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

Laboratory investigation

Restricted access

Object

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.

Conclusions

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.

Article Information

Address correspondence to: Stephen J. Monteith, M.D., Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia 22908. email: stephen.monteith@gmail.com.

Please include this information when citing this paper: published online January 18, 2013; DOI: 10.3171/2012.12.JNS121095.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Transcranial MRgFUS in vitro parameter testing. Clotted blood in ultrasound transparent trays (A) was targeted with MRI guidance (B) with different combinations of power, sonication duration, and duty cycle. The lysis volume of increased T2 signal on MRI was measured (C). Maximal lysis (D) was achieved with the following parameters: frequency 230 kHz, power 3950 W, duty cycle 10%, and sonication duration 30 seconds. s = seconds.

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    Control group for ICH in swine. A: A T2-weighted MR image demonstrating surrounding edema and mass effect on the lateral ventricle. The clot initially exhibits mixed T2 signal as seen here. B: Gradient echo MR image revealing dark signal, comparable to that of human ICH. C: Formalin-fixed specimen showing a discrete, well-formed ICH. D: Similar to human ICH, H & E staining demonstrates surrounding edema without additional neuronal damage adjacent to the implanted ICH, making the model ideal for testing with MRgFUS.

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    Transcranial MRgFUS for ICH in swine. A: Image obtained pretreatment of an ICH showing a dark mixed T2 signal. B: Image acquired after MRgFUS treatment demonstrating complete sonothrombolysis with increased T2 signal. C: Image obtained for MRI-guided aspiration of a liquefied clot using an 18-gauge angiocatheter. D: Postaspiration image revealing minimal residual. E and F: Gross pathological and histological images demonstrating no edema or additional neuronal damage to the surrounding brain as a result of MRgFUS. H & E, original magnification ×2 (F).

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    MRgFUS sonothrombolysis parameters tested in normal swine frontal lobe following craniectomy. A: A transient temperature rise (6°C above baseline) measured by real-time MR thermometry confirms accurate energy delivery at target. B: Gross pathological specimens are normal without evidence of Evans blue leakage or BBB disruption. C and D: Low-power white matter and cortex photomicrographs showing no evidence of BBB disruption, edema, or neuronal injury at target or distant sites. H & E, original magnification ×10. Postprocedural MR imaging was unchanged from baseline without evidence of Gd contrast leakage (not shown).

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    Transcranial MRgFUS sonothrombolysis of IVH after the first sonication. A: The cadaver is shaved, placed in the stereotactic frame, and the transducer is filled with degassed water. B: The blue circle represents the treatment plan for the first sonication to be made in the middle of the IVH. The green circle represents the treatment envelope and can be expanded intraoperatively by moving the transducer. C–E: Sagittal, coronal, and axial T2-weighted MRI acquired after 1 sonication clearly demonstrating increased T2 signal caused by sonothrombolysis compared with respective images obtained before sonication (insets).

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    Transcranial MRgFUS lysis and aspiration of ICHs with T2-weighted MRI. A: Preoperative image demonstrating a solid dark T2-weighted ICH in the right basal ganglia. B: Following transcranial MRgFUS, greater than 95% of the ICH is liquefied. Note the development of fluid-fluid levels in the clot cavity not present in the Panel A images despite adequate clot retraction time, as well as the maintenance of a dark T2 signal of solid clot in the lateral ventricle (area not targeted). C: Image (T2 weighted) obtained after minimally invasive (< 1-cm incision) MRI-guided drainage, demonstrating minimal residual ICH with improved mass effect.

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