User:Dm0507/sandbox

Background
Ultrasound enhanced systemic thrombolysis (UEST), also known as sonothrombolysis, is a method that uses ultrasound waves to mechanically break the thrombi, or clots (citation needed). 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 hold the patent for use of trans cranial ultrasound in stroke patients (citation needed). 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 (citation needed). 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 (citation needed)

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 (tPA). Typically, frequencies are in the megahertz (MHz) range (Citation needed), however, some studies suggest that there is no statistically significant difference in frequency use 2MHz or <2MHz in the setting of ischemic stroke (citation needed).

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 (Citation and picture needed from article). However, 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 (Citation needed)

Pulmonary Embolism
Another frequent problem that may require thrombolysis is a pulmonary embolism (PE), which is when a clot forms in a vessel and travels to the lung vasculature. In certain patients with more severe forms of PE (massive or submassive), ultrasound-assisted thrombolysis can improve cardiopulmonary function and reduce the bleeding risk that is accompanied by systemic thrombolysis (citation needed). Ultrasound has been shown to be more effective in reversing the damage to the right heart from strain, and can help return the right heart to the appropriate size, when compared to anticoagulation alone.

Deep Vein Thrombosis
Use of ultrasound enhanced thrombolysis for the treatment of deep vein thromboses (DVTs) 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. (Citation needed)

Cardiac Disease
The use of ultrasound in acute cardiac disease, such as a heart attack, 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. (Citation needed)

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 (Citation needed). 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 during systole and diastole (Citation needed)

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. Additionally, as the technology advances, there could be potential for sonothrombolysis to replace conventional thrombolytics given its safer side-effect profile and good efficacy.