title: Therapeutic application of 20-kHz transcranial ultrasound in an embolic middle cerebral artery occlusion model in rats: safety concerns.
abstract: OBJECTIVE
  Therapeutic application of diagnostic ultrasound has been shown to improve recanalization rates in patients with acute cerebral vessel occlusion. There is experimental evidence that low-frequency ultrasound may be superior. This study was designed to evaluate the therapeutic efficacy and safety of low-frequency ultrasound in an embolic middle cerebral artery occlusion model in rats. A parameter setting was used that had not previously shown any side effects and interactions with healthy rat brain tissue.
  
  
  METHODS
  Male Wistar rats were submitted to middle cerebral artery clot embolism and transcranial treatment with 20-kHz continuous-wave ultrasound (0.2 W/cm(2)), either alone or in combination with recombinant tissue-type plasminogen activator. Control groups received no treatment or recombinant tissue-type plasminogen activator alone. Outcome assessment consisted of determination of infarct volume and neurological evaluation.
  
  
  RESULTS
  Eleven animals treated with ultrasound died during the follow-up period of 7 days, compared with 2 animals in the control groups (P=0.028). In 3 animals, subarachnoid hemorrhage was detected (1 in the control group). The other animals that died displayed secondary worsening after an initial period of normal vigilance. Histological examination revealed massive edema formation. In surviving animals, no benefit of treatment could be demonstrated.
  
  
  CONCLUSIONS
  In this study, 20-kHz continuous-wave ultrasound caused death in a significant number of animals. Ultrasound at 20 kHz does not seem to be suitable for transcranial therapeutic cerebral application. The data underline the necessity to obtain further animal data to establish the safety limits of frequency and power output.
authors.affiliation: Department of Neurology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wilhelm-Schwenkmezger
authors.forename: Patrick
authors.initials: P
authors.lastname: Pittermann
authors.forename: Katharina
authors.initials: K
authors.lastname: Zajonz
authors.forename: Oliver
authors.initials: O
authors.lastname: Kempski
authors.forename: Marianne
authors.initials: M
authors.lastname: Dieterich
authors.forename: Max
authors.initials: M
authors.lastname: Nedelmann
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014464:Ultrasonic Therapy / Q000009:adverse effects* / Q000379:methods*