The evidence on ultrasound thrombolysis read here stops at clots in vitro and at pigs: of the four studies, two were done in pigs and two on clots in vitro, and there are no clinical case results yet. In pigs, a vortex catheter under one millimeter wide (its tip uses interference of sound waves to create a swirling flow) cleared the clot in a pulmonary embolism model within two and a half hours, and pulmonary artery pressure returned to normal (Hsieh et al., 2024); microtripsy delivered from outside the body restored or markedly increased blood flow in 13 of 14 pigs in a deep vein thrombosis model (Zhang et al., 2017). On clots in vitro, vortex ultrasound reached a peak lysis rate of about 30% in retracted clots (clots that have tightened) versus about 80% in unretracted ones (Kim et al., 2023); in highly retracted clots, histotripsy plus a clot-dissolving drug recovered about 85% of flow, and histotripsy plus saline about 60% (Yang et al., 2024). Bleeding risk in people, whether clot fragments travel downstream, and which clot age suits which approach remain unanswered by all four studies.
Hearing "ultrasound thrombolysis," many people picture sound shattering a clot with no drug needed. That is only partly right. For the catheter-based approaches placed inside the vessel, neither of the two studies read here relies on ultrasound alone: the vortex stirs and applies force to help a clot-dissolving drug or microbubbles work (Hsieh et al., 2024; Kim et al., 2023). The approach that fires from outside the body and leans less on drugs is a separate route, and so far it has been tested only in pigs and on clots in vitro.
Why clots form inside blood vessels
Blood inside a vessel is a flowing liquid, and it clots more easily under three conditions: slow flow, an injured vessel wall, and blood that clots readily. Sitting still for long periods or lying in bed after surgery slows blood in the leg veins; injury to the inner wall triggers clotting; some diseases or constitutions make blood clot more easily. The three often occur together.
A clot that forms on the vessel wall and stays put is a thrombus; one that breaks loose, travels with the blood and lodges in another vessel is an embolus, and the blockage it causes is an embolism. The two locations discussed most often are the deep veins of the leg (deep vein thrombosis) and the arteries of the lung (pulmonary embolism); the clots in pulmonary embolism usually come from the deep veins of the leg (Hsieh et al., 2024).
A clot also changes after it forms: it gradually contracts and becomes dense, which the research calls "retraction." A retracted clot is harder to treat than a fresh one; in many deep vein thrombosis cases, the chronic thrombi often respond poorly to standard catheter-directed therapy (Yang et al., 2024).
How clots are treated now, and at what cost
Treatment falls broadly into three kinds:
- Anticoagulants, which stop the clot from growing and let the body dissolve it slowly
- Thrombolytic drugs, which dissolve the clot directly
- Catheter procedures, which bring a catheter next to the clot to deliver drug on the spot, aspirate it or break it up
The standard treatment for deep vein thrombosis is catheter-directed anticoagulants or thrombolytics (Yang et al., 2024).
The cost sits with the drugs. Thrombolytics travel with the blood through the whole body and do not act on the clot alone, so bleeding risk rises with them. Anticoagulant and thrombolytic treatment of pulmonary embolism often requires prolonged bed rest and carries a risk of complications (Hsieh et al., 2024). This section is clinical background, not a result from the four studies.
So ultrasound became another route
The motivation is straightforward: ultrasound can apply force directly to the thrombus, with fewer side effects expected (Kim et al., 2023). A catheter inside a vessel is thin, its transducer aperture is small, and the efficiency with which sound radiates outward is limited (Kim et al., 2023); the vortex idea uses interference of sound waves to create shear stress and flow around the thrombus and so help lysis along (Hsieh et al., 2024; Kim et al., 2023).
