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

Saurabh Datta, Constantin C. Coussios, Azzdine Ammi, T. Douglas Mast, Gabrielle M. de Courten-Myers, Christy K. Holland

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

Ultrasound has been shown previously 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 used 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 = 0.85, 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. (E-mail: Christy.Holland@uc.edu).

Original languageEnglish (US)
Pages (from-to)1421-1433
Number of pages13
JournalUltrasound in Medicine and Biology
Volume34
Issue number9
DOIs
StatePublished - Sep 2008
Externally publishedYes

Fingerprint

Tissue Plasminogen Activator
cavitation flow
nucleation
Plasminogen
Pressure
Microbubbles
Fibrinolytic Agents
Optical Imaging
penetration
Netherlands
Contrast Media
Thrombosis
Definity
hydrophones
antibodies
imaging techniques
Antibodies
blood
broadband
harmonics

Keywords

  • Stable cavitation
  • Stroke therapy
  • Therapeutic ultrasound
  • Ultraharmonics
  • Ultrasound-assisted thrombolysis

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Datta, S., Coussios, C. C., Ammi, A., Mast, T. D., de Courten-Myers, G. M., & Holland, C. K. (2008). Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent. Ultrasound in Medicine and Biology, 34(9), 1421-1433. https://doi.org/10.1016/j.ultrasmedbio.2008.01.016

Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent. / Datta, Saurabh; Coussios, Constantin C.; Ammi, Azzdine; Mast, T. Douglas; de Courten-Myers, Gabrielle M.; Holland, Christy K.

In: Ultrasound in Medicine and Biology, Vol. 34, No. 9, 09.2008, p. 1421-1433.

Research output: Contribution to journalArticle

Datta, S, Coussios, CC, Ammi, A, Mast, TD, de Courten-Myers, GM & Holland, CK 2008, 'Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent', Ultrasound in Medicine and Biology, vol. 34, no. 9, pp. 1421-1433. https://doi.org/10.1016/j.ultrasmedbio.2008.01.016
Datta, Saurabh ; Coussios, Constantin C. ; Ammi, Azzdine ; Mast, T. Douglas ; de Courten-Myers, Gabrielle M. ; Holland, Christy K. / Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent. In: Ultrasound in Medicine and Biology. 2008 ; Vol. 34, No. 9. pp. 1421-1433.
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abstract = "Ultrasound has been shown previously 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{\circledR}, 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 used to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity{\circledR} 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{\circledR}. A significant correlation was observed between mass loss and ultraharmonic signals (r = 0.85, 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. (E-mail: Christy.Holland@uc.edu).",
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