title: Blood-brain barrier disruption by low-frequency ultrasound.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, University of Freiburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Reinhard
authors.forename: Andreas
authors.initials: A
authors.lastname: Hetzel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Krüger
authors.forename: Stefan
authors.initials: S
authors.lastname: Kretzer
authors.forename: Jochen
authors.initials: J
authors.lastname: Talazko
authors.forename: Sargon
authors.initials: S
authors.lastname: Ziyeh
authors.forename: Johannes
authors.initials: J
authors.lastname: Weber
authors.forename: Thomas
authors.initials: T
authors.lastname: Els
mesh_terms: D000368:Aged; D001812:Blood-Brain Barrier / Q000528:radiation effects*; D002545:Brain Ischemia / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D002560:Cerebrovascular Circulation / Q000528:radiation effects; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000209:etiology; D005625:Frontal Lobe / Q000098:blood supply; D006439:Hemodynamics / Q000528:radiation effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000098:blood supply; D049268:Positron-Emission Tomography; D014464:Ultrasonic Therapy / Q000009:adverse effects*; D017585:Ultrasonography, Doppler, Transcranial