Optimization of contrast-to-tissue ratio and role of bubble destruction in dual-frequency contrast-specific “acoustic angiography” imaging

Recently, dual-frequency transducers have enabled high-spatial resolution, high-contrast imaging of microvasculature by transmitting at a low frequency and receiving broadband superharmonic echoes from microbubble contrast agents at a higher frequency. In this work, we examine the imaging parameters for optimizing contrast-to-tissue ratio (CTR) for dual-frequency imaging and the relationship between bubble destruction and broadband harmonic signal production. CTR was assessed in vitro by acquiring scattered echoes by bubbles and beef muscle for transmit pressures up to 2 MPa, transmit frequencies from 1.5-8 MHz, and receive frequencies from 7.5 to 25 MHz. Optimum CTR (25.5 dB) was found to occur at the lowest transmit frequencies, though a broad peak exists within the 1.5-3.5 MHz range. At these frequencies, CTR is optimized when receiving at a center frequency of 10 - 15 MHz. A 4 μm-diameter microbubble population yielded ~5 dB higher CTR than a 1 μm population. Single bubble behavior was assessed with simultaneous acoustic and optical recordings. For n=250 single bubbles subjected to five consecutive single-cycle pulses (100-500 kPa), three primary categories of bubble behavior were observed optically: 1) no change in bubble diameter, 2) bubble shrinking (deflation), and 3) immediate bubble destruction (fragmentation). Matched acoustic data indicate that superharmonic signals having the broadest bandwidth and highest energy are associated with shell fragmentation. In the deflation case, a weaker superharmonic signal is produced with an amplitude approximately 25% of the signal in the shell fragmentation case. Similar regimes were observed in vivo, suggesting that bubble diameter, transmit frequency, peak negative pressure, and frame rate must be selected in light of the intended application, accounting for attenuation and local perfusion rate in the region of interest.