Intra-arterial Administration of Microbubbles and Continuous 2-MHz Ultrasound Insonation to Enhance Intra-arterial Thrombolysis

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 < 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.