title: Rest-Stress Limb Perfusion Imaging in Humans with Contrast Ultrasound Using Intermediate-Power Imaging and Microbubbles Resistant to Inertial Cavitation.
abstract: BACKGROUND
  Contrast-enhanced ultrasound (CEU) limb perfusion imaging is a promising approach for evaluating peripheral artery disease (PAD). However, low signal enhancement in skeletal muscle has necessitated high-power intermittent imaging algorithms, which are not clinically feasible. We hypothesized that CEU using a combination of intermediate power and a contrast agent resistant to inertial cavitation would allow real-time limb stress perfusion imaging.
  
  
  METHODS
  In normal volunteers, CEU of the calf skeletal muscle was performed on separate days with Sonazoid, Optison, or Definity. