitation envelope to generate a self-demodulation (SD) signal at the subharmonic (SH) frequency can enhance the SH emission of ultrasound contrast agent (UCA) more than 20 dB at 10 MHz transmit frequency. The SH emission from the UCA is of interest since it is produced only by the UCA and is free of artifacts produced in harmonic imaging modes. In this study we used such optimized excitation combined with conventional nonlinear contrast detection methods such as pulse inversion (PI), amplitude modulation (AM) and a combination on those (AMPI) in an array-based micro-ultrasound system (Vevo 2100) for in vitro and in vivo validation of real time SH imaging at high frequencies. For better axial resolution, short bursts (6-cycle) and for better separation of the SH peak in the frequency domain, long bursts (20-cycle) with rectangular envelope were transmitted with the following pulse sequences: B-mode, PI, AM and AMPI. For the in vitro study, tissue-mimicking material was prepared. Identical rectangular region of interest at the same depth, in the tissue-mimicking material and UCA (MicroMarker), were selected for contrast to tissue ratio (CTR) calculations. For the in vivo validation the chicken embryos were scanned after administering the UCA. In vitro, the best CTR was obtained with PI sequence filtered at the SH frequency with 26 dB enhancement compared with the fundamental B-mode image. Then, performance of SH imaging with PI sequence was validated in vivo in chicken embryo model. This study suggests that SH imaging is feasible with short transmit bursts (6-cycle) and low acoustic pressure (~200 kPa) at high frequencies (>15 MHz) benefiting from the stimulation effect of the S-D signal on the SH emission of UCA.