Abstract 9845: Efficacy and Safety of Transcranial Ultrasound and Microbubbles in Treating Acute Ischemic Stroke Without Thrombolytic Agents

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Background. Although transcranial ultrasound (TCUS) and microbubbles (MB) have been utilized in the emergent management of stroke, it remains unclear what TCUS parameters are required to be effective. Furthermore, it is unclear whether TCUS alone, without supplemental thrombolytic agents, could produce thrombolysis without intracranial hemmorhage (ICH). The purpose of this study was to determine whether TCUS pulse sequences which elicit predominately inertial cavitation (IC) versus stable cavitation (SC) of MB would be more effective in recanalizing the cerebral vessels in acute stroke. Methods. In 24 pigs, three hour old venous thrombi were embolized into the internal carotid and middle cerebral arteries. After angiographic documentation of persistent bilateral occlusion, pigs were randomized to a continuous infusion of MB using intravenous 3% Definity, during which either guided high mechanical index (MI) impulses (2.3 MI; 5 usec pulse duration) or guided intermediate MI impulses (1.7 MI, 20 usec pulse duration) were administered. The impulses were applied only when simultaneous low MI imaging detected MB within the cortex. A third control group received high MI impulses (2.3 MI) alone without MB. All pigs received aspirin. Radiofrequency (RF) data was collected from returning signals in all pigs to determine whether noise based IC or ultraharmonic based SC were created. Microscopic analysis (Hematoxylin/Eosin) was performed to analyze for ICH post-mortem. Results. Attenuation across the pig skull (measured ex vivo) using a calibrated hydrophone was >52% in all pigs. Recanalization rates were highest for guided high MI impulses in the presence of MB (8/8 versus 3/8 for guided intermediate MI impulses/MB and 4/8 for high MI TCUS alone; p<0.05). Although the intermediate MI impulses created both SC and IC, a more homogenous IC field was created with guided high MI impulses in the presence of MB. Microscopic analysis of ipsilateral and contralateral cortex indicated no ICH in any pig. Conclusions. TCUS and intravenous commercially available MB are capable of safely restoring cerebral blood flow without the need for thrombolytic agents. Achieving a dominant IC field appears critical to produce thrombolysis.