Volumetric quantification of<i>in vitro</i>sonothrombolysis with microbubbles using high-resolution optical coherence tomography

Kim, Jong Seung; Leeman, Jonathan E.; Kagemann, Larry; Yu, François T.H.; Chen, Xucai; Pacella, John J.; Schuman, Joel S.; Villanueva, Flordeliza S.; Kim, Kang

doi:10.1117/1.jbo.17.7.070502

Cited by 9 publications

(5 citation statements)

References 14 publications

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“…Microjets may erode the clot surface to cause disruption of clot integrity, and secondary bubbles may themselves oscillate and create more jets (Chen et al 2014). Our own group has previously reported that microbubbles flowing past a thrombus in the presence of inertial cavitation ultrasound regime cause clot pitting in vitro (Kim et al 2012). Further, using ultra-high-speed imaging (Chen et al 2013), we have recently observed in vitro that inertial cavitation behavior of microbubbles adjacent to a clot alternately invaginates and stretches the thrombus, ultimately leaving indentations in the thrombus after microbubble destruction (Chen et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Microvascular Micro-embolization Using Microbubbles and Long-Tone-Burst Ultrasound: An in Vivo Study

Pacella

Brands

Schnatz

et al. 2015

Ultrasound in Medicine & Biology

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Despite epicardial coronary artery reperfusion by percutaneous coronary intervention, distal micro-embolization into the coronary microcirculation limits myocardial salvage during acute myocardial infarction. Thrombolysis using ultrasound and microbubbles (sonothrombolysis) is an approach that induces microbubble oscillations to cause clot disruption and restore perfusion. We sought to determine whether this technique could restore impaired tissue perfusion caused by thrombotic microvascular obstruction. In 16 rats, an imaging transducer was placed on the biceps femoris muscle, perpendicular to a single-element 1-MHz treatment transducer. Ultrasound contrast perfusion imaging was performed at baseline and after micro-embolization. Therapeutic ultrasound (5000 cycles, pulse repetition frequency = 5 0.33 Hz, 1.5 MPa) was delivered to nine rats for two 10-min sessions during intra-arterial infusion of lipid-encapsulated microbubbles; seven control rats received no ultrasound–microbubble therapy. Ultrasound contrast perfusion imaging was repeated after each treatment or control period, and microvascular volume was measured as peak video intensity. There was a 90% decrease in video intensity after micro-embolization (from 8.6 ± 4.8 to 0.7 ± 0.8 dB, p < 0.01). The first and second ultrasound–microbubble sessions were respectively followed by video intensity increases of 5.8 ± 5.1 and 8.7 ± 5.7 dB (p < 0.01, compared with micro-embolization). The first and second control sessions, respectively, resulted in no significant increase in video intensity (2.4 ± 2.3 and 3.6 ± 4.9) compared with micro-embolization (0.6 ± 0.7 dB). We have developed an in vivo model that simulates the distal thrombotic microvascular obstruction that occurs after primary percutaneous coronary intervention. Long-pulse-length ultrasound with microbubbles has a therapeutic effect on microvascular perfusion and may be a valuable adjunct to reperfusion therapy for acute myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Treatment of Microvascular Micro-embolization Using Microbubbles and Long-Tone-Burst Ultrasound: An in Vivo Study

Pacella

Brands

Schnatz

et al. 2015

Ultrasound in Medicine & Biology

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“…The degree of clot retraction can be modified by altering the properties of the surface in contact with incubated blood (Sutton et al 2013b), or by storing the clot at low temperatures (<4 °C) for several days post-incubation (Shaw et al 2006). Thrombolytic metrics have included mass loss (Datta et al 2006), dimensional reduction on an image (Cheng et al 2005; Kim et al 2012; Petit et al 2012a), or the presence of fibrin degradation products (Francis et al 1992; Kimura et al 1994; Pfaffenberger et al 2003; Alonso et al 2009). Interested readers are invited to review an exhaustive list of recent in-vitro studies compiled by Petit et al (2012b).…”

Section: 3 Experimental Evidence For Ultrasound-enhanced Efficacymentioning

confidence: 99%

Sonothrombolysis

Bader¹,

Bouchoux²,

Holland³

2016

Advances in Experimental Medicine and Biology

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Thrombo-occlusive disease is a leading cause of morbidity and mortality. In this chapter, the use of ultrasound to accelerate clot breakdown alone or in combination with thrombolytic drugs will be reported. Primary thrombus formation during cardiovascular disease and standard treatment methods will be discussed. Mechanisms for ultrasound enhancement of thrombolysis, including thermal heating, radiation force, and cavitation, will be reviewed. Finally, in-vitro, in-vivo and clinical evidence of enhanced thrombolytic efficacy with ultrasound will be presented and discussed.

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“…MB cavitation induced by US is thought to be a major mechanism of sonothrombolysis, where clot disruption is accelerated by US activated MBs through direct mechanical force (Kim et al 2012; Chen et al 2014) or enhanced material transport (Datta et al 2008). MB cavitation is also mechanistically involved in sonoporation, where transient pores in the plasma membrane are formed to allow therapeutic loads to cross the cell membrane (Qin et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Dynamic Behavior of Microbubbles during Long Ultrasound Tone-Burst Excitation: Mechanistic Insights into Ultrasound-Microbubble Mediated Therapeutics Using High-Speed Imaging and Cavitation Detection

Chen

Wang

Pacella

et al. 2016

Ultrasound in Medicine & Biology

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Ultrasound (US)-microbubble (MB) mediated therapies have been shown to restore perfusion and enhance drug/gene delivery. Due to the presumption that MBs do not persist during long US exposure under high acoustic pressures, most schemes utilize short US pulses when a high US pressure is employed. However, we recently observed an enhanced thrombolytic effect using long US pulses at high acoustic pressures. Therefore we explored the fate of MBs during long tone-burst exposures (5 ms) at various acoustic pressures and MB concentrations via direct high-speed optical observation and passive cavitation detection. MBs first underwent stable or inertial cavitation depending on the acoustic pressure, and then formed gas-filled clusters that continued to oscillate, break up, and form new clusters. Cavitation detection confirmed continued, albeit diminishing acoustic activity throughout the 5-ms US excitation. These data suggest that persisting cavitation activity during long tone-bursts may confer additional therapeutic effects.

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Volumetric quantification ofin vitrosonothrombolysis with microbubbles using high-resolution optical coherence tomography

Cited by 9 publications

References 14 publications

Treatment of Microvascular Micro-embolization Using Microbubbles and Long-Tone-Burst Ultrasound: An in Vivo Study

Treatment of Microvascular Micro-embolization Using Microbubbles and Long-Tone-Burst Ultrasound: An in Vivo Study

Sonothrombolysis

Dynamic Behavior of Microbubbles during Long Ultrasound Tone-Burst Excitation: Mechanistic Insights into Ultrasound-Microbubble Mediated Therapeutics Using High-Speed Imaging and Cavitation Detection

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