title: Potential of magnetic resonance-guided focused ultrasound for intracranial hemorrhage: an in vivo feasibility study.
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.
authors.affiliation: Department of Neurosurgery, Sheba Medical Center, Tel-Hashomer, Israel. Electronic address: sagi.harnof@sheba.health.gov.il.
authors.forename: Sagi
authors.initials: S
authors.lastname: Harnof
authors.affiliation: Department of Neurosurgery, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Zion
authors.initials: Z
authors.lastname: Zibly
authors.affiliation: FUS Foundation, Charlottesville, Virginia.
authors.forename: Arik
authors.initials: A
authors.lastname: Hananel
authors.affiliation: Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington.
authors.forename: Stephen
authors.initials: S
authors.lastname: Monteith
authors.affiliation: InSightec Ltd, Tirat Carmel, Israel.
authors.forename: Javier
authors.initials: J
authors.lastname: Grinfeld
authors.affiliation: InSightec Ltd, Tirat Carmel, Israel.
authors.forename: Gilat
authors.initials: G
authors.lastname: Schiff
authors.affiliation: Department of Neurosurgery, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Kulbatski
authors.affiliation: Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington.
authors.forename: Neal
authors.initials: N
authors.lastname: Kassell
mesh_terms: D000818:Animals; D005240:Feasibility Studies; D006801:Humans; D020300:Intracranial Hemorrhages / Q000628:therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008953:Models, Anatomic; D013552:Swine; D014464:Ultrasonic Therapy / Q000295:instrumentation*
keywords: Magnetic resonance-guided focused ultrasound; high-intensity focused ultrasound; intracranial hemorrhage; noninvasive; real-time MR imaging; stroke; thrombolysis; trans-skull