Besides lysis inside the catheter, there is another route: sending sound in from outside the body. Histotripsy fires ultrasound from outside to create controlled cavitation at the target and fractionate tissue into acellular debris; microtripsy is one way of carrying out this technique, designed to improve targeting accuracy and avoid damaging surrounding tissue (Zhang et al., 2017).
| Vortex inside the catheter | Extracorporeal histotripsy (including microtripsy) | |
|---|---|---|
| Where the ultrasound comes from | A catheter goes into the vessel, next to the clot | Fired from outside the body (the controls in Yang et al., 2024 also include catheter-delivered drug) |
| Drug or microbubbles alongside | Neither of the two studies here uses ultrasound alone: Hsieh combines it with a thrombolytic drug, and the title of Kim's study specifies microbubble mediation | Zhang's abstract mentions no accompanying drug; Yang's "histotripsy plus saline" group received no drug and still showed a clear effect |
| Advantage | Energy close to the clot, with a localized area of action | Energy concentrated at the focus, with accurate targeting (Zhang et al., 2017) |
| Limits seen in these four studies | Much weaker effect on retracted clots (Kim et al., 2023) | Where fragments go after breakup is mentioned only by Zhang, who wrote only "no sign of pulmonary embolism" |
There are three limits, all read from these four studies. First, retracted clots are hard to clear: Kim's vortex ultrasound reached a peak lysis rate in retracted clots of only about 40% of that in unretracted clots (Kim et al., 2023). Second, once a clot is broken up, fragments may travel downstream with the blood; of the four abstracts, only Zhang's mentions this. Third, the results of all four come from clots in vitro or pigs, not patients.
What each of the four studies did
| Study | Model and approach | Results in the abstract | What the abstract does not say |
|---|---|---|---|
| Hsieh et al. (2024) | Pig pulmonary embolism model; a vortex catheter under one millimeter wide; combined with the thrombolytic drug t-PA in the in vitro experiments | In vitro: combined use raised thrombolysis efficiency by up to about 35% over t-PA alone. Pig: successful thrombolysis within two and a half hours, with pulmonary artery pressure back to normal | Number of pigs, whether the pig experiment used a drug, bleeding, where fragments go |
| Kim et al. (2023) | Clots in vitro; an endovascular vortex transducer, with microbubble mediation named in the title | Peak lysis rate: about 80% for unretracted clots and about 30% for retracted clots; about 50% higher than non-vortex ultrasound, for both retracted and unretracted | Sample size, comparison with a thrombolytic drug, where fragments go |
| Zhang et al. (2017) | Pig deep vein thrombosis (about 35 kg, 14 pigs); microtripsy fired from outside the body | Flow restored or markedly increased in 13 of 14; the reopened channel reached over 60% of vessel diameter at most; about 16 minutes per centimeter of thrombus; only mild hemolysis; after two weeks of recovery no vessel-wall damage, venous valves preserved, no sign of pulmonary embolism | Results in people, the effect of clot age |
| Yang et al. (2024) | In vitro, highly retracted porcine clots in a flow model of occlusive deep vein thrombosis, treated for one hour | Controls recovered under 10% of flow; histotripsy plus thrombolytic drug about 85%, plus saline about 60%; the microbubble contrast agent DEFINITY added nothing | Sample size of each group, where fragments go |
Figures in this table are rounded for readability; exact values and measurement conditions are in the references.
Three things in this table are easy to misread.
First, the four sets of numbers cannot be lined up to see which is larger. Kim measured "lysis rate," Yang measured "flow recovery," and Hsieh and Zhang looked at flow and pressure in pigs; with different endpoints and different clots, "about 80%" and "about 85%" were not measured with the same ruler.
Second, Zhang's "no vessel-wall damage after two weeks" rests on the two-week group of 4 pigs; the other 10 were euthanized the same day (Zhang et al., 2017). The phrase "no sign of pulmonary embolism" belongs only to Zhang's deep vein model and cannot be carried over to the other three.
Third, Yang's result offers one more piece of information in reverse: in highly retracted clots, the catheter-drug control recovered under 10% of flow, histotripsy with saline reached about 60%, and adding the drug brought it to about 85% (Yang et al., 2024). That suggests the extracorporeal approach depends less on the drug, but it remains a result on clots in vitro.
What none of the four studies answers
Taken together, the four make two things fairly clear, that the energy is comparatively local and that retracted clots are still within reach, yet three questions have no answer.
- Bleeding in people. The four studies used pigs and clots in vitro; none measured bleeding risk in patients. Whether leaning less on drugs means lower bleeding risk has no data in people.
- Fragments going downstream. Where fragments go after a clot is broken up is mentioned only by Zhang, who wrote "no sign of pulmonary embolism" (Zhang et al., 2017), and that applies only to their deep vein model; the abstracts of the other three do not report fragments.
