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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
1   Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA
,
Jonathan R. Lindner
1   Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA
,
Yan Zhao
1   Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA
,
Thomas Porter
2   Division of Cardiology, University of Nebraska, Omaha, Nebraska, USA
,
Robert Siegel
3   Cardiology Division, Cedars Sinai Medical Center, Los Angeles, California, USA
,
Sanjiv Kaul
1   Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA
› Author Affiliations
Further Information

Publication History

Received: 14 April 2014

Accepted after major revision: 17 January 2015

Publication Date:
18 November 2017 (online)

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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
 

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