Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions: protocol for a phase II single-arm trial

Ebben, Harm P.; Nederhoed, J.H.; Lely, Rutger J.; Wisselink, Willem; Yeung, Kak K.

doi:10.1136/bmjopen-2016-014365

Cited by 21 publications

(16 citation statements)

References 19 publications

(18 reference statements)

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“…12 An ongoing phase II clinical trial is investigating the safety and clinical feasibility of USstimulated MBs for thrombolysis. 13 Additionally, another application arises from the increased frequency of femoral artery puncture to access the vasculature in interventional cardiology and interventional radiology. Perforation to the vessel combined with the influence of arterial pressure can form a perfused blood sac that communicates with the vessel lumen.…”

Section: Clinical Utility Of Therapeutic Microbubblesmentioning

confidence: 99%

An Indispensable tool for ultrasound based diagnostics and therapies - Microbubbles

Thomas¹,

Stride²

2020

JNDS

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Microbubbles (MBs) are micrometre sized gas spheres comprising a biocompatible shell that provide vascular contrast for diagnostic ultrasound (US) imaging. MBs volumetrically oscillate in an ultrasonic field and scatter acoustic energy over a range of frequencies that can be separated from the tissue response. MBs can also provide organ perfusion rates by imaging their “wash-in” to a region of interest which can be correlated to vascular flow. When driven at higher acoustic pressures, localized biological effects can be induced, including increased tissue permeabilization, thermal effects and localised release of drugs that can be encapsulated in the MBs themselves. Both hydrophobic and hydrophilic drugs can be loaded on to MBs e.g. through the use of liposomal carriers or direct attachment of drug molecules to the bubble shell. Since the early 2000s, MB-based technologies have been well researched, though there was significant regulatory push back starting in 2006 based on a controversial clinical trial. From that point, both physicians and researchers have consistently demonstrated the robust safety of MBs as ultrasound contrast agents and their significant clinical utility. Within the last 5 years, more indications have been approved. A recent first-in-man clinical trial of therapeutic US with MBs reversibly opening the blood brain barrier has also been shown to be safe in amyotrophic lateral sclerosis patients. The following article outlines the coupling of US and MBs as a diagnostic and therapeutic platform with a particular focus on their application to the therapy of surgical diseases.

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Section: Clinical Utility Of Therapeutic Microbubblesmentioning

confidence: 99%

An Indispensable tool for ultrasound based diagnostics and therapies - Microbubbles

Thomas¹,

Stride²

2020

JNDS

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“…41 This method proved to be successful in animal models and in a phase II single-arm clinical trial involving patients with acute peripheral arterial occlusions eligible for thrombolytic treatment. 42 Furthermore, preclinical trials have demonstrated that CEUS was suitable to restore epicardial and microvascular flow after ST-segment elevation myocardial infarction (STEMI) in pigs 43 and a phase II clinical trial is ongoing, evaluating the effect of sonothrombolysis after STEMI (NCT03092089). Unfortunately, several clinical trials addressing sonothrombolysis after STEMI 44 or stroke 13 (EudraCT No 201200032341; NCT#01098981) had to be terminated due to vasoconstriction or increased risk of hemorrhage after multiple US applications, respectively.…”

Section: Therapeutic Ceus In Cardiovascular Applicationsmentioning

confidence: 99%

Ultrasound Microbubbles for Diagnosis and Treatment of Cardiovascular Diseases

Rix

Curaj

Liehn

et al. 2019

Semin Thromb Hemost

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Ultrasound (US) imaging of heart and major arteries and veins is among the most frequently used diagnostic techniques applied in humans. Conventional cardiovascular US sessions include anatomical B-mode and functional M-, pulsed-wave- and Doppler mode, which have their limitations in both precise cardiac chambers' delineation and small vessel imaging. The introduction of contrast-enhanced US, employing microbubble suspensions as contrast agent, has enabled a better delineation of heart chambers, the visualization of myocardial microvasculature, and the atherosclerotic plaque neovascularization. Moreover, specific disease-related molecular tracers have been developed by modifying the microbubbles with targeting ligands directed to biological markers exposed to the luminal side of the blood vessels. Microbubble functionalization has enabled in vivo molecular US imaging of various stages of atherosclerosis, from plaque initiation to plaque vulnerability, and neointima formation following revascularization procedures. Furthermore, oscillating microbubbles have been used to mechanically dissolve thrombus material and may act as carriers of drugs and nucleic acids that are released locally by US pulses. This review article summarizes recent advances in functional and molecular US images and discusses therapeutic applications of microbubbles. The addressed topics include an overview on microbubble formats, microbubble detection methods, molecular targets of cardiovascular diseases, and the use of microbubbles for thrombolysis and drug delivery.

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“…Ebben et al elaborated protocol for a phase II single-arm trial for peripheral arterial occlusions. They highlighted safety of the procedure and reduction of major hemorrhagic complications by lowering thrombolytic drug dosage [45]. Whereas Zhu et al did a clinical study on intra-clot microbubble-enhanced ultrasound thrombolysis for deep vein thrombosis.…”

Section: Gliomamentioning

confidence: 99%

Microbubble based sonoporation — from the basics into clinical implications

Wawryka

Iwanek

2019

Medical Research Journal

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Sonoporation is a rapidly developing novel technique serving for drug delivery and non-viral gene therapy. It is based on the interaction between microbubbles located in the surrounding of a cell and its membrane. The interaction is obtained by excitation of microbubbles with ultrasounds. This leads to reversible cell membrane poration. Depending on the intensity of ultrasounds, structure of microbubbles used in an experiment and different environmental factors, microbubbles can interact in two manners. First, in lower ultrasound intensities, stable cavitation-regular microbubbles oscillations due to changes in the environment pressure. Microbubbles have to be very close to a cell membrane, therefore, they are usually targeted to an antigen located on the cell membrane by antibodies. Consequently, microbubbles push and pull on the cell membrane and create microstreaming around it causing its disruption. Second, inertial cavitation, where in contrary to the previous one, oscillations cause rapid collapse of microbubbles, which creates shock waves and microjets for the same purpose. No matter in which manner prorated, cells tend to reseal their disrupted cell membrane. Ca2+ ions play a crucial role in the process as well as endo exocytosis. Sonoporation has proved to be an effective modality against different diseases, including variety of cancer types in of both laboratory and clinical studies.

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Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions: protocol for a phase II single-arm trial

Cited by 21 publications

References 19 publications

An Indispensable tool for ultrasound based diagnostics and therapies - Microbubbles

An Indispensable tool for ultrasound based diagnostics and therapies - Microbubbles

Ultrasound Microbubbles for Diagnosis and Treatment of Cardiovascular Diseases

Microbubble based sonoporation — from the basics into clinical implications

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