Optimization of Contrast-to-Tissue Ratio Through Pulse Windowing in Dual-Frequency "Acoustic Angiography" Imaging

Early-stage tumors in many cancers are characterized by vascular remodeling, indicative of transformations in cell function. We have previously presented a high-resolution ultrasound imaging approach to detecting these changes that is based on microbubble contrast agents. In this technique, images are formed from only the higher harmonics of microbubble contrast agents, producing images of vasculature alone with 100- to 200-μm resolution. In this study, shaped transmit pulses were used to image the higher broadband harmonic echoes of microbubble contrast agents, and the effects of varying pulse window and phasing on microbubble and tissue harmonic echoes were evaluated using a dual-frequency transducer in vitro and in vivo. An increase in the contrast-to-tissue ratio of 6.8 ± 2.3 dB was observed in vitro using an inverted pulse with a cosine window relative to a non-inverted pulse with a rectangular window. The increase in mean image intensity resulting from contrast enhancement in vivo in five rodents was 13.9 ± 3.0 dB greater for an inverted cosine-windowed pulse and 17.8 ± 3.6 dB greater for a non-inverted Gaussian-windowed pulse relative to a non-inverted pulse with a rectangular window. Implications for pre-clinical and diagnostic imaging are discussed.