title: CLOTBUST-hands free: initial safety testing of a novel operator-independent ultrasound device in stroke-free volunteers.
abstract: OBJECTIVE
  We aimed to evaluate safety and tolerability of a novel operator-independent ultrasound device among stroke-free volunteers.
  
  
  METHODS
  A headframe containing 18 ultrasound transducers (each operating at 2 MHz, pulsed-wave) was used to expose both temporal windows and the suboccipital window. The transmission characteristics were set to emulate the acoustic characteristics of the exposure levels in the Combined Lysis of Thrombus in Brain Ischemia using Transcranial Ultrasound and Systemic tPA (CLOTBUST) trial and to never exceed Food and Drug Administration mandated diagnostic ultrasound exposure limits. Volunteers underwent 2 hours of insonation with transducer activation one at a time. Safety was captured using serial neurological examinations and pre- and postinsonation MRI for detection of the blood brain barrier permeability.
  
  
  RESULTS
  A total of 15 volunteers (40% men; 49 ± 16 years; 27% black; all pre-exposure National Institutes of Health Stroke Scale scores 0) were enrolled. Five volunteers received pulsed-wave ultrasound via the best pair temporal transducers, 5 via sequential activation of the suboccipital transducers, and 5 via sequential activation of all bilateral temporal and suboccipital transducers. All subjects were safely insonated with no adverse effects as indicated by the neurological examinations during, immediately after the exposure, and at 24 hours, and no abnormality of the blood brain barrier was found on any of the MRIs.
  
  
  CONCLUSIONS
  Our novel device was well tolerated by stroke-free volunteers and did not cause any neurological dysfunction nor did it affect blood brain barrier integrity. The safety and efficacy of the device are now being tested in stroke patients receiving intravenous tissue-type plasminogen activator in phase II-III clinical trials.
authors.affiliation: Department of Neurology, Comprehensive Stroke Center, The University of Alabama at Birmingham, RWUH M226, 619 19th St South, Birmingham, AL 35249-3280, USA.
authors.forename: Kristian
authors.initials: K
authors.lastname: Barlinn
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Barreto
authors.forename: April
authors.initials: A
authors.lastname: Sisson
authors.forename: David S
authors.initials: DS
authors.lastname: Liebeskind
authors.forename: Mark E
authors.initials: ME
authors.lastname: Schafer
authors.forename: John
authors.initials: J
authors.lastname: Alleman
authors.forename: Limin
authors.initials: L
authors.lastname: Zhao
authors.forename: Loren
authors.initials: L
authors.lastname: Shen
authors.forename: Luis F
authors.initials: LF
authors.lastname: Cava
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rahbar
authors.forename: James C
authors.initials: JC
authors.lastname: Grotta
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
mesh_terms: D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000473:pathology; D004869:Equipment Safety; D005260:Female; D006801:Humans; D020767:Intracranial Thrombosis / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D061185:Mechanical Thrombolysis / Q000295:instrumentation / Q000379:methods; D008875:Middle Aged; D020521:Stroke / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000295:instrumentation* / Q000379:methods; D014464:Ultrasonic Therapy / Q000295:instrumentation* / Q000379:methods
keywords: CLOTBUST; ischemic stroke; operator-independent device; reperfusion therapy