title: Improvements in cerebral blood flow and recanalization rates with transcranial diagnostic ultrasound and intravenous microbubbles after acute cerebral emboli.
abstract: OBJECTIVE
  Intravenous microbubbles (MBs) and transcutaneous ultrasound have been used to recanalize intra-arterial thrombi without the use of tissue plasminogen activator. In the setting of acute ischemic stroke, it was our objective to determine whether skull attenuation would limit the ability of ultrasound alone to induce the type and level of cavitation required to dissolve thrombi and improve cerebral blood flow (CBF) in acute ischemic stroke.
  
  
  METHODS
  In 40 pigs, bilateral internal carotid artery occlusions were created with 4-hour-old thrombi. Pigs were then randomized to high-mechanical index (MI = 2.4) short-pulse (5 microseconds) transcranial ultrasound (TUS) alone or a systemic MB infusion (3% Definity) with customized cavitation detection and imaging system transmitting either high-MI (2.4) short pulses (5 microseconds) or intermediate-MI (1.7) long pulses (20 microseconds). Angiographic recanalization rates of both internal carotids were compared in 24 of the pigs (8 per group), and quantitative analysis of CBF with perfusion magnetic resonance imaging was measured before, immediately after, and at 24 hours using T2* intensity versus time curves in 16 pigs.
  
  
  RESULTS
  Complete angiographic recanalization was achieved in 100% (8/8) of pigs treated with image-guided high-MI TUS and MBs, but in only 4 of 8 treated with high-MI TUS alone or 3 of 8 pigs treated with image-guided intermediate-MI TUS and MBs (both P < 0.05). Ipsilateral and contralateral CBF improved at 24 hours only after 2.4-MI 5-microsecond pulse treatments in the presence of MB (P < 0.005). There was no evidence of microvascular or macrovascular hemorrhage with any treatment.
  
  
  CONCLUSIONS
  Guided high-MI impulses from an ultrasound imaging system produce sustained improvements in ipsilateral and contralateral CBF after acute cerebral emboli.
authors.affiliation: From the *Department of Internal Medicine, Division of Cardiology, University of Nebraska Medical Center; †Department of Radiology, University of Nebraska Medical Center, Omaha, Nebraska; ‡Philips Research North America, Briarcliff Manor, NY; §Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska; ∥Philips Medical Systems, Bothell, WA; and ¶Department of Biostatistics, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Shunji
authors.initials: S
authors.lastname: Gao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Juefei
authors.initials: J
authors.lastname: Wu
authors.forename: William T
authors.initials: WT
authors.lastname: Shi
authors.forename: John
authors.initials: J
authors.lastname: Lof
authors.forename: Francois
authors.initials: F
authors.lastname: Vignon
authors.forename: Lucas
authors.initials: L
authors.lastname: Drvol
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.forename: David
authors.initials: D
authors.lastname: Muirhead
authors.forename: Jeffry E
authors.initials: JE
authors.lastname: Powers
authors.forename: Robin
authors.initials: R
authors.lastname: High
authors.forename: Matthew L
authors.initials: ML
authors.lastname: White
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Porter
mesh_terms: D000208:Acute Disease; D000818:Animals; D002560:Cerebrovascular Circulation; D005260:Female; D007275:Injections, Intravenous; D020766:Intracranial Embolism / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D045423:Microbubbles / Q000627:therapeutic use*; D013552:Swine; D014464:Ultrasonic Therapy / Q000379:methods; D017585:Ultrasonography, Doppler, Transcranial