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

Abstract

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 for detecting these changes which 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 100–200 μm resolution. In this article, shaped transmit pulses are applied to imaging the higher broadband harmonic echoes of microbubble contrast agents, and the effects of varying pulse window and phasing on microbubble and tissue harmonic echoes are evaluated using a dual-frequency transducer in vitro and in vivo. An increase in contrast-to-tissue ratio of 6.8 ± 2.3 dB was observed in vitro by using an inverted pulse with a cosine window relative to a non-inverted pulse with a rectangular window. The increase in mean image intensity due to 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 relative to a non-inverted pulse with a rectangular window. Implications for pre-clinical and diagnostic imaging are also discussed.

Contrast Enhanced Superharmonic Imaging for Acoustic Angiography Using Reduced Form-Factor Lateral Mode Transmitters for Intravascular and Intracavity Applications

“…In contrast, superharmonic imaging, where higher order harmonics are detected, provides improved differentiation of UCAs from tissue and higher resolution in the resulting images [21]. Some work have been done to study the optimization of microbubble response, including varying pulse window and phase of the signal, changing the bubble size, adjusting the frame number, and controlling the peak negative pressure [22, 23]. Typically, for non-inertial cavitation superharmonic imaging, higher order non-linear responses are maximized by exciting microbubbles with a large peak negative pressure or at a frequency close to the resonant frequency of the microbubble.…”

Dual-Frequency Piezoelectric Endoscopic Transducer for Imaging Vascular Invasion in Pancreatic Cancer

“…A three-axis computer-controlled motion stage (Newport XPS, Irvine, CA, USA) translates the transducer in the elevation direction to enable 3D imaging [63]. The transducer was excited using a 4 MHz Gaussian-windowed sinusoid [19] (AFG3101) and a 60 dB radiofrequency amplifier (A-500, Electronic Navigation Industries, Rochester, NY, USA). 3D volumes of imaging data were acquired by performing pullback imaging in tissue-mimicking phantoms and in an ex vivo porcine artery.…”

“…Briefly, by transmitting at a lower frequency (< 6 MHz) and receiving at much higher frequencies (≥20 MHz), images can be formed from microbubble-specific signals having amplitudes many times higher than tissue signals [17, 18]. These “superharmonic” or “acoustic angiography” images of microvasculature have contrast-to-tissue ratios of ~25 dB [16, 19, 20] and can be used to quantify vascular characteristics in developing tumors [21–26]. We have also recently demonstrated the ability to use superharmonic signals to perform high resolution functional imaging, including molecular imaging [27, 28] and perfusion imaging [29].…”

Acoustic angiography: a new high frequency contrast ultrasound technique for biomedical imaging

“…Another approach to improving the CTR of acoustic angiography imaging that does not require fabrication of a new dual-frequency transducer or manipulation of microbubble size distributions is the application of a window to the transmitted waveform [65]. In vitro and in vivo experiments were conducted to measure the CTR and contrast enhancement upon implementation of varying shaped low-frequency transmit pulses.…”