Published Online
on April 27, 2006

A more recent version of this article appeared on June 1, 2006

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Submitted on October 22, 2005
Revised on February 27, 2006
Accepted on February 28, 2006

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; and 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.

^* To whom correspondence should be addressed. 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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