Sonothrombolysis

Bader, Kenneth B.; Bouchoux, Guillaume; Holland, Christy K.

doi:10.1007/978-3-319-22536-4_19

Cited by 63 publications

(57 citation statements)

References 220 publications

(352 reference statements)

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“…Sonothrombolysis employs low intensity ultrasound to improve the efficacy of thrombolytic agents such as rt-PA or injected microbubbles for contrast enhancement (Porter et al 1996; Behrens et al 1999; Datta et al 2008; Holland et al 2008; Brown et al 2011; Hitchcock et al 2011). Various sonothrombolysis therapies have shown recent successes in the treatment of DVT and stroke in both animal and clinical trials in recent years (Raabe 2006; Bader et al 2016). However, pharmaceutical thrombolysis has been shown to be ineffective in the treatment of retracted clots (Blinc et al 1992; Kunitada et al 1992; Sutton et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive Thrombolysis Using Microtripsy in a Porcine Deep Vein Thrombosis Model

Zhang

Macoskey

Ives

et al. 2017

Ultrasound in Medicine & Biology

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Histotripsy is a noninvasive therapeutic technique that uses ultrasound generated from outside the body to create controlled cavitation in targeted tissue, and fractionates it into acellular debris. We have developed a new histotripsy approach, termed microtripsy, to improve targeting accuracy and to avoid collateral tissue damage. This in vivo study evaluates the safety and efficacy of microtripsy for noninvasive thrombolysis in a porcine deep vein thrombosis (DVT) model. Acute thrombi were formed in left femoral veins of pigs (~35 kg) by occluding the vessel using two balloon catheters and infusing with thrombin. Guided by real-time ultrasound imaging, microtripsy thrombolysis treatment was conducted in 14 pigs. 10 pigs were euthanized on the same day (acute) and 4 at 2 weeks (subacute). To evaluate vessel damage, 30-min free-flow treatment in right femoral vein (no thrombus) was also conducted in 8 acute pigs. Blood flow was successfully restored or significantly increased after treatment in 13 out of the 14 pigs. The flow channels reopened by microtripsy had a diameter up to 64% of the vessel diameter (~6 mm). The average treatment time was 16 minute per cm-long thrombus. Only mild intravascular hemolysis was induced during microtripsy thrombolysis. No damage was observed on vessel walls after two weeks of recovery, venous valves were preserved, and there was no sign of pulmonary embolism. The results of this study indicate that microtripsy has the potential to be a safe and effective treatment for DVT in a porcine model.

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Section: Discussionmentioning

confidence: 99%

Non-Invasive Thrombolysis Using Microtripsy in a Porcine Deep Vein Thrombosis Model

Zhang

Macoskey

Ives

et al. 2017

Ultrasound in Medicine & Biology

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“…23,35,67 Inertial acoustic cavitation is the primary mechanism by which MRg-HIFU thrombolysis achieves clot disintegration. 6,11,33,45,57,71,73 Acoustic waves impart momentum to the fluid immediately surrounding the clot, creating microbubbles. 45,73 These microbubbles rapidly collapse along the clot surface, emitting shock waves and liquid jet speeds of more than 1 km/sec, which promote thrombolysis.…”

Section: Technology and Techniquesmentioning

confidence: 99%

“…However, low-frequency waves can be difficult to focus, resulting in thermal and mechanical damage to adjacent tissues. 6,23,58,68,72 Several techniques have been developed to improve the safety and efficiency of MRg-HIFU thrombolysis. The presence of intracranial standing waves secondary to resonance from acoustic reflections within the cranial vault can have unpredictable and detrimental effects, including the formation of unexpected hot spots and an elevated risk of ICH.…”

Section: Technology and Techniquesmentioning

confidence: 99%

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

Ilyas

Chen

Ding

et al. 2018

Neurosurgical Focus

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Stroke is one of the leading causes of death worldwide and a significant source of long-term morbidity. Unfortunately, a substantial number of stroke patients either are ineligible or do not significantly benefit from contemporary medical and interventional therapies. To address this void, investigators recently made technological advances to render transcranial MR-guided, high-intensity focused ultrasound (MRg-HIFU) sonolysis a potential therapeutic option for both acute ischemic stroke (AIS)—as an alternative for patients with emergent large-vessel occlusion (ELVO) who are ineligible for endovascular mechanical thrombectomy (EMT) or as salvage therapy for patients in whom EMT fails—and intracerebral hemorrhage (ICH)—as a neoadjuvant means of clot lysis prior to surgical evacuation. Herein, the authors review the technological principles behind MRg-HIFU sonolysis, its results in in vitro and in vivo stroke models, and its potential clinical applications. As a noninvasive transcranial technique that affords rapid clot lysis, MRg-HIFU thrombolysis may develop into a therapeutic option for patients with AIS or ICH. However, additional studies of transcranial MRg-HIFU are necessary to ascertain the merit of this treatment approach for thrombolysis in both AIS and ICH, as well as its technical limitations and risks.

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“…Residual thrombus is associated with increased rates of post thrombotic syndrome (Avgerinos et al 2015), and reoccurrence of thrombus formation in DVT (Watson et al 2009). Histotripsy as a stand-alone therapy neglects the known synergy between ultrasound and thrombolytic drugs (Bader et al 2015a). The addition of a thrombolytic would further break down thrombus debris generated during the histotripsy ablation, minimizing the potential for pulmonary embolism or thrombogenic particulates.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of histotripsy combined with rt-PAin vitro

et al. 2016

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Histotripsy, a form of therapeutic ultrasound that uses the mechanical action of microbubble clouds for ablation lysis, is under development to treat chronic deep vein thrombosis (DVT). We hypothesize that combining thrombolytic agents with histotripsy will enhance clot lysis. Recombinant tissue plasminogen activator (rt-PA) and rt-PA-loaded echogenic liposomes that entrain octafluoropropane microbubbles (OFP t-ELIP) were used in combination with highly shocked histotripsy pulses. Fully retracted porcine venous clots, with similar features of DVT occlusions, were exposed either to histotripsy pulses alone (peak negative pressures of 7–20 MPa), histotripsy and OFP t-ELIP, or histotripsy and rt-PA. Microbubble cloud activity was monitored with passive cavitation imaging during histotripsy exposure. The power levels of cavitation emissions from within the clot were not statistically different between treatment types, likely due to the near instantaneous rupture and deletion of OFP t-ELIP. The thrombolytic efficacy was significantly improved in the presence of rt-PA. These results suggest the combination of histotripsy and rt-PA could serve as a potent therapeutic strategy for the treatment of DVT.

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Sonothrombolysis

Cited by 63 publications

References 220 publications

Non-Invasive Thrombolysis Using Microtripsy in a Porcine Deep Vein Thrombosis Model

Non-Invasive Thrombolysis Using Microtripsy in a Porcine Deep Vein Thrombosis Model

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

Efficacy of histotripsy combined with rt-PAin vitro

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