High-resolution, high-contrast ultrasound imaging using a prototype dual-frequency transducer: in vitro and in vivo studies

Abstract

With recent advances in animal models of disease, there has been great interest in capabilities for highresolution contrast-enhanced ultrasound imaging. Microbubble contrast agents are unique in that they scatter broadband ultrasound energy because of their nonlinear behavior. For optimal response, it is desirable to excite the microbubbles near their resonant frequency. To date, this has been challenging with high-frequency imaging systems because most contrast agents are resonant at frequencies in the order of several megahertz. Our team has developed a unique dual-frequency confocal transducer which enables low-frequency excitation of bubbles near their resonance with one element, and detection of their emitted high-frequency content with the second element. Using this imaging approach, we have attained an average 12.3 dB improvement in contrast-to-tissue ratios over fundamental mode imaging, with spatial resolution near that of the high-frequency element. Because this detection method does not rely on signal decorrelation, it is not susceptible to corruption by tissue motion. This probe demonstrates contrast imaging capability with significant tissue suppression, enabling high-resolution contrast-enhanced images of microvascular blood flow. Additionally, this probe can readily produce radiation force on flowing contrast agents, which may be beneficial for targeted imaging or therapy.

Fig. 1

(a) Schematic for the operation of the prototype dual frequency transducer. The arbitrary waveform generator (AWG) (Sony Tektronix) was triggered to send 512 low-frequency pulses through the RF amplifier (RFA) within each frame of image data by the Vevo770 line trigger. (b) A diagram displaying how the two confocal elements were constructed within the RMV probe scanhead.

Fig. 2

(a) Contrast-to-tissue ratios measured in vitro as a function of frequency at several different mechanical indices of incident pulses. Decibel values are relative to the tissue response at each frequency and MI. (b) Contrast-to-tissue ratios measured in vivo in six different kidneys which were imaged in both high-frequency b-mode (dashed line) and dual-frequency mode (solid line).

Fig. 3

(a) A 2-D transverse slice through a rat kidney with contrast agents seen entering the volume through the large renal vasculature. (b) A 3-D maximum intensity projection through a rendered volume of sequential image slices as seen in (a). The multiple 2-D slices were acquired using a translational motor stage with step sizes of 200 μm. The images analyzed in the CTR portion of this study were identical to the cross-sectional slice seen in (a).

Fig. 4

Example image data collected from the same animal without respiratory gating enabled. (a) B-mode imaging before the introduction of contrast agents. (b) Dual-frequency data while contrast is circulating. (c) Image-subtraction frame while contrast is circulating. Note the strong artifacts near the tissue borders (indicated by white arrows). (d) Power-Doppler with contrast circulating. Small regions of enhanced contrast can be seen near the bottom of the image, although most of ROI is washed out by motion artifact.

Fig. 5

A plot comparing the abilities of the three different imaging modes to monitor contrast flow in the presence of respiratory motion. Values are expressed as a percentage of the seven attempted trials.

Fig. 6

A time-axis projection image produced from bright-field optical video data, which demonstrates the proficiency of the dual-frequency probe at diverting a moving stream of MCAs. The linear flow velocity in this image was 40 mm/s, a comparable speed to a human small artery or large vein.