This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis (CVST). This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20% to 40% of the cases, and the incidence of CVST has increased since the outbreak of the coronavirus disease 2019 pandemic. Compared with conventional anticoagulant or thrombolytic drugs, sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves. However, previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes (e.g., recanalization within 30 min) in treating large, completely occluded veins or arteries. Here, we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wave-matter interaction-induced shear stress to enhance the lytic rate substantially. Our in vitro experiment showed that the lytic rate was increased by at least 64.3% compared with the nonvortex endovascular ultrasound treatment. A 3.1-g, 7.5-cm-long, completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot in vitro. Furthermore, we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins. This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.
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Vortex-ultrasound for microbubble-mediated thrombolysis of retracted clots
Endovascular sonothrombolysis has gained significant attention due to its benefits, including direct targeting of the thrombus with sonication and reduced side effects. However, the small aperture of endovascular transducers restricts the improvement of their potential clinical efficiency due to inefficient acoustic radiation. Hence, in an earlier study, we used vortex ultrasound with an endovascular ultrasound transducer to induce shear stress and enhance the clot lysis. In this study, the vortex acoustic transduction mechanism was investigated using numerical simulations and hydrophone tests. Following this characterization, we demonstrated the performance of the vortex ultrasound transducer in thrombolysis of retracted clots in in vitro tests. The test results indicated that the maximum lysis rates were 79.0% and 32.2% with the vortex ultrasound for unretracted and retracted clots, respectively. The vortex ultrasound enhanced the efficiency of the thrombolysis by approximately 49%, both for retracted and unretracted clots, compared with the typical non-vortex ultrasound technique. Therefore, the use of endovascular vortex ultrasound holds promise as a potential clinical option for the thrombolysis of retracted clots.
more » « less- Award ID(s):
- 2424077
- PAR ID:
- 10507921
- Publisher / Repository:
- Applied Physics Letters
- Date Published:
- Journal Name:
- Applied Physics Letters
- Volume:
- 123
- Issue:
- 7
- ISSN:
- 0003-6951
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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In modal testing, a common excitation method is a transducer in mechanical contact with the object under test. However, for some structures it is desirable to excite vibrations without physical contact. One promising excitation technique is the acoustic radiation force. However, a challenge in using this technique is that the acoustic radiation force is spread out over a finite-diameter focal region. We describe a method to directly measure the spatial distribution of this force. An ultrasound transducer emitted sine waves with frequencies of, for example f1 = 600.610 kHz and f2 = 600 kHz; the resulting radiation force had a component at the difference frequency f1-f2 = 610 Hz. A MicroAcoustic Instruments BAT6 ultrasound transducer was focused to an approximately 2 mm diameter spot on a 19.6 by 8.1 by 0.37 mm clamped-free brass cantilever with a 610 Hz fundamental frequency. A vibrometer measured the response as this focus spot traversed the edge of the cantilever. This enabled determination of the distribution of the acoustic radiation force being delivered by the transducer. This may be helpful in future studies that involve modeling the force applied to a structure using the acoustic radiation force.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1063/5.0155223
