An Integrated System for Superharmonic Contrast-Enhanced Ultrasound Imaging: Design and Intravascular Phantom Imaging Study

Abstract

Objective: Superharmonic contrast-enhanced ultrasound imaging, also called acoustic angiography, has previously been used for the imaging of microvasculature. This approach excites microbubble contrast agents near their resonance frequency and receives echoes at nonoverlapping superharmonic bandwidths. No integrated system currently exists could fully support this application. To fulfill this need, an integrated dual-channel transmit/receive system for superharmonic imaging was designed, built, and characterized experimentally.

Method: The system was uniquely designed for superharmonic imaging and high-resolution B-mode imaging. A complete ultrasound system including a pulse generator, a data acquisition unit, and a signal processing unit were integrated into a single package. The system was controlled by a field-programmable gate array, on which multiple user-defined modes were implemented. A 6-, 35-MHz dual-frequency dual-element intravascular ultrasound transducer was designed and used for imaging.

Result: The system successfully obtained high-resolution B-mode images of coronary artery ex vivo with 45-dB dynamic range. The system was capable of acquiring in vitro superharmonic images of a vasa vasorum mimicking phantom with 30-dB contrast. It could detect a contrast agent filled tissue mimicking tube of 200 μm diameter.

Conclusion: For the first time, high-resolution B-mode images and superharmonic images were obtained in an intravascular phantom, made possible by the dedicated integrated system proposed. The system greatly reduced the cost and complexity of the superharmonic imaging intended for preclinical study. Significant: The system showed promise for high-contrast intravascular microvascular imaging, which may have significant importance in assessment of the vasa vasorum associated with atherosclerotic plaques.

Fig. 1.

(A) Block diagram of the integrated dual-frequency super-harmonic imaging system. Different color shows different power domain: blue: digital supply; green: high voltage for pulser; red, analog supply; purple, low-noise analog DC supply for ADCs. (B) Photograph of the system.

Fig. 2.

(A) FPGA logic block diagrams. Dashed lines show the clock signal. (B) Logic timing of one frame data acquisition. Pulses number 1 and 3 are bipolar pulses for B-mode imaging; Pulses number 2 and 4 are multi-cycle pulse-train for super-harmonics imaging.

Fig. 3.

(A) Photograph of the transducer. The inset shows the front look of the acoustic stack. (B) Acoustic stack of the dual-layer transducer. (C)Experiment setup for vasa vasorum phantom imaging. (D) Microbubble size distribution.

Fig. 4.

Impulse response of the receiver: (A) Input pulse voltage collected by the 2 GHz digital oscilloscope (dashed black) and the received signal (scaled to 1, blue) collected by the system. (B) The spectrum of the input pulse (dashed black), of the received signal (blue) and of analog filter simulation (red).

Fig. 5.

(A) Broad-band pulse and spectrum measured by oscilloscope. (B) 6 MHz pulse train and spectrum measured by oscilloscope. (C) Pulse echo signal of the 35 MHz element collected by the proposed system. (D) Acoustic pressure output of the 6 MHz element measured by the hydrophone, shown in hydrophone voltage.

Fig. 6.

Acoustic pressure collected using a calibrated hydrophone. The transmitting element was excited using a 6 MHz 1-cycle or 2-cycle pulse.

Fig. 7.

Ex vivo B-mode image of the rabbit coronary artery obtained by 35 MHz transducer element.

Fig. 8.

Phantom super-harmonic imaging result. (A) B-mode image, when MCAs were injected into the micro tube. The approximated location of tube is circled with red. (B) Super-harmonic image obtained when MCAs were injected continuously into the micro-tube.

Fig. 9.

Expanded view of super-harmonic image. (A) is redraw from Fig. 8(B). (B) was collected when water was injected into the vessel mimicking tube. (C) and (D) were collected using a different transducer with narrower bandwidth. (D) was collected where the micro-tube ran parallel to the imaging plane. 200 μm along the axial direction is indicated by the red bars.