Safety Evaluation of a Forward-Viewing Intravascular Transducer for Sonothrombolysis: An in Vitro and ex Vivo Study

Goel, Leela; Wu, Huaiyu; Zhang, Bohua; Kim, Jin-Wook; Dayton, Paul A.; Xu, Zhen; Jiang, Xiaoning

doi:10.1016/j.ultrasmedbio.2021.07.018

Cited by 16 publications

(7 citation statements)

References 34 publications

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“…The thrombus debris produced by the power 1.3 W are <20 μm, while 200 μm debris appear in the power of 6.0 W. Even at high power ultrasound, the maximum particle size of thrombus debris produced is below 500 μm. The particle size analysis in our experiment matches well with the study by Goel et al [16] It should be noted that the effect of ultrasound in the sonothrombolysis is to enhance the diffusion of thrombolytic drug to dissolve the thrombus, not to break the thrombus by the mechanical impaction. Therefore, the power of the ultrasound used in IST therapy need to be controlled in the range, within which the thrombolytic efficiency is high, while large debris is not generated.…”

Section: In-vitro Study Of Sonothrombolysissupporting

confidence: 90%

“…It is the first time that we adopt the IST to treat the thrombosis on LVAD. Here, we review clinical studies about thrombolytic technologies on implantable and interventional devices in recent years [ 2 , 3 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] and compare the IST with other currently used thrombolytic technologies, including medical therapy, pump exchange, sonothrombolysis, washout maneuver, and mechanical thrombectomy. Safety and efficiency are focused on in the evaluation.…”

Section: Discussionmentioning

confidence: 99%

“…Medical therapy is usually the first choice to treat the LVAD thrombosis. However, it has the incidence of hemorrhagic stroke, [ 2 , 3 , 15 , 16 , 17 , 18 , 19 , 20 ] and need a relative long treatment time, usually >3 h. [ 2 ] Pump exchange is an urgent treatment, but it has a high surgical risk because most of the patients can't suffer another reopen heart surgery. [ 21 , 22 , 23 , 24 , 25 , 26 ] Washout maneuver is used to remove the thrombus at the inlet of LVAD.…”

Section: Discussionmentioning

confidence: 99%

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Interventional Microbubble Enhanced Sonothrombolysis on Left Ventricular Assist Devices

et al. 2022

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The left ventricular assist device (LVAD) is often used in the treatment of heart failure. However, 4% to 9% implanted LVAD will have thrombosis problem in one year, which is fatal to the patient's life. In this work, an interventional sonothrombolysis (IST) method is developed to realize the thrombolysis on LVAD. A pair of ultrasound transducer rings is installed on the shell of LVAD, and drug-loaded microbubbles are injected into the LVAD through the interventional method. The microbubbles are adhere on the thrombus with the coated thrombus-targeted drugs, and the thrombolytic drugs carried by the bubbles are brought into the thrombus by the cavitation of bubbles under the ultrasound. In a proof-of-concept experiment in a live sheep model, the thrombus on LVAD is dissolved in 30 min, without damages on LVADs and organs. This IST exhibits to be more efficient and safer compared with other thrombolysis methods on LVAD.

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Section: In-vitro Study Of Sonothrombolysissupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Interventional Microbubble Enhanced Sonothrombolysis on Left Ventricular Assist Devices

et al. 2022

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“…Ultrasound can be administered intravascularly (e.g. EKOS Endovascular System, Boston Scientific, Marlborough, MA [ 13 ] and forward facing catheters [ 14 ]) or extracorporeally [ 15 , 16 ]. Bubble activity is the primary catalyst to promote clot degradation [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

et al. 2022

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Deep vein thrombosis is a major source of morbidity and mortality worldwide. For acute proximal deep vein thrombosis, catheter-directed thrombolytic therapy is an accepted method for vessel recanalization. Thrombolytic therapy is not without risk, including the potential for hemorrhagic bleeding that increases with lytic dose. Histotripsy is a focused ultrasound therapy that generates bubble clouds spontaneously in tissue at depth. The mechanical activity of histotripsy increases the efficacy of thrombolytic therapy at doses consistent with current pharmacomechanical treatments for venous thrombosis. The objective of this study was to determine the influence of lytic dose on histotripsy-enhanced fibrinolysis. Human whole blood clots formed in vitro were exposed to histotripsy and a thrombolytic agent (recombinant tissue plasminogen activator, rt-PA) in a venous flow model perfused with plasma. Lytic was administered into the clot via an infusion catheter at concentrations ranging from 0 (control) to 4.54 μg/mL (a common clinical dose for catheter-directed thrombolysis). Following treatment, perfusate samples were assayed for markers of fibrinolysis, hemolysis, and intact red blood cells and platelets. Fibrinolysis was equivalent between the common clinical dose of rt-PA (4.54 μg/mL) and rt-PA at a reduction to one-twentieth of the common clinical dose (0.23 μg/mL) when combined with histotripsy. Minimal changes were observed in hemolysis for treatment arms with or without histotripsy, potentially due to clot damage from insertion of the infusion catheter. Likewise, histotripsy did not increase the concentration of red blood cells or platelets in the perfusate following treatment compared to rt-PA alone. At the highest lytic dose, a refined histotripsy exposure scheme was implemented to cover larger areas of the clot. The updated exposure scheme improved clot mass loss and fibrinolysis relative to administration of lytic alone. Overall, the data collected in this study indicate the rt-PA dose can be reduced by more than a factor of ten and still promote fibrinolysis when combined with histotripsy.

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“…However, in order to keep the ultrasound transducer operating within a safe voltage range, 100 V pp was applied as the maximum input voltage due to the ultrasound transducer material limitation (45% of the AC depoling voltage for PZT-5A ceramics). For the safety of the treatment 57 , 80 V pp was selected as the optimal input voltage for this study.…”

Section: Resultsmentioning

confidence: 99%

A Model of High-Speed Endovascular Sonothrombolysis with Vortex Ultrasound-Induced Shear Stress to Treat Cerebral Venous Sinus Thrombosis

Zhang

Kim

et al. 2022

Preprint

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This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis (CVST). This is a topic of significant importance since current treatment modalities for CVST still fail in as many as 20-40% of the cases and the incidence of CVST has increased since the outbreak of the COVID-19 pandemic. Compared with conventional anticoagulant or thrombolytic drugs, sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves. However, previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes (e.g., recanalization within 30 minutes) in treating large, completely occluded veins or arteries. In this paper, we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wave-matter interaction-induced shear stress to enhance the lytic rate substantially. Our in vitro experiment showed that the lytic rate was increased by at least 64.3 % compared with the nonvortex endovascular ultrasound treatment. A 3.1 g, 7.5 cm long, completely occluded in vitro 3D model of acute CVST was fully recanalized within 8 minutes with a record-high lytic rate of 237.5 mg/min for acute bovine clot in vitro. Furthermore, we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo bovine veins. This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.

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Safety Evaluation of a Forward-Viewing Intravascular Transducer for Sonothrombolysis: An in Vitro and ex Vivo Study

Cited by 16 publications

References 34 publications

Interventional Microbubble Enhanced Sonothrombolysis on Left Ventricular Assist Devices

Interventional Microbubble Enhanced Sonothrombolysis on Left Ventricular Assist Devices

(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

A Model of High-Speed Endovascular Sonothrombolysis with Vortex Ultrasound-Induced Shear Stress to Treat Cerebral Venous Sinus Thrombosis

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