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Potentiating intra-arterial sonothrombolysis for acute ischemic stroke by the addition of the ultrasound contrast agents (Optison™ & SonoVue®)

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Abstract

Transcranial ultrasound in combination with intravenously administered ultrasound contrast agents (UCA) in the presence or absence of recombinant tissue plasminogen activator (rt-PA) has been widely evaluated as a new modality for treatment of ischemic stroke. Despite the successful demonstration of accelerated clot lysis there are inherent limitations associated with this modality such as inconsistency in temporal window thickness and/or potential serious cardiopulmonary reactions to intravenous administration of UCA that prevent broad application to ischemic stroke populations. As a complementary modality, we evaluated potential lysis enhancement by intra-arterial ultrasound with concurrent intra-clot delivery of UCA and rt-PA. To this end, clots were formed with average pore diameter similar to clinically retracted clots by adjusting the thrombin concentration. Physical characteristic and retention of UCA after delivery through the catheter as a function of clinically relevant flow rates of 6, 12, 18 ml/h were determined using a microscopic method. The ability of the UCA employed in this study, Optison and SonoVue, to penetrate into the clot was verified using ultrasound B-mode imaging. Clot lysis as a function of rt-PA concentration, 0.009 through 0.5 mg/ml, in the presence and absence of UCA diluted to 1:10, 1:100, and 1:200 v/v at two Peak rarefaction acoustic pressures of 1.3 and 2.1 MPa were evaluated using a weighing method. The study results suggest the addition of only 0.02 ml of 1:100 diluted UCA to rt-PA of 0.009, 0.05, 0.3, and 0.5 mg/ml can enhance the lysis rate by 3.9, 2.6, 1.9 and 1.8 fold in the presence of peak rarefaction acoustic pressure of 1.3 MPa and by 5.1, 3.4, 2.6, 3.1 in the presence of peak rarefaction acoustic pressure of 2.1 MPa, respectively. In addition, Optison and SonoVue demonstrated comparable effectiveness in enhancing the clot lysis rate. Addition of UCA to intra-arterial sonothrombolysis could be considered as a viable treatment option for ischemic stroke patients.

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Acknowledgement

The authors gratefully acknowledge National Institute of Neurological Disorder and Stroke agency (NINDS) at the National Institute of Health (NIH) for funding this research by grant No. 5R21NS053418-02. Its contents are the authors’ sole responsibility and do not necessarily represent the official views of NINDS.

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Authors and Affiliations

  1. Research and Development Department, EKOS Corporation, 11911 North Creek Parkway South, Bothell, WA, 98011, USA

    Azita Soltani, Ruchi Singhal, Melissa Obtera & Douglas R. Hansmann

  2. Department of Mechanical Engineering, Boston University, Boston, MA, USA

    Ronald A. Roy

  3. Oregon Stroke Center, Oregon Health Sciences University, Portland, OR, USA

    Wayne M. Clark

Authors
  1. Azita Soltani
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  2. Ruchi Singhal
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  3. Melissa Obtera
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  4. Ronald A. Roy
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  6. Douglas R. Hansmann
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Correspondence to Azita Soltani.

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Soltani, A., Singhal, R., Obtera, M. et al. Potentiating intra-arterial sonothrombolysis for acute ischemic stroke by the addition of the ultrasound contrast agents (Optison™ & SonoVue®). J Thromb Thrombolysis 31, 71–84 (2011). https://doi.org/10.1007/s11239-010-0483-3

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  • DOI: https://doi.org/10.1007/s11239-010-0483-3

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