Ultrasound-enhanced systemic thrombolysis
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Background

Ultrasound enhanced systemic thrombolysis (UEST), also known as sonothrombolysis, is a method that uses ultrasound waves to mechanically break the thrombi, or clots, using the vibration carried via soundwaves. A large portion of initial research was conducted by Christy Holland, a Professor at the University Cincinnati and the Director of the University of Cincinnati Heart, Lung, and Vascular Institute, who also holds the patent for use of trans cranial ultrasound in stroke patients. One of the main studies characterizing the use of UEST in the setting of acute stroke was the CLOTBUST Trial, which was published in 2004 in the Journal of Neuroimaging. Since then, research with UEST has explored its use in other thrombotic scenarios such as pulmonary embolism and deep vein thrombosis. One major advantage of using ultrasound versus systemic thrombolysis is a reduced risk of bleeding, and improved heart function in the case of
pulmonary embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
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Mechanism

UEST works by using ultrasound waves at different frequencies as an additional treatment that works with the conventional thrombolytics such as
tissue plasminogen activator Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. It is a serine protease () found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion ...
(tPA). Typically, frequencies are in the megahertz (MHz) range, however, some studies suggest that there is no statistically significant difference in frequency use 2 MHz or <2 MHz in the setting of ischemic
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
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Various Uses


Ischemic stroke

Transcranial doppler ultrasound was first investigated in 2004, and demonstrated a significant clinical recovery through the use of sonothrombolysis with tPA, specifically through arterial recanalization. Of note, it is important to first rule out hemorrhagic stroke prior to the initiation of thrombolysis. A meta-analysis conducted in 2020 investigating the safety and efficacy of sonothromoblysis in 5 randomized controlled trials demonstrated that there was overall benefit to using sonothrombolysis especially in the setting of a middle cerebral artery occlusion.


Pulmonary Embolism

Another frequent condition that may require thrombolysis is a pulmonary embolism (PE), which is when a clot forms in a vein and travels to the lung vasculature, or forms directly in the lung vasculature. In certain patients with more severe forms of PE (massive or submassive), sonothrombolysis can improve cardiopulmonary function and reduce the bleeding risk that is accompanied by systemic thrombolysis. Ultrasound has been shown to be more effective in reversing the damage to the right heart from strain due to the PE , and can help return the right heart to the appropriate size, when compared to just
anticoagulation Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...
.


Deep Vein Thrombosis

Studies examining the use of ultrasound enhanced thrombolysis for the treatment of deep vein thromboses (DVTs), or a clot located in the veins, are a bit more sparse, with only 1 randomized control trial up to 2018, and with many retrospective studies. A meta-analysis in 2018 looked at the efficacy of ultrasound and found that a large majority achieved significant thrombolysis, which they defined as >50% of the clot. The safety profile was also characterized in this study, and found that it was a relatively safe invasive procedure with only 1 death in 512 procedures and only 3.9% risk of significant bleeding.


Cardiac Disease

The use of ultrasound in acute cardiac disease, such as a
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
, is still in the early stages of investigation. However, recent data does demonstrate that in patients with an ST-segment elevation myocardial infarction, or STEMI, sonothrombolysis may improve flow within the impacted vessels allowing for better cardiac muscle oxygenation. The use of ultrasound was also shown to have improved left heart function several months after the acute event.


Limitations and Future Directions

While there is a lot of promise in the use of sonothrombolysis, there are limitations at this time. For example, in the setting of ischemic stroke, patients with MCA territory stroke benefit the most. Moreover, the thickness of the temporal bone may also reduce efficacy of sonothrombolysis. With regard to use in cardiac disease, the coronary arteries are much more difficult to visualize with ultrasound for several reasons including obstructions and movement of the arteries while the heart contracts and relaxes. As ultrasound technology advances, the applications continue to expand. For instance, the use of a mobile ultrasound that can pair to mobile devices could be used instead of a bulky machine, which could allow for increased access to the technology.{{Cite web, last=Zeldovich, first=Lina, title=Handheld Ultrasound Devices Are Speeding Diagnosis of COVID-19, url=https://www.scientificamerican.com/article/handheld-ultrasound-devices-are-speeding-diagnosis-of-covid-19/, access-date=2022-01-09, website=Scientific American, language=en Additionally, as the technology advances, there could be potential for sonothrombolysis to replace conventional thrombolytics given its safer side-effect profile and good efficacy.


See also

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Reperfusion therapy Reperfusion therapy is a medical treatment to restore blood flow, either through or around, blocked arteries, typically after a heart attack (myocardial infarction (MI)). Reperfusion therapy includes drugs and surgery. The drugs are thrombolytic ...
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Stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
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Thrombolysis Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massive p ...
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Ultrasound Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
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Pulmonary Embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
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Deep Vein Thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...
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Myocardial Infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
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Anticoagulation Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...


References

Medical treatments Ultrasound Medical ultrasonography