Ultrasound-Guided Intravascular Sonothrombolysis With a Dual Mode Ultrasound Catheter: In Vitro Study

Abstract

Thromboembolism in vessels often leads to stroke or heart attack and even sudden death unless brought under control. Sonothrombolysis based on ultrasound contrast agents has shown promising outcome in effective treatment of thromboembolism. Intravascular sonothrombolysis transducer was reported recently for unprecedented sonothrombolysis in vitro. However, it is necessary to provide an imaging guide during thrombolysis in clinical applications for optimal treatment efficiency. In this article, a dual mode ultrasound catheter was developed by combining a 16-MHz high-frequency element (imaging transducer) and a 220-kHz low-frequency element (treatment transducer) for sonothrombolysis in vitro. The treatment transducer was designed with a 20-layer PZT-5A stack with the aperture size of 1.2×1.2 mm², and the imaging transducer with the aperture size of 1.2×1.2 mm² was attached in front of the treatment transducer. Both transducers were assembled into a customized 2-lm 10-Fr catheter. In vitro experiment was carried out using a bovine blood clot. Imaging tests were conducted, showing that the backscattering signals can be obtained with a high signal-to-noise ratio (SNR) for the 16-MHz imaging transducer. Sonothrombolysis was performed successfully that the volume of clot was reduced significantly after the 30-min treatment. The size changes of clot were observed clearly using the 16-MHz M-mode imaging during the thrombolysis. The findings suggest that the proposed ultrasound-guided intravascular sonothrombolysis can be enhanced since the position of treatment transducer can be adjusted with the target at the clot due to the imaging guide.

Fig. 1.

(a) Structure for the stacked transducer; (b) Schematic for the top view of the catheter; (c) Schematic for the side view of transducers and microbubble tube integrated within the catheter; (d) Photos of the fabricated catheter, including treatment and imaging transdcuers.

Fig. 2.

Schematics of the experiment setup for transducer characterizations: (a) Pulse/echo test for the 16 MHz imaging transducer; (b) Pressure output test for the 220 kHz treatment transducer.

Fig. 3.

(a) Experimentals setups for the (a) clot detection in water and (b) the sonothrombolysis with clot detection.

Fig. 4.

(a) Measured impedance of the imaging transducer and (b) Measured pulse-echo response for the imaging transducer.

Fig. 5.

(a) Measured electrical impedance curve of the treatment transducer; (b) Measured pressure output of the treatment transducer at 1 mm; Measured pressure output distributions of the treatment transducer: (c) from the X-Y plane at 1mm from the transducer surface and (d) from the Y-Z plane.

Fig. 6.

Measured clot signals with the imaging transducer in (a) the water tank and (b) the PDMS channel.

Fig. 7.

(a) Photo of sonothrombolysis experiments before and after the treatment and (b) its corresponding M-imaging during 30 min treatment. The detected clot front surface was labelled with the yellow dotted line.