- Which clot age suits which approach. Zhang used acute thrombi, Yang used highly retracted clots, Kim compared retracted with unretracted, and Hsieh's abstract does not say; no study matched clots of different ages to different approaches, so a conclusion such as "fresh clots suit the catheter, old clots suit the extracorporeal approach" has no basis yet.
Frequently Asked Questions
What is the difference between a thrombus and an embolus?
A clot that forms on the vessel wall and stays put is a thrombus; one that breaks loose and lodges in another vessel with the blood flow is an embolus. The clots in pulmonary embolism usually come from the deep veins of the leg (Hsieh et al., 2024).
What is ultrasound thrombolysis?
It uses ultrasound energy to help dissolve a clot. There are two kinds: a catheter carrying an ultrasound transducer goes into the vessel and applies force next to the clot; or ultrasound is fired from outside the body to create controlled cavitation at the clot and break it up (Kim et al., 2023; Zhang et al., 2017).
Does ultrasound thrombolysis always need a clot-dissolving drug?
Not always; it depends on the approach. Neither of the two vortex studies read here uses ultrasound alone: Hsieh combined the vortex with a thrombolytic drug, and in vitro thrombolysis efficiency rose by up to about 35% over t-PA alone (Hsieh et al., 2024); the title of Kim's study specifies microbubble mediation (Kim et al., 2023). Among the extracorporeal histotripsy studies, Yang's "plus saline" group received no drug and recovered about 60% of flow, while adding the thrombolytic drug gave about 85% (Yang et al., 2024).
Have these results been verified in patients?
No. In the four studies read here, the results come from pigs or clots in vitro, not patients. This article does not assess other ultrasound-assisted catheter systems already in clinical use; that is a separate body of evidence.
Can fragments travel elsewhere after a clot is broken up?
This is a practical concern in the field, and of the four abstracts only Zhang's mentions it: in their deep vein thrombosis model they wrote "no sign of pulmonary embolism" (Zhang et al., 2017). That statement belongs only to that study's pig model; the other three do not report where fragments go, and it cannot vouch for them.
Why are retracted clots especially hard to treat?
A clot gradually contracts and becomes dense; in many deep vein thrombosis cases, the chronic thrombi often respond poorly to standard catheter-directed therapy (Yang et al., 2024). In Kim's in vitro experiments, vortex ultrasound reached a peak lysis rate of about 30% in retracted clots and about 80% in unretracted ones (Kim et al., 2023).
Why use pigs for thrombosis research?
The pig cardiovascular system is the closest to the human one in anatomy, physiology, metabolism and immune response, which is why the pig is the main animal model for preclinical testing of cardiovascular devices (Jia et al., 2024). Why pigs suit cardiovascular research is covered in A Pig's Heart, a Human's Catheter: The Science of Cardiovascular Device Testing.
References
Hsieh, Z.-H., Lai, C.-Y., Chen, N.-H., & Yeh, C.-K. (2024). Acoustic vortex-assisted thrombolysis treatment in a pulmonary embolism model using a miniature ultrasound catheter. Journal of Medical and Biological Engineering, 44(3), 478–487. https://doi.org/10.1007/s40846-024-00878-4
Jia, H., Chang, Y., & Song, J. (2024). The pig as an optimal animal model for cardiovascular research. Lab Animal, 53, 136–147. https://doi.org/10.1038/s41684-024-01377-4
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(7), Article 073701. https://doi.org/10.1063/5.0155223
Yang, S., Zemzemi, C., Escudero, D. S., Vela, D. C., Haworth, K. J., & Holland, C. K. (2024). Histotripsy and catheter-directed lytic: Efficacy in highly retracted porcine clots in vitro. Ultrasound in Medicine & Biology, 50(8), 1167–1177. https://doi.org/10.1016/j.ultrasmedbio.2024.04.002
Zhang, X., Macoskey, J. J., Ives, K., Owens, G. E., Gurm, H. S., Shi, J., Pizzuto, M., Cain, C. A., & Xu, Z. (2017). Non-invasive thrombolysis using microtripsy in a porcine deep vein thrombosis model. Ultrasound in Medicine & Biology, 43(7), 1378–1390. https://doi.org/10.1016/j.ultrasmedbio.2017.01.028