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

Azzdine Y. Ammi; Jonathan R. Lindner; Yan Zhao; Thomas Porter; Robert Siegel; Sanjiv Kaul

doi:10.1160/TH14-03-0286

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 113(06): 1357-1369
DOI: 10.1160/TH14-03-0286

Stroke, Systemic or Venous Thromboembolism

Schattauer GmbH

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

Azzdine Y. Ammi

¹Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA

,

Jonathan R. Lindner

¹Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA

,

Yan Zhao

¹Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA

,

Thomas Porter

²Division of Cardiology, University of Nebraska, Omaha, Nebraska, USA

,

Robert Siegel

³Cardiology Division, Cedars Sinai Medical Center, Los Angeles, California, USA

,

Sanjiv Kaul

¹Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA

› Author Affiliations

Abstract

Summary

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.

Supported by grant (NIH R01-HL-095868).

Keywords

Thrombolysis / thrombolytic agents - ultrasound analysis - imaging

Full Text

References

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