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

Azita Soltani, Ruchi Singhal, Melissa Obtera, Ronald A. Roy, Wayne Clark, Douglas R. Hansmann

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)71-84
Number of pages14
JournalJournal of Thrombosis and Thrombolysis
Volume31
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Contrast Media
Stroke
Tissue Plasminogen Activator
Acoustics
Pressure
contrast agent BR1
FS 069
Thrombin
Intravenous Administration
Catheters
Therapeutics
Population

Keywords

  • Acute ischemic stroke
  • Intra-arterial treatment
  • Microbubbles
  • Optison™
  • Sonothrombolysis
  • SonoVue

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Potentiating intra-arterial sonothrombolysis for acute ischemic stroke by the addition of the ultrasound contrast agents (Optison™ & SonoVue®). / Soltani, Azita; Singhal, Ruchi; Obtera, Melissa; Roy, Ronald A.; Clark, Wayne; Hansmann, Douglas R.

In: Journal of Thrombosis and Thrombolysis, Vol. 31, No. 1, 01.2011, p. 71-84.

Research output: Contribution to journalArticle

Soltani, Azita ; Singhal, Ruchi ; Obtera, Melissa ; Roy, Ronald A. ; Clark, Wayne ; Hansmann, Douglas R. / Potentiating intra-arterial sonothrombolysis for acute ischemic stroke by the addition of the ultrasound contrast agents (Optison™ & SonoVue®). In: Journal of Thrombosis and Thrombolysis. 2011 ; Vol. 31, No. 1. pp. 71-84.
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