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  • Title: Intra-arterial administration of microbubbles and continuous 2-MHz ultrasound insonation to enhance intra-arterial thrombolysis.
    Author: Ribo M, Molina CA, Alvarez B, Rubiera M, Alvarez-Sabin J, Matas M.
    Journal: J Neuroimaging; 2010 Jul; 20(3):224-7. PubMed ID: 19226340.
    Abstract:
    BACKGROUND: Microbubbles (MB) and ultrasound have been shown to enhance thrombolysis. We sought to evaluate safety and efficacy on middle cerebral artery (MCA) recanalization of local MB administration during intra-arterial (IA) thrombolysis and continuous transcranial Doppler (TCD) monitoring. METHODS: Patients with acute M1-MCA occlusion were treated with intravenous tissue plasminogen activator (iv-tPA) and continuously monitored with TCD. If recanalization was not achieved during first-hour bridging IA-rescue was adopted: MB + tPA direct intraclot microcatheter infusion. TCD flow monitoring allowed continuous insonation at clot location. Recanalization was angiographically assessed (thrombolysis in cerebral infarction [TICI] score) and compared with simultaneous TCD data. IA procedures were stopped at 6 hours. Recanalization was reassessed at 12 hours (TCD). Neurological status was repeatedly assessed (National Institutes of Health Stroke Scale [NIHSS]). At three months, patients were considered independent if mRS <or= 2. RESULTS: Of the 18 included patients (mean age 72), 16 received standard iv-tPA (.9 mg/kg). Nine patients were recanalized during tPA infusion and 9 patients underwent IA-rescue procedures. Median pre-IA NIHSS score: 20. Median time to IA initiation was 175 +/- 63 minutes. Mean IA doses were tPA = 10 +/- 3 mg and MB = 3 +/- 1 mL. TCD monitoring allowed direct visualization of massive MB arrival during every administration. In-procedure recanalization was observed in 78% (n= 7): complete-TICI3 in 22% (n= 2), partial-TICI2 in 56% (n= 5). Perfect correlation was observed between TICI and TCD scores. At 12 hours complete recanalization increased to 56%, partial to 22%. One patient (11%) experienced symptomatic intracranial hemorrhage accounting for the only death. Median NIHSS evolution was 12 at 24 hours and 10 at discharge. At 3 months 4 patients (44%) were independent. CONCLUSION: The combination of ultrasound and IA MB and tPA may be a strategy to enhance the thrombolytic effect and increase recanalization rates.
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