Miniaturized Stacked Transducer for Intravascular Sonothrombolysis With Internal-Illumination Photoacoustic Imaging Guidance and Clot Characterization

Abstract

Thromboembolism in blood vessels can lead to stroke or heart attack and even sudden death unless brought under control. Sonothrombolysis enhanced by ultrasound contrast agents has shown promising outcome on effective treatment of thromboembolism. Intravascular sonothrombolysis was also reported recently with a potential for effective and safe treatment of deep thrombosis. Despite the promising treatment results, the treatment efficiency for clinical application may not be optimized due to the lack of imaging guidance and clot characterization during the thrombolysis procedure. In this paper, a miniaturized transducer was designed to have an 8-layer PZT-5A stacked with an aperture size of 1.4 × 1.4 mm² and assembled in a customized two-lumen 10-Fr catheter for intravascular sonothrombolysis. The treatment process was monitored with internal-illumination photoacoustic tomography (II-PAT), a hybrid imaging modality that combines the rich contrast of optical absorption and the deep penetration of ultrasound detection. With intravascular light delivery using a thin optical fiber integrated with the intravascular catheter, II-PAT overcomes the penetration depth limited by strong optical attenuation of tissue. In-vitro PAT-guided sonothrombolysis experiments were carried out with synthetic blood clots embedded in tissue phantom. Clot position, shape, stiffness, and oxygenation level can be estimated by II-PAT at clinically relevant depth of ten centimeters. Our findings have demonstrated the feasibility of the proposed PAT-guided intravascular sonothrombolysis with real-time feedback during the treatment process.

Fig. 1

Schematic of the two-lumen catheter with the stacked transducer. (a) Structure of the stacked transducer. (b) Schematic of the relative position of the transducer, MB tube, and optical fiber. (c) Photograph of the fabricated stacked transducer integrated with the optical fiber.

Fig. 2

Schematic of the in-vitro sonothrombolysis with stacked transducer and internal-illumination photoacoustic imaging guidance. (a) Deep tissue clot detection with photoacoustic tomography. A Polydimethylsiloxane (PDMS) channel containing clot, catheter and optical fiber was immersed in water. A layer of ten-centimeter-thick chicken breast tissue was placed between the PDMS channel and the linear ultrasound transducer that was used for signal detection in photoacoustic imaging. (b) Interior design of the two-lumen catheter for the sonothrombolysis. The miniaturized stacked transducer was mounted in the main lumen with a side lumen for the microbubble (MB) delivery and laser light delivery.

Fig. 3

(a) Simulated and measured impedance curve for the stacked transducer from 0.2 MHz to 1.0 MHz. (b) Measured peak-to-peak (PTP) pressure and peak-negative pressure (PNP) for the stacked transducer with peak-to-peak input driving voltage (Vpp) from 10 V to 100 V (c) Simulated pressure output of the stacked transducer.

Fig. 4

sO2 images of the blood clots beneath ten-centimeter chicken tissue, acquired every 10 minutes with three different treatment conditions: (a) Ultrasound treatment with infusion of microbubbles, (b) Ultrasound treatment only, (c) Microbubble infusion only. The original clot front end is marked by the solid green line and the original clot size is marked by the dashed yellow line. The white arrow indicates the direction of the catheter. The layered structures of the clot may be due to the streaking imaging artifacts as a result of the limited detection aperture of the imaging transducer array. The reverberation of the photoacoustic signals by the tube wall may also contribute to be layered image.

Fig. 5

Acoustic frequency spectra of PA signals acquired at 800 nm before and after the treatment under three conditions: (a) US+MB, (b) US-only, and (c) MB-only. Pre-tmt, pre-treatment; Post-tmt, post-treatment. Fig. 6 Passive cavitation detection under the US+MB and US-only treatment conditions. Averaged frequency amplitude spectra of the test groups for (a) stable cavitation and (b) inertial cavitation (N = 7) (c) Calculated cavitation dose for the inertial cavitation and stable cavitation.

Fig. 6

Clot size reduction and cross-sectional view after 40-min treatment under three treatment conditions: (a) Ultrasound treatment with microbubble infusion (b) Ultrasound treatment only (c) Microbubble infusion only.

Fig. 7

Clot size reduction and cross-sectional view after 40-min treatment under three treatment conditions: (a) Ultrasound treatment with microbubble infusion (b) Ultrasound treatment only (c) Microbubble infusion only.