Potential of Magnetic Resonance-guided Focused Ultrasound for Intracranial Hemorrhage: An In聽Vivo Feasibility Study

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• 作者：Sagi Harnof ; MD^&lowast ; ; ^{sagi.harnof@sheba.health.gov.il" class="auth_mail} ; Zion Zibly ; MD^&lowast ; ; Arik Hananel ; MD^&dagger ; ; Stephen Monteith ; MD^&Dagger ; ; Javier Grinfeld ; BSc^§ ; ; Gilat Schiff ; BSc^§ ; ; Iris Kulbatski ; PhD^&lowast ; ; Neal Kassell ; MD^&Dagger ;
• 关键词：Magnetic resonance-guided focused ultrasound ; intracranial hemorrhage ; thrombolysis ; noninvasive ; stroke ; real-time MR imaging ; trans-skull ; high-intensity focused ultrasound
• 刊名：Journal of Stroke and Cerebrovascular Diseases
• 出版年：July 2014
• 年：2014
• 卷：23
• 期：6
• 页码：1585-1591
• 全文大小：818 K

文摘

Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative noninvasive treatment through the precise delivery of FUS under real-time MR imaging (MRI) guidance. The purpose of the present study was to optimize the parameters for rapid, effective, and safe trans-skull large clot liquefaction using in vivo porcine and ex vivo human skull models to provide a clinically relevant proof of concept.

Methods

The transcranial effectiveness of MRgFUS was tested ex vivo by introducing a porcine blood clot into a human skull, without introducing tissue plasminogen activator (tPA). We used an experimental human head device to deliver pulsed FUS sonications at an acoustic power of 600-900 W for 5-10 seconds. A 3-mL clot was also introduced in a porcine brain and sonicated in vivo with one 5-second pulse of 700 W through a bone window or with 3000 W when treated through an ex vivo human skull. Treatment targeting was guided by MRI, and the tissue temperature was monitored online. Liquefied volumes were measured as hyperintense regions on T2-weighted MR images.

Results

In both in vivo porcine blood clot through a craniectomy model and the porcine clot in an ex vivo human skull model targeted clot liquefaction was achieved, with only marginal increase in temperature in the surrounding tissue.

Conclusions

Our results demonstrate the feasibility of fast, efficient, and safe thrombolysis in an in vivo porcine model of ICH and in 2 ex vivo models using a human skull, without introducing tPA. Future studies will further optimize parameters and assess the nature of sonication-mediated versus natural clot lysis, the risk of rebleeding, the potential effect on the adjacent parenchyma, and the chemical and toxicity profiles of resulting lysate particles.