Enhancement of ultrasound-accelerated thrombolysis by echo contrast agents: dependence on microbubble structure

Mizushige, Katsufumi; Kondô, Isao; Ohmori, Koji; Hirao, Kenichi; Matsuo, Hirohíde

doi:10.1016/s0301-5629(99)00095-2

Cited by 90 publications

(52 citation statements)

References 25 publications

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“…Earlier Porter et al (1996) observed thrombolytic enhancement in vitro using perfluorocarbon-exposed sonicated dextrose albumin microbubbles together with 20-kHz US (0.845 MPa peak negative pressure amplitude) and urokinase. Along the same lines, Mizushige et al (1999) compared different contrast agents used with rt-PA and catheter-based 10-MHz US. They reported a correlation between the persistence of microbubbles during the US exposure and thrombolysis in their in vitro experiments.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent

Datta

Coussios

Ammi

et al. 2008

Ultrasound in Medicine & Biology

228

200

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Ultrasound has been previously shown to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity ® , was used to promote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions, and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and utilized to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity ® , and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120 kHz ultrasound (0.32 MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity ® . A significant correlation was observed between mass loss and ultraharmonic signals (r=0.8549, p<0.0001, n=24). The largest mean penetration depth of rt-PA (222 µm) and plasminogen (241 µm) was observed in the presence of stable cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment.

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Section: Discussionmentioning

confidence: 99%

Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent

Datta

Coussios

Ammi

et al. 2008

Ultrasound in Medicine & Biology

228

200

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“…Experimental studies have shown that US-accelerated thrombolysis may be further enhanced by administration of MBs. [3][4][5][6] Low-frequency US with high power has been demonstrated to produce cavitation and fluid motion into the thrombus. 4,5 MBs, by acting as cavitation nuclei, lower the amount of energy needed for cavitation.…”

Section: T He Combined Lysis Of Thrombus In Brain Ischemia Usingmentioning

confidence: 99%

“…[3][4][5][6] Low-frequency US with high power has been demonstrated to produce cavitation and fluid motion into the thrombus. 4,5 MBs, by acting as cavitation nuclei, lower the amount of energy needed for cavitation. Application of high-acoustic-pressure US has been shown to induce nonlinear oscillations of MBs, leading to a continuous absorption of energy until the bubbles explode, releasing the absorbed energy.…”

Section: T He Combined Lysis Of Thrombus In Brain Ischemia Usingmentioning

confidence: 99%

Microbubble Administration Accelerates Clot Lysis During Continuous 2-MHz Ultrasound Monitoring in Stroke Patients Treated With Intravenous Tissue Plasminogen Activator

Molina

Ribó

Rubiera

et al. 2006

Stroke

428

298

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“…The addition of intravenously injected microbubbles can enhance the effects of ultrasound and reduce the required energy for producing ultrasound-mediated thrombolysis by decreasing cavitation threshold. 3,12,14,15 Also, a few of studies 16 have shown that HIFU can improve thrombolysis while applying thrombolytic agents by reducing the dosage of the drug and reducing the risk of hemorrhagic events, but increasing its efficacy. In addition, microbubbles and thrombolytic drugs can be combined together for targeted drug delivery, drug transport acceleration [17][18][19][20][21] and eventually enhancing thrombolysis.…”

Section: Introductionmentioning

confidence: 99%

Laser enhanced high-intensity focused ultrasound thrombolysis: An in vitro study

Cui¹,

Yang²

2013

The Journal of the Acoustical Society of America

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Laser-enhanced thrombolysis by high intensity focused ultrasound (HIFU) treatment was studied in vitro with bovine blood clots. To achieve laser-enhanced thrombolysis, laser light was employed to illuminate the sample concurrently with HIFU radiation, and ultrasound and laser parameters were optimized to achieve better thrombolysis efficiency. The results indicated that the thrombolysis efficiency increased when pulse length of HIFU wave, HIFU pressure, or laser fluence increases. Also, with the presence of laser, an enhanced effect of thrombolysis was observed.

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Enhancement of ultrasound-accelerated thrombolysis by echo contrast agents: dependence on microbubble structure

Cited by 90 publications

References 25 publications

Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent

Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent

Microbubble Administration Accelerates Clot Lysis During Continuous 2-MHz Ultrasound Monitoring in Stroke Patients Treated With Intravenous Tissue Plasminogen Activator

Laser enhanced high-intensity focused ultrasound thrombolysis: An in vitro study

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