Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz

Everbach, E. Carr; Francis, Charles W.

doi:10.1016/s0301-5629(00)00250-7

Cited by 161 publications

(111 citation statements)

References 38 publications

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“…Several mechanistic in vitro studies have been conducted to investigate the interaction of US with thrombolytic drugs , Blinc et al 1993, Francis 1995, Suchkova et al 1998, Akiyama et al 1998, Behrens et al 1999, Everbach et al 2000, Holland et al 2007. Some of these studies have shown that US potentiation of fibrinolysis is related to increased transport of reactants through cavitation-related mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…This was experimentally demonstrated by Blinc et al (1992). In several mechanistic in vitro studies it is speculated that US facilitates transport of fibrinolytic enzymes into the clot (Francis et al 1995;Pieters et al 2004;Devcic-Kuhar et al 2004) along with mechanical effects like microstreaming (Sakharov et al 2000) and acoustic cavitation (Everbach and Francis 2000;Datta et al 2005Datta et al , 2006Prokop et al 2007) among other possible mechanisms. Tachibana and Tachibana (1995) introduced the use of microbubbles to augment thrombolysis using 170-kHz US adjuvant to urokinase in an in vitro human blood clot model.…”

Section: Introductionmentioning

confidence: 95%

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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%

Section: Introductionmentioning

confidence: 95%

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

Datta

Coussios

Ammi

et al. 2008

Ultrasound in Medicine & Biology

228

200

View full text Add to dashboard Cite

show abstract

“…Careful investigations by Francis et al suggest that ultrasound accelerates enzymatic fibrinolysis by increasing transport of reactants through a cavitation-related mechanism [16][17][18]. However, experiments employing ultrasound exposure of clots in a hyperbaric chamber revealed that other mechanisms in addition to inertial cavitation were present [19]. Several investigators have utilized low-frequency, low-intensity ultrasound to accelerate rt-PA thrombolysis in vitro [20,21].…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model

Holland

Vaidya

Datta

et al. 2008

Thrombosis Research

100

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“…Ultrasound thermal ablation uses the energy in the ultrasound waves to heat and kill targeted tissue and has been extensively studied [2][3][4][5][6][7][8][9][10][11][12][13][14]. In addition to killing tissue, ultrasound therapies are being successfully developed to enhance thrombolysis [15,16], improve drug and gene delivery [17][18][19][20][21][22], control bleeding and hemorrhaging from severe trauma [13,24], and erode or liquefy tissue by controlled technique [7,[25][26][27][28][29][30]. Many of these developing therapies have been found to depend upon or be significantly enhanced by the cavitation of microbubbles.…”

Section: Introductionmentioning

confidence: 99%

Dependence of Cavitation Bubble Size on Pressure Amplitude at Therapeutic Levels

Carvell¹,

Bigelow²

2009

AIP Conference Proceedings

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High-intensity, focused ultrasound therapy is a minimally invasive therapy technique that is effective and relatively safe. It can be used in areas including histotripsy, thermal ablation, and administering medication. Inertial cavitation is used to improve these therapy methods. The purpose of this study was to determine the effect of pressure amplitude on cavitation resonance frequency/bubble size at therapeutic field levels. Earlier work has indicated that the resonance size depends on pressure amplitude; however, the investigation only considered pressure amplitudes up to 1 MPa [1]. Our study was conducted by simulating the response of bubbles to linearly propagating sine waves using the Gilmore-Akulichev formulation to solve for the bubble response. The frequency of the sine wave varied from 1 to 5 MHz while the amplitude of the sine wave varied from 0.0001 to 9 MPa. The resonance size for a particular frequency of excitation and amplitude was determined by finding the initial bubble size that resulted in the maximum bubble expansion for an air bubble in water. The simulations demonstrated a downshift in resonance size with increasing pressure amplitude. Therefore, smaller bubbles will have a more dramatic response to ultrasound at therapeutic levels. KeywordsBubble dynamics, cavitation, therapeutics, high pressure, sound pressure Disciplines Biomedical | Biomedical Devices and Instrumentation | Electrical and Computer Engineering CommentsThe following article appeared in AIP Conference Proceedings 1113 (2009) Abstract High-intensity, focused ultrasound therapy is a minimally invasive therapy technique that is effective and relatively safe. It can be used in areas including histotripsy, thermal ablation, and administering medication. Inertial cavitation is used to improve these therapy methods. The purpose of this study was to determine the effect of pressure amplitude on cavitation resonance frequency/bubble size at therapeutic field levels. Earlier work has indicated that the resonance size depends on pressure amplitude; however, the investigation only considered pressure amplitudes up to 1 MPa [1]. Our study was conducted by simulating the response of bubbles to linearly propagating sine waves using the Gilmore-Akulichev formulation to solve for the bubble response. The frequency of the sine wave varied from 1 to 5 MHz while the amplitude of the sine wave varied from 0.0001 to 9 MPa. The resonance size for a particular frequency of excitation and amplitude was determined by finding the initial bubble size that resulted in the maximum bubble expansion for an air bubble in water. The simulations demonstrated a downshift in resonance size with increasing pressure amplitude. Therefore, smaller bubbles will have a more dramatic response to ultrasound at therapeutic levels..

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Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz

Cited by 161 publications

References 38 publications

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

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

Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model

Dependence of Cavitation Bubble Size on Pressure Amplitude at Therapeutic Levels

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