Pitt Shield

Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound.

Authors: Monteith SJ, Harnof S, Medel R, Popp B, Wintermark M, Lopes MB, Kassell NF, Elias WJ, Snell J, Eames M, Zadicario E, Moldovan K, Sheehan J

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. 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.

Introduction

Purpose sonobiopsy
Study Objective To assess the feasibility and safety of transcranial MRgFUS for liquefying intracerebral hemorrhage to enable minimally invasive evacuation.
Animal model / Human subject swine 20kg
Disease model Intracerebral hemorrhage (ICH)
MRI or image guidance method Yes (MRI)
Targeted brain region(s) Frontal Lobe, Basal Ganglia

Outcomes and Safety

Summary of Outcomes Transcranial MRgFUS effectively liquefied ICH clots in vitro, in a swine model, and in cadaveric brains, enabling minimally invasive aspiration without causing additional brain injury, BBB disruption, or thermal damage.

Brain Region

Ultrasound Parameters

Ultrasound instrument ExAblate Neuro, InSightec
FUS Frequency 230kHz
FUS Mode pulsed
Pulse duration 100 μs
Duration of a single FUS session 30s
Treatment frequency single session

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