Intravascular forward-looking ultrasound transducers for microbubble-mediated sonothrombolysis

Kim, Jin-Wook; Lindsey, Brooks D.; Chang, Wei Yi; Dai, Xuming; Stavas, Joseph M.; Dayton, Paul A.; Jiang, Xiaoning

doi:10.1038/s41598-017-03492-4

Cited by 71 publications

(53 citation statements)

References 54 publications

(58 reference statements)

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“…Ultrasonic energy may be delivered to infected areas either extracorporeally or using catheter-based ultrasound probes. Catheters have been reported previously for sonothrombolysis (Owens 2008;Kim et al 2017), and could be investigated for sonobactericide in vascular organs.…”

Section: Clinical Translation Of Sonobactericidementioning

confidence: 99%

Sonobactericide: An Emerging Treatment Strategy for Bacterial Infections

Lattwein

Shekhar

Kouijzer

et al. 2020

Ultrasound in Medicine & Biology

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Ultrasound has been developed as both a diagnostic tool and a potent promoter of beneficial bioeffects for the treatment of chronic bacterial infections. Bacterial infections, especially those involving biofilm on implants, indwelling catheters and heart valves, affect millions of people each year, and many deaths occur as a consequence. Exposure of microbubbles or droplets to ultrasound can directly affect bacteria and enhance the efficacy of antibiotics or other therapeutics, which we have termed sonobactericide. This review summarizes investigations that have provided evidence for ultrasound-activated microbubble or droplet treatment of bacteria and biofilm. In particular, we review the types of bacteria and therapeutics used for treatment and the in vitro and pre-clinical experimental setups employed in sonobactericide research. Mechanisms for ultrasound enhancement of sonobactericide, with a special emphasis on acoustic cavitation and radiation force, are reviewed, and the potential for clinical translation is discussed. (

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Section: Clinical Translation Of Sonobactericidementioning

confidence: 99%

Sonobactericide: An Emerging Treatment Strategy for Bacterial Infections

Lattwein

Shekhar

Kouijzer

et al. 2020

Ultrasound in Medicine & Biology

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“…One study again uses the EKOS system, which is a side-viewing low power, high frequency transducer, and demonstrates that this device is able to improve clot lysis outcomes with tPA and microbubble mediated sonothrombolysis in an in vitro deep vein thrombosis model [115]. Another study from our research group developed a forward viewing, sub-megahertz intravascular transducer for sonothrombolysis treatment which aims to be applied for deep vein thrombosis [116]. These parameters were optimized for microbubble mediated sonothrombolysis without the need for a thrombolytic agent, and in vitro studies have shown great success in treating blood clots with this technique.…”

Section: Intravascular Sonothrombolysismentioning

confidence: 99%

Advances in Sonothrombolysis Techniques Using Piezoelectric Transducers

Goel

Jiang

2020

Sensors

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One of the great advancements in the applications of piezoelectric materials is the application for therapeutic medical ultrasound for sonothrombolysis. Sonothrombolysis is a promising ultrasound based technique to treat blood clots compared to conventional thrombolytic treatments or mechanical thrombectomy. Recent clinical trials using transcranial Doppler ultrasound, microbubble mediated sonothrombolysis, and catheter directed sonothrombolysis have shown promise. However, these conventional sonothrombolysis techniques still pose clinical safety limitations, preventing their application for standard of care. Recent advances in sonothrombolysis techniques including targeted and drug loaded microbubbles, phase change nanodroplets, high intensity focused ultrasound, histotripsy, and improved intravascular transducers, address some of the limitations of conventional sonothrombolysis treatments. Here, we review the strengths and limitations of these latest pre-clincial advancements for sonothrombolysis and their potential to improve clinical blood clot treatments.

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“…Thus, it was important to evaluate the feasibility of miniaturizing the FFMD to human-compatible dimensions. The catheter-based design is also intended for integration onto a catheter that emits therapeutic levels of ultrasound energy via either a forward-looking 44 or radially-emitting ultrasound transducer 45 and contains on-chip sensors for real-time monitoring and control of microbubble production rate and diameter. 46 The present study focused on ischemic stroke, but a multi-function sonothrombolysis catheter could find application in stroke, deep vein thrombosis, myocardial infarction, and other thrombosis-related conditions including those pertaining to the microvasculature.…”

Section: Miniaturization Of Ffmds To Human-compatible Dimensionsmentioning

confidence: 99%

Efficacy of Sonothrombolysis Using Microbubbles Produced by a Catheter-Based Microfluidic Device in a Rat Model of Ischemic Stroke

Dixon

Rickel

et al. 2019

Ann Biomed Eng

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Limitations of existing thrombolytic therapies for acute ischemic stroke have motivated the development of catheter-based approaches that utilize no or low doses of thrombolytic drugs combined with a mechanical action to either dissolve or extract the thrombus. Sonothrombolysis accelerates thrombus dissolution via the application of ultrasound combined with microbubble contrast agents and low doses of thrombolytics to mechanically disrupt the fibrin mesh. In this work, we studied the efficacy of catheter-directed sonothrombolysis in a rat model of ischemic stroke. Microbubbles of 10-20 μm diameter with a nitrogen gas core and a non-crosslinked albumin shell were produced by a flow-focusing microfluidic device in real time. The microbubbles were dispensed from a catheter located in the internal carotid artery for direct delivery to the thrombus-occluded middle cerebral artery, while ultrasound was administered through the skull and recombinant tissue plasminogen activator (rtPA) was infused via a tail vein catheter. The results of this study demonstrate that flow focusing microfluidic devices can be miniaturized to dimensions compatible with human catheterization and that large-diameter microbubbles comprised of high solubility gases can be safely administered intraarterially to deliver a sonothrombolytic therapy. Further, sonothrombolysis using intraarterial delivery of large microbubbles reduced cerebral infarct volumes by approximately 50% versus no therapy, significantly improved functional neurological outcomes at 24 hrs, and permitted rtPA dose reduction of 3.3 (95% C.I. 1.8-3.8) fold when compared to therapy with intravenous rtPA alone. Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. https://www.springer.com/aamterms-v1 Author Contributions Statement AJD, JAH, ZZ conceived of study. AJD wrote main manuscript text. AJD, JMRR, JL conducted experiments and analyzed data. JAH, ALK, and ZZ supervised the study and all authors reviewed the manuscript.

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Intravascular forward-looking ultrasound transducers for microbubble-mediated sonothrombolysis

Cited by 71 publications

References 54 publications

Sonobactericide: An Emerging Treatment Strategy for Bacterial Infections

Sonobactericide: An Emerging Treatment Strategy for Bacterial Infections

Advances in Sonothrombolysis Techniques Using Piezoelectric Transducers

Efficacy of Sonothrombolysis Using Microbubbles Produced by a Catheter-Based Microfluidic Device in a Rat Model of Ischemic Stroke

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