Efficacy and spatial distribution of ultrasound-mediated clot lysis in the absence of thrombolytics

Azzdine Ammi, Jonathan Lindner, Yan Zhao, Thomas Porter, Robert Siegel, Sanjiv Kaul

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    Ultrasound and microbubble (MB) contrast agents accelerate clot lysis, yet clinical trials have been performed without defining optimal acoustic conditions. Our aim was to assess the effect of acoustic pressure and frequency on the extent and spatial location of clot lysis. Clots from porcine blood were created with a 2-mm central lumen for infusion of lipid-shelled perfluorocarbon MBs (1×107 ml-1) or saline. Therapeutic ultrasound at 0.04, 0.25, 1.05, or 2.00 MHz was delivered at a wide range of peak rarefactional acoustic pressure amplitudes (PRAPAs). Ultrasound was administered over 20 minutes grouped on-off cycles to allow replenishment of MBs. The region of lysis was quantified using contrast-enhanced ultrasound imaging. In the absence of MBs, sonothrombolysis did not occur at any frequency. Sonothrombolysis was also absent in the presence of MBs despite their destruction at 0.04 and 2.00 MHz. It occurred at 0.25 and 1.05 MHz in the presence of MBs for PRAPAs > 1.2 MPa and increased with PRAPA. At 0.25 MHz the clot lysis was located in the far wall. At 1.05 MHz, however, there was a transition from far to near wall as PRAPA was increased. The area of clot lysis measured by ultrasound imaging correlated with that by micro-CT and quantification of debris in the effluent. In conclusion, sonothrombolysis with MBs was most efficient at 0.25 MHz. The spatial location of sonothrombolysis varies with pressure and frequency indicating that the geometric relation between therapeutic probe and vascular thrombosis is an important variable for successful lysis clinically.

    Original languageEnglish (US)
    Pages (from-to)1357-1369
    Number of pages13
    JournalThrombosis and Haemostasis
    Volume113
    Issue number6
    DOIs
    StatePublished - 2015

    Fingerprint

    Acoustics
    Pressure
    Ultrasonography
    Thrombosis
    Fluorocarbons
    Microbubbles
    Contrast Media
    Blood Vessels
    Swine
    Clinical Trials
    Lipids
    Therapeutics

    Keywords

    • Imaging
    • Thrombolysis/thrombolytic agents
    • Ultrasound analysis

    ASJC Scopus subject areas

    • Hematology

    Cite this

    Efficacy and spatial distribution of ultrasound-mediated clot lysis in the absence of thrombolytics. / Ammi, Azzdine; Lindner, Jonathan; Zhao, Yan; Porter, Thomas; Siegel, Robert; Kaul, Sanjiv.

    In: Thrombosis and Haemostasis, Vol. 113, No. 6, 2015, p. 1357-1369.

    Research output: Contribution to journalArticle

    Ammi, Azzdine ; Lindner, Jonathan ; Zhao, Yan ; Porter, Thomas ; Siegel, Robert ; Kaul, Sanjiv. / Efficacy and spatial distribution of ultrasound-mediated clot lysis in the absence of thrombolytics. In: Thrombosis and Haemostasis. 2015 ; Vol. 113, No. 6. pp. 1357-1369.
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    AU - Siegel, Robert

    AU - Kaul, Sanjiv

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    N2 - Ultrasound and microbubble (MB) contrast agents accelerate clot lysis, yet clinical trials have been performed without defining optimal acoustic conditions. Our aim was to assess the effect of acoustic pressure and frequency on the extent and spatial location of clot lysis. Clots from porcine blood were created with a 2-mm central lumen for infusion of lipid-shelled perfluorocarbon MBs (1×107 ml-1) or saline. Therapeutic ultrasound at 0.04, 0.25, 1.05, or 2.00 MHz was delivered at a wide range of peak rarefactional acoustic pressure amplitudes (PRAPAs). Ultrasound was administered over 20 minutes grouped on-off cycles to allow replenishment of MBs. The region of lysis was quantified using contrast-enhanced ultrasound imaging. In the absence of MBs, sonothrombolysis did not occur at any frequency. Sonothrombolysis was also absent in the presence of MBs despite their destruction at 0.04 and 2.00 MHz. It occurred at 0.25 and 1.05 MHz in the presence of MBs for PRAPAs > 1.2 MPa and increased with PRAPA. At 0.25 MHz the clot lysis was located in the far wall. At 1.05 MHz, however, there was a transition from far to near wall as PRAPA was increased. The area of clot lysis measured by ultrasound imaging correlated with that by micro-CT and quantification of debris in the effluent. In conclusion, sonothrombolysis with MBs was most efficient at 0.25 MHz. The spatial location of sonothrombolysis varies with pressure and frequency indicating that the geometric relation between therapeutic probe and vascular thrombosis is an important variable for successful lysis clinically.

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