Sagi Harnof1, Zion Zibly2, Arik Hananel3, Stephen Monteith4, Javier Grinfeld5, Gilat Schiff5, Iris Kulbatski2, Neal Kassell4. 1. Department of Neurosurgery, Sheba Medical Center, Tel-Hashomer, Israel. Electronic address: sagi.harnof@sheba.health.gov.il. 2. Department of Neurosurgery, Sheba Medical Center, Tel-Hashomer, Israel. 3. FUS Foundation, Charlottesville, Virginia. 4. Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington. 5. InSightec Ltd, Tirat Carmel, Israel.
Abstract
BACKGROUND: 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.
BACKGROUND: 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.
Authors: Francesco Prada; M Yashar S Kalani; Kaan Yagmurlu; Pedro Norat; Massimiliano Del Bene; Francesco DiMeco; Neal F Kassell Journal: Neurotherapeutics Date: 2019-01 Impact factor: 7.620
Authors: Pejman Ghanouni; Kim Butts Pauly; W Jeff Elias; Jaimie Henderson; Jason Sheehan; Stephen Monteith; Max Wintermark Journal: AJR Am J Roentgenol Date: 2015-07 Impact factor: 3.959
Authors: Hongchae Baek; Daniel Lockwood; Emily Jo Mason; Emmanuel Obusez; Matthew Poturalski; Richard Rammo; Sean J Nagel; Stephen E Jones Journal: Front Neurol Date: 2022-05-09 Impact factor: 4.086
Authors: Marc Melià-Sorolla; Carlos Castaño; Núria DeGregorio-Rocasolano; Luis Rodríguez-Esparragoza; Antoni Dávalos; Octavi Martí-Sistac; Teresa Gasull Journal: Int J Mol Sci Date: 2020-09-08 Impact factor: 5.923