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.
Key Words
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Article info
Publication history
Published online: April 11, 2014
Accepted:
December 28,
2013
Received in revised form:
December 16,
2013
Received:
August 29,
2013
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.044
Copyright
© 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
