Abstract
Purpose
Pulmonary embolism (PE) occurs when a blood clot, usually from the deep veins of the legs, travels through the bloodstream and becomes lodged in one of the arteries of the lungs. This blockage can be life-threatening if it significantly impairs blood flow to the lungs. Current therapies for PE, such as anticoagulation and thrombolytic agents, often require prolonged bed rest and carry risks of complications.
Methods
To overcome these limitations, the study designs a submillimeter miniature ultrasound catheter compatible with human pulmonary arterial vessels. This catheter emits acoustic vortex, generated through unique ultrasound waveform interference, to enhance thrombolysis by inducing streaming and lateral forces in the thrombus area.
Results
The microscopic experiments and in vitro sonothrombolysis experiments indicated that the combination of thrombolytic agents and acoustic vortex can increase the thrombolysis efficiency up to 35% comparing with the t-PA only group. The pig experiments confirmed the performance of the miniature ultrasound catheter, where successful thrombolysis was achieved within 2.5 h, along with reduction of pulmonary artery pressure to normal levels.
Conclusion
Overall, this approach presents a promising solution to improve PE treatment outcomes, potentially reducing treatment durations and complications associated with conventional therapies.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs40846-024-00878-4/MediaObjects/40846_2024_878_Fig1_HTML.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs40846-024-00878-4/MediaObjects/40846_2024_878_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs40846-024-00878-4/MediaObjects/40846_2024_878_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs40846-024-00878-4/MediaObjects/40846_2024_878_Fig4_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs40846-024-00878-4/MediaObjects/40846_2024_878_Fig5_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs40846-024-00878-4/MediaObjects/40846_2024_878_Fig6_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs40846-024-00878-4/MediaObjects/40846_2024_878_Fig7_HTML.png)
Similar content being viewed by others
References
Carson, J. L., Kelley, M. A., Duff, A., Weg, J. G., Fulkerson, W. J., Palevsky, H. I., Schwartz, J. S., Thompson, B. T., Popovich, J., Hobbins, T. E., Spera, M. A., Alavi, A., & Terrin, M. L. (1992). The clinical course of pulmonary embolism. New England Journal of Medicine, 326, 1240–1245. https://doi.org/10.1056/NEJM199205073261902
Goldhaber, S. Z., & Bounameaux, H. (2012). Pulmonary embolism and deep vein thrombosis. The Lancet, 379, 1835–1846. https://doi.org/10.1016/S0140
Wiske, C. P., Shen, C., Amoroso, N., Brosnahan, S. B., Goldenberg, R., Horowitz, J., Jamin, C., Sista, A. K., Smith, D., & Maldonado, T. S. (2020). Evaluating time to treatment and in-hospital outcomes of pulmonary embolism response teams. J vasc surg venous Lymphat Disord (pp. 717–724). Elsevier Inc. https://doi.org/10.1016/j.jvsv.2019.12.077
Goel, L., & Jiang, X. (2020). Advances in sonothrombolysis techniques using piezoelectric transducers. Sensors (Switzerland), 20. https://doi.org/10.3390/s20051288
Robles, K. E., Armbruster, A. L., Austin, S. E., & Baker, J. N. (2022). Utilization of EKOS in patients with pulmonary embolism, innovations: Technology and techniques in cardiothoracic and vascular surgery 17 30–36. https://doi.org/10.1177/15569845211057882
Kolkailah, A. A., Hirji, S., Piazza, G., Ejiofor, J. I., Ramirez, F., Del Val, J., Lee, S., McGurk, S. F., Aranki, P. S., Shekar, T., & Kaneko (2018). Surgical pulmonary embolectomy and catheter-directed thrombolysis for treatment of submassive pulmonary embolism. Journal of Cardiac Surgery, 33, 252–259. https://doi.org/10.1111/jocs.13576
Soltani, A., Volz, K. R., & Hansmann, D. R. (2008). Effect of modulated ultrasound parameters on ultrasound-induced thrombolysis. Physics in Medicine & Biology, 53, 6837–6847. https://doi.org/10.1088/0031-9155/53/23/012
Guo, S., Guo, X., Wang, X., Zhou, D., Du, X., Han, M., Zong, Y., & Wan, M. (2019). Reduced clot debris size in sonothrombolysis assisted with phase-change nanodroplets. Ultrasonics Sonochemistry, 54, 183–191. https://doi.org/10.1016/j.ultsonch.2019.02.001
De Saint Victor, M., Crake, C., Coussios, C. C., & Stride, E. (2014). Properties, characteristics and applications of microbubbles for sonothrombolysis. Expert Opinion on Drug Delivery, 11, 187–209. https://doi.org/10.1517/17425247.2014.868434
Goel, L., Wu, H., Zhang, B., Kim, J., Dayton, P. A., Xu, Z., & Jiang, X. (2021). Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots. Microsyst Nanoeng, 7. https://doi.org/10.1038/s41378-020-00228-9
Liu, Y., & Luo, J. (2023). Experimental study on damage mechanism of blood vessel by cavitation bubbles. Ultrasonics Sonochemistry, 99. https://doi.org/10.1016/j.ultsonch.2023.106562
Kang, S. T., & Yeh, C. K. (2010). Potential-well model in acoustic tweezers. Ieee Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 57, 1451–1459. https://doi.org/10.1109/TUFFC.2010.1564
Lo, W. C., Fan, C. H., Ho, Y. J., Lin, C. W., & Yeh, C. K. Tornado-inspired acoustic vortex tweezer for trap** and manipulating microbubbles, (n.d.). https://doi.org/10.1073/pnas.2023188118/-/DCSupplemental
Kim, H., Zhang, B., Wu, H., Yao, J., Shi, C., & Jiang, X. (2023). Vortex-ultrasound for microbubble-mediated thrombolysis of retracted clots. Applied Physics Letters, 123. https://doi.org/10.1063/5.0155223
Khan, K., Yamamura, D., Vargas, C., Alexander, T., & SuraniS.R. (2019). The role of EkoSonic endovascular system or EKOS® in pulmonary embolism. Cureus. https://doi.org/10.7759/cureus.6380
Zhou, Y., Murugappan, S. K., & Sharma, V. K. (2014). Effect of clot aging and cholesterol content on ultrasound-assisted thrombolysis. Transl Stroke Res, 5, 627–634. https://doi.org/10.1007/s12975-014-0332-3
Acconcia, C., Leung, B. Y. C., Manjunath, A., & Goertz, D. E. (2014). Interactions between individual ultrasound-stimulated microbubbles and fibrin clots. Ultrasound in Medicine and Biology, 40, 2134–2150. https://doi.org/10.1016/j.ultrasmedbio.2014.03.008
Schultz, J., Andersen, A., Gade, I. L., Ringgaard, S., Kjaergaard, B., & Nielsen-Kudsk, J. E. (2018). A porcine in-vivo model of acute pulmonary embolism. Pulm Circ, 8. https://doi.org/10.1177/2045893217738217
Shackelford, C., Long, G., Wolf, J., Okerberg, C., & Herbert, R. (2002). Quantitative toxicologic pathology qualitative and quantitative analysis of nonneoplastic lesions in toxicology studies.
Acknowledgements
The authors gratefully acknowledge Dr. Wei-Chen Lo and I-Ta Chung for manufacturing the submillimeter ultrasound transducer and the support of the National Science and Technology Council, Taiwan 110-2221-E-007-019-MY3, 110-2622-B-007-002, 111-2622-B-007-001 and 111-2221-E-007-019-MY3.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethics Approval
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the IACUC of Pigmodel Animal TechnoIogy Co., Ltd. (Date: 2023/11/19;No R1_PIG-111012 and Date: 2023/12/27; PIG-112013).
Conflict of Interest
The authors have no relevant financial or non-financial interests to disclose.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Hsieh, ZH., Lai, CY., Chen, NH. et al. Acoustic Vortex-Assisted Thrombolysis Treatment in a Pulmonary Embolism Model Using a Miniature Ultrasound Catheter. J. Med. Biol. Eng. 44, 478–487 (2024). https://doi.org/10.1007/s40846-024-00878-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40846-024-00878-4