Imaging plaque microvasculature with contrast-enhanced intravascular ultrasound (IVUS) could help clinicians evaluate atherosclerosis and guide therapeutic interventions. In this study, we evaluated the performance of chirp-coded ultraharmonic imaging using a modified IVUS system (iLab™, Boston Scientific/Scimed) equipped with clinically available peripheral and coronary imaging catheters. Flow phantoms perfused with a phospholipid-encapsulated contrast agent were visualized using ultraharmonic imaging at 12 MHz and 30 MHz transmit frequencies. Flow channels with diameters as small as 0.8 mm and 0.5 mm were visualized using the peripheral and coronary imaging catheters. Radio-frequency signals were acquired at standard IVUS rotation speed, which resulted in a frame rate of 30 frames/s. Contrast-to-tissue ratios up to 17.9 ± 1.11 dB and 10.7 ± 2.85 dB were attained by chirp-coded ultraharmonic imaging at 12 MHz and 30 MHz transmit frequencies, respectively. These results demonstrate the feasibility of performing ultraharmonic imaging at standard frame rates with clinically available IVUS catheters using chirp-coded excitation.

Characterizing the nonlinear response of microbubble contrast agents is important for their efficacious use in imaging and therapy. In this paper, we report that the subharmonic and ultraharmonic response of lipid-shelled microbubble contrast agents exhibits a strong temporal dependence. We characterized nonlinear emissions from Targestar-P® microbubbles (Targeson Inc., San Diego, CA, USA) periodically for 60 minutes, at 10 MHz excitation frequency. The results revealed a considerable increase in the subharmonic and ultraharmonic response (nearly 12–15 and 5–8 dB) after 5–10 minutes of agent preparation. However, the fundamental and the harmonic response remained almost unchanged in this period. During the next 50 minutes, the subharmonic, fundamental, ultraharmonic, and harmonic responses decreased steadily by 2–5 dB. The temporal changes in the nonlinear behavior of the agent appeared to be primarily mediated by gas-exchange through the microbubble shell; temperature and prior acoustic excitation based mechanisms were ruled out. Further, there was no measurable change in the agent size distribution by static diffusion. We envisage that these findings will help obtain reproducible measurements from agent characterization, nonlinear imaging, and fluid-pressure sensing. These findings also suggest the possibility for improving nonlinear imaging by careful design of ultrasound contrast agents.

The abnormal growth of the vasa vasorum is characteristic of life-threatening atherosclerotic plaques. Intravascular ultraharmonic imaging is an emerging technique that could visualize the vasa vasorum and help clinicians identify life-threatening plaques. Implementing this technique on commercial intravascular ultrasound (IVUS) systems could to accelerate its clinical translation. Our previous work has demonstrated ultraharmonic IVUS imaging with a modified clinical system that was equipped with a commercial 15 MHz peripheral imaging catheter. In the present study, we investigated the feasibility of ultraharmonic imaging with a commercially available 40 MHz coronary imaging catheter. We imaged a flow phantom that had contrast agent microbubbles (Targestar-P-HF, Targeson Inc., CA) perfused in side channels parallel to its main lumen. The transducer was excited at 30 MHz using 10% bandwidth chirp-coded pulses. The ultraharmonic response at 45 MHz was isolated and preferentially visualized using pulse inversion and digital filtering. Side channels with 900 μm and 500 μm diameter were detected with contrast-to-tissue ratios approaching 10 dB for clinically relevant microbubble concentrations. The results of this study indicate that ultraharmonic imaging is feasible with commercially available coronary IVUS catheters, which may facilitate its widespread application in preclinical research and clinical imaging.

An intravascular ultrasound system capable of visualizing microbubble contrast agents could provide functional information for assessing atherosclerotic plaques. The goal of this study was to investigate the feasibility of contrast-enhanced imaging with a modified commercial intravascular ultrasound system. We employed an iLab™ system (Boston Scientific/Scimed, Natick, MA) equipped with an Atlantis™ PV imaging catheter (15-MHz center frequency, 26% fractional bandwidth) to image tissue mimicking phantoms that had contrast agent (Targestar-P®, Targeson Inc., CA) flowing in side channels parallel to the center lumen. Chirp-coded pulses were employed with transmit frequency of 12 MHz and peak pressures ranging from 1–2 MPa. The ultraharmonic response (18 MHz) was isolated from the backscattered radio-frequency using pulse inversion and matched filtering, to produce contrast specific images. We evaluated the detection sensitivity of the agent as a function of microbubble concentration and transmit pulse parameters. The results revealed that side channels with diameters ranging from 500 μm to 2 mm could be visualized for a wide range of concentrations. These results demonstrate that functional imaging of plaque neovascularization is feasible with commercially available intravascular catheters. Further development of such systems can facilitate the widespread use of contrast-enhanced intravascular ultrasound for preclinical research and clinical imaging.

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