Tissue Plasminogen Activator Concentration Dependence of 120 kHz Ultrasound-Enhanced Thrombolysis

Shaw, George J.; Meunier, Jason M.; Lindsell, Christopher J.; Holland, Christy K.

doi:10.1016/j.ultrasmedbio.2008.03.020

Cited by 26 publications

(40 citation statements)

References 56 publications

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“…C in an open container for 2 h. Human clots were manufactured around silk sutures following the protocol developed by Shaw et al (2008). Following local institutional review board approval, and written informed consent, human whole blood was drawn from a pool of volunteers.…”

Section: A Human Plasma and Clotsmentioning

confidence: 99%

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Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

Gruber

Bader

Holland

2014

The Journal of the Acoustical Society of America

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Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity V R ) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540-900 kHz) and a broad frequency bandwidth (0.54-1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 6 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle.

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Section: A Human Plasma and Clotsmentioning

confidence: 99%

“…Ultrasound-enhanced thrombolysis (UET) is under development as an adjuvant to rt-PA (Akiyama et al, 1998;Shaw et al, 2008Shaw et al, , 2009. Ultrasound contrast agents (UCAs) are stabilized microbubbles that can be injected into the bloodstream and have previously been used to nucleate acoustic cavitation (Rota et al, 2006;Sboros, 2008).…”

Section: Introductionmentioning

confidence: 99%

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

Gruber

Bader

Holland

2014

The Journal of the Acoustical Society of America

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“…[1][2][3][4][5] At sufficient acoustic pressure, MBs will rupture, causing local fluid microjetting, which can result in pitting on solid surfaces, and may be responsible for enhancing thrombus fragmentation. 6,7 Additionally, microstreaming resulting from MB oscillation in an US field may enhance the penetration of fibrinolytic enzymes such as rt-PA into the structure of the thrombus.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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Abstract. Several in vitro and in vivo studies have established accelerated thrombolysis using ultrasound (US) induced microbubble (MB) cavitation. However, the mechanisms underlying MB mediated sonothrombolysis are still not completely elucidated. We performed three-dimensional (3-D) volumetric optical coherence tomography (OCT) imaging before and after the application of contrast US to thrombus. The most dramatic reduction in clot volume was observed with US + MB + recombinant tissue plasminogen activator (rt-PA). Thrombus surface erosion in this group on the side of the thrombus exposed to MB and ultrasound was evident on the OCT images. This technique may assist in clarifying the mechanisms underlying sonothrombolysis, especially regarding the importance of US transducer orientation on lytic efficacy and the effects of MB cavitation on thrombus structure.

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“…During the past few years, treatment of ischemic stroke using ultrasound has received great attention [10][11][12][13][14][15]. Most previous studies have used unfocused ultrasound at very low intensities.…”

Section: Introductionmentioning

confidence: 99%

“…Most previous studies have used unfocused ultrasound at very low intensities. Several experimental studies have been performed to investigate the effectiveness of sonothrombolysis with, and without, thrombolytic drugs (such as Recombinant Tissue-Type Plasminogen Activator) [1,[10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Temperature estimation of focused ultrasound exposures for stroke treatment

Hadjisavvas¹,

Damianou²

2011

JBiSE

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Introduction: in this paper a simulation model for predicting the temperature during the application of focused ultrasound (FUS) for stroke treatment using pulsed ultrasound is presented. Materials and methods: a single element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at either 0.5 MHz or 1 MHz was considered. The power field was estimated using the Khokhlov-Zabolotskaya-Kuznetzov (KZK) model. The temperature was estimated using the bioheat equation. The goal was to extract the acoustic parameters (frequency, power, and duty factor) that maintain a temperature increase of less than 1˚C during the application of a pulse ultrasound protocol. Results: it was found that the temperature change increases linearly with duty factor. The higher the power, the lower the duty factor needed to keep the temperature change to the safe limit of 1˚C. The higher the frequency the lower the duty factor needed to keep the temperature change to the safe limit of 1˚C. Finally, the shallow the target, the lower the duty factor needed to keep the temperature change to the safe limit of 1˚C. The simulation model was tested in brain tissue during the application of pulse ultrasound and the measured temperature was in close agreement with the simulated temperature. Conclusions: This simulation model is considered to be very useful tool for providing acoustic parameters (frequency, power, and duty factor) during the application of pulsed ultrasound at various depths in tissue so that a safe temperature is maintained during the treatment. This model will be tested eventually during stroke clinical trials.

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Tissue Plasminogen Activator Concentration Dependence of 120 kHz Ultrasound-Enhanced Thrombolysis

Cited by 26 publications

References 56 publications

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

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

Temperature estimation of focused ultrasound exposures for stroke treatment

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