Contrast-enhanced intravascular ultrasound (CE-IVUS) imaging could provide clinicians a valuable tool to assess cardiovascular risk and guide the choice of therapeutic strategies. In this technical note, we evaluated the feasibility of combining subharmonic and ultraharmonic imaging to improve the performance of CE-IVUS. Vessel phantoms perfused with phospholipid-shelled ultrasound contrast agents were visualized using subharmonic, ultraharmonic, and combined CE-IVUS modes with commercial peripheral and coronary imaging catheters. Flow channels as small as 0.8 mm and 0.5 mm were imaged at 12 MHz and 30 MHz transmit frequencies, respectively. Subharmonic and ultraharmonic imaging modes achieved a contrast-to-tissue ratio (CTR) up to 18.1 ± 1.8 dB and 19.6 ± 1.9 dB at 12 MHz, and 8.8 ± 1.8 and 12.5 ± 1.1 dB at 30 MHz transmit frequencies, respectively. Combining these modes improved the CTR to 32.5 ± 3.0 dB and 25.0 ± 1.6 dB at 12 and 30 MHz transmit frequencies. These results underscore the potential of combined-mode CE-IVUS imaging. Furthermore, the demonstration of this approach with commercial catheters may serve as a first step towards the clinical translation of CE-IVUS.
Imaging using ultrasound contrast agents is highly dependent on the resonant frequency of the population. According to the Marmottant model, modern lipid coated agents have three regimes of resonant frequencies corresponding to the three regimes of bubble dynamics, the buckled, elastic, and ruptured states. The transition from buckled to elastic regime corresponds to the largest change in resonant frequency due to the addition of a second term inversely proportional to the bubbles’ radius. For a 1.75 μm bubble, this corresponds to a change from approximately 1.7 MHz, to approximately 5 MHz, leading to higher image resolution, and better separation between the fundamental and subharmonic components. Here we present a novel ultrathin silicon nitride membrane for this purpose. The membrane itself contains thousands of 1.75 × 50 μm slits and is housed in a centrifuge device. While the exact mechanism is unknown, bubbles that are forced across the membrane during centrifugation show a higher resonant frequency than their strictly size isolated counterparts. In addition, the centrifuged agent also had a lower subharmonic threshold compared to native and size isolated agents, independent of concentration. The possibility of tuning the device to precise frequencies for optimized imaging is also examined.
As part of the development of the MITRE BlueTech Lab, an existing 106 × 40 × 15 ft. underground tank is being repurposed as an underwater acoustic test facility. Here, we report on the development of a procedure to extract anechoic frequency responses from measurements made in the otherwise reverberant environment using exponential sine sweeps. A demonstration of the procedure applied to a small-aperture baffled receiver array is shown, and results are compared to time-gated stepped sine wave measurements. Simple geometric rules to maximize measurement bandwidth while ensuring far-field conditions for both transmitter and receiver array are presented.
Abnormal proliferation of the vasa vasorum has been implicated in the rupture of atherosclerotic plaques. Imaging the vasa vasorum could help clinicians identify rupture-prone plaques and guide the choice of therapy. We hypothesized that subharmonic and ultraharmonic modes can be combined to improve the performance of contrast-enhanced intravascular ultrasound (IVUS) imaging. To test this hypothesis, vessel phantoms perfused with phospholipid-shelled ultrasound contrast agent (Targestar-P®, Targeson, Inc., San Diego, CA) were visualized using either subharmonic, ultraharmonic, or combined subharmonic and ultraharmonic modes. Flow channels, as small as 0.8 mm and 0.5 mm in diameter, were imaged using commercial peripheral and coronary imaging catheters at 12 MHz and 30 MHz transmit frequencies, respectively. Subharmonic and ultraharmonic imaging modes attained contrast-to-tissue ratios (CTRs) of 18 ± 2 dB and 20 ± 2 dB at 12 MHz transmit frequency, and 9 ± 2 dB and 13 ± 1 dB at 30 MHz transmit frequency, respectively. Combining subharmonic and ultraharmonic modes enhanced the CTRs to 33 ± 3 dB and 25 ± 2 dB at 12 MHz and 30 MHz transmit frequencies, respectively. These preliminary findings support the continued investigation of combined subharmonic and ultraharmonic IVUS for vasa vasorum imaging.
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