Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube.
Methods and Results
In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance.
The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.
Abbreviations used in this paper:BBB = blood-brain barrier; ICH = intracerebral hemorrhage; ICP = intracranial pressure; IVH = intraventricular hemorrhage; MRgFUS = MR-guided focused ultrasound; tPA = tissue plasminogen activator.
HynynenKClementGTMcDannoldNVykhodtsevaNKingRWhitePJ: 500-element ultrasound phased array system for noninvasive focal surgery of the brain: a preliminary rabbit study with ex vivo human skulls. Magn Reson Med52:100–1072004
HynynenKMcDannoldNClementGJoleszFAZadicarioEKillianyR: Pre-clinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain—a primate study. Eur J Radiol59:149–1562006
MendelowADGregsonBAFernandesHMMurrayGDTeasdaleGMHopeDT: Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet365:387–3972005
MonteithSJHarnofSKassellNFMoldovanKWintermarkMEamesM: Transcranial MRI guided focused ultrasound sonothrombolysis for intracerebral hemorrhage: a feasibility study using a phantom skull. Presented at the Congress of Neurological Surgeons Annual MeetingWashington DC2011. (Abstract) (http://w3.cns.org/dp/2011CNS/1058.pdf) [Accessed December 7 2012]
MonteithSJHarnofSKassellNFWintermarkMZadicarioEFoleyJ: Transcranial MR guided focused ultrasound treatment of intracerebral haemorrhage (ICH). Presented at the World ICH ConferenceNewcastle Upon Tyne, England2011. (Abstract) (http://jns-jps.ejpress.com/cgi-bin/prod.plex?jps_action=query_detail_display&c_id=3723&c_key=BdaTYs70PXt9RTZ0plkw&j_id=99&new_window=1&query_id=12220&query_type_cde=9) [Accessed December 10 2012]
MorganTZuccarelloMNarayanRKeylPLaneKHanleyD: Preliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial. Acta Neurochir Suppl105:147–1512008
RohdeVRohdeIThiexRInceAJungADückersG: Fibrinolysis therapy achieved with tissue plasminogen activator and aspiration of the liquefied clot after experimental intracerebral hemorrhage: rapid reduction in hematoma volume but intensification of delayed edema formation. J Neurosurg97:954–9622002
WagnerKRXiGHuaYZuccarelloMde Courten-MyersGMBroderickJP: Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage: edema reduction and blood-brain barrier protection. J Neurosurg90:491–4981999