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(Stroke. 2006;37:1546.)
© 2006 American Heart Association, Inc.

Research Reports

Blood-Brain Barrier Disruption By Low-Frequency Ultrasound

Matthias Reinhard, MD; Andreas Hetzel, MD; Sebastian Krüger, MD; Stefan Kretzer, MD; Jochen Talazko, MD; Sargon Ziyeh, MD; Johannes Weber, MD Thomas Els, MD

From the Department of Neurology (M.R., A.H., S. Krüger, S. Kretzer, T.E.); the Department of Nuclear Medicine (J.T.); and the Department of Neuroradiology (S.Z., J.W.), University of Freiburg, Germany.

Correspondence to Andreas Hetzel, MD, Department of Neurology and Clinical Neurophysiology, University of Freiburg, Neurocenter, Breisacherstr. 64, D-79106 Freiburg, Germany. E-mail andreas.hetzel{at}uniklinik-freiburg.de

Background and Purpose— A recent study showed a dramatic increase in cerebral hemorrhage comprising atypical locations with low-frequency ultrasound–mediated recombinant tissue plasminogen activator–thrombolysis in humans. Here, we provide a possible explanation for this phenomenon by a side effect observed in a study using the similar ultrasound device.

Methods— The study was originally undertaken to investigate by transcranial Doppler sonography, positron emission tomography and perfusion MRI whether transcranial application of wide-field low-frequency ultrasound (300 kHz) improves cerebral hemodynamics in patients with cerebral small vessel disease.

Results— Showing no clear positive effect on cerebral hemodynamics in 4 patients and on cerebral perfusion (positron emission tomography) in 2 patients, the study has been terminated early because of a remarkable side effect in the first patient (a 62 year-old man) undergoing perfusion-MRI: detection of frontoparietal extravasation of Gadolinium contrast agent (applied during MRI perfusion imaging preinsonation) on MRI immediately postinsonation.

Conclusions— Abnormal permeability of the human blood-brain barrier can be induced by wide-field low-frequency insonation. The observed excessive bleeding rate with low-frequency sonothrombolysis might thus be attributable to primary blood-brain barrier disruption by ultrasound.

Key Words: blood-brain barrier • hemodynamic phenomena • leukoaraiosis • side effect • ultrasound

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