title: Influences of microbubble diameter and ultrasonic parameters on in vitro sonothrombolysis efficacy.
abstract: OBJECTIVE
  To quantify the effects of microbubble (MB) size, elasticity, and pulsed ultrasonic parameters on in vitro sonothrombolysis (ultrasound [US]-mediated thrombolysis) efficacy.
  
  
  METHODS
  Monodispersive MBs with diameters of 1 μm or 3 μm were exposed to pulsed US (1 MHz or 3 MHz) to lyse rabbit blood clots. Sonothrombolysis efficacy (clot mass loss) was measured as functions of MB size and concentration, ultrasonic frequency and intensity, pulse duration (PD), pulse repeat frequency (PRF), and duty factor.
  
  
  RESULTS
  Sonothrombolysis at 1 MHz was more effective using 3-μm MBs and at 3 MHz using 1-μm MBs. Sonothrombolysis was more effective at 1 MHz when≥75% of MBs remained intact, especially for 3-μm MBs; improving sonothrombolysis by increasing PRF from 100 Hz to 400 Hz at 3 MHz was associated with increasing 3-μm MB survival. However, 60% of 1-μm MBs were destroyed during maximal sonothrombolysis at 3 MHz, indicating that considerable MB collapse may be required for sonothrombolysis under these conditions.
  
  
  CONCLUSIONS
  The ability to control MB size and elasticity permits using a wide range of US parameters (eg, frequency, intensity) to produce desired levels of sonothrombolysis. Comparable, maximal sonothrombolysis efficacy was achieved at 20-fold lower intensity with 3-μm MBs (0.1W/cm(2)) than with 1-μm MBs (2.0W/cm(2)), a potential safety issue for in vivo sonothrombolysis. US parameters that maximized MB survival yielded maximal sonothrombolysis efficacy except with 1-μm MBs at 3MHz where most MBs were destroyed.
authors.affiliation: Department of Radiology, University of Arkansas for Medical Sciences, 4301 West Markham Street Slot #556, Little Rock, AR 72205, USA. mjborrelli@uams.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borrelli
authors.forename: William D
authors.initials: WD
authors.lastname: O'Brien
authors.forename: Eric
authors.initials: E
authors.lastname: Hamilton
authors.forename: Michael L
authors.initials: ML
authors.lastname: Oelze
authors.forename: Jonah
authors.initials: J
authors.lastname: Wu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bernock
authors.forename: Stephen
authors.initials: S
authors.lastname: Tung
authors.forename: Husein
authors.initials: H
authors.lastname: Rokadia
authors.forename: William C
authors.initials: WC
authors.lastname: Culp
mesh_terms: D000818:Animals; D001769:Blood; D001777:Blood Coagulation / Q000502:physiology* / Q000528:radiation effects*; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D061185:Mechanical Thrombolysis / Q000379:methods*; D045423:Microbubbles / Q000627:therapeutic use*; D010316:Particle Size; D011817:Rabbits; D011829:Radiation Dosage; D016896:Treatment Outcome