Noninvasive Treatment of Deep Venous Thrombosis Using Pulsed Ultrasound Cavitation Therapy (Histotripsy) in a Porcine Model

Abstract

Purpose-This study evaluated histotripsy as a noninvasive, image-guided method of thrombolysis in a porcine model of deep vein thrombosis. Histotripsy therapy uses short, highintensity, focused ultrasound pulses to cause mechanical breakdown of targeted soft tissue by acoustic cavitation, which is guided by real-time ultrasound imaging. This paper is an in-vivo feasibility study of histotripsy thrombolysis.Methods and Materials-Acute thrombi were formed in the femoral vein of juvenile pigs weighing 30-40 kg by balloon occlusion with two catheters and thrombin infusion. A 10-cm diameter 1-MHz focused transducer was used for therapy. An 8 MHz ultrasound imager was used to align the clot with the therapy focus. Therapy consisted of 5 cycle pulses delivered at a rate of 1 kHz and peak negative pressure between 14-19 MPa. The focus was scanned along the long axis of the vessel to treat the entire visible clot during ultrasound exposure. The targeted region identified by a hyperechoic cavitation bubble cloud was visualized via ultrasound during treatment.Results-Thrombus breakdown was apparent as a decrease in echogenicity within the vessel in 10 of 12 cases, and in 7 cases, improved flow through the vein as measured by color Doppler. Vessel histology showed denudation of vascular endothelium and small pockets of hemorrhage in the vessel adventitia and underlying muscle and fatty tissue, but perforation of the vessel wall was never observed. Conclusions-The results indicate histotripsy has potential for development as a noninvasive treatment for deep vein thrombosis.

Magnetic resonance–guided, high-intensity focused ultrasound sonolysis: potential applications for stroke

“…To address this void, investigators recently made technological advances to render transcranial sonolysis a potential therapeutic option for both AIS-as an alternative for patients with ELVO who are ineligible for EMT or as salvage therapy for patients in whom EMT fails-and ICH-as a neoadjuvant means of clot lysis prior to evacuation. 10,46,51,71 The term "sonothrombolysis" refers to ultrasound-mediated thrombolysis with the concurrent use of adjuvant therapy (for example, tPA, microbubbles); on the other hand, the term "sonolysis" is used when no concurrent adjuvant therapy is employed to achieve clot lysis.…”

“…To address this void, investigators recently made technological advances to render transcranial sonolysis a potential therapeutic option for both AIS-as an alternative for patients with ELVO who are ineligible for EMT or as salvage therapy for patients in whom EMT fails-and ICH-as a neoadjuvant means of clot lysis prior to evacuation. 10,46,51,71 The term "sonothrombolysis" refers to ultrasound-mediated thrombolysis with the concurrent use of adjuvant therapy (for example, tPA, microbubbles); on the other hand, the term "sonolysis" is used when no concurrent adjuvant therapy is employed to achieve clot lysis.63 Although the concept of sonolysis was first proposed by Anschuetz and Bernard in the 1960s, it was not until the introduction of transcranial Doppler ultrasonography (TCD-US) in the 1980s that technological advances permitted the applica-ABBREVIATIONS AIS = acute ischemic stroke; DSA = digital subtraction angiography; ELVO = emergent large-vessel occlusion; EMT = endovascular mechanical thrombectomy; ICH = intracerebral hemorrhage; IV-tPA = intravenous tissue plasminogen activator; MCA = middle cerebral artery; MRg-HIFU = MR-guided, high-intensity focused ultrasound. Stroke is one of the leading causes of death worldwide and a significant source of long-term morbidity.…”

Noninvasive Ureterocele Puncture Using Pulsed Focused Ultrasound: AnIn VitroStudy

“…[8][9][10] With this technology, the US energy is focused and delivered transcutaneously to the target to cause localized tissue breakdown into subcellular fragments. 11 This method has been successfully applied in animal models for treatment of benign prostate hyperplasia, 12 deep vein thrombosis, 13 and tumors. 14 In the present study, we evaluated the feasibility of using histotripsy to generate a mechanical puncture under US image guidance with a tissue model for the ureterocele wall.…”

Enhanced cavitation by using two consecutive ultrasound waves at different frequencies

“…The advantage of these techniques is that they can generate cavitations quickly and noninvasively; however, these techniques may induce unwanted damages. 11 In addition, the onset and efficiency of cavitation is very difficult to control due to tissue heterogeneity. In order to better control cavitation location and easily nucleate cavitation, cavitation nuclei are frequently delivered to the target region.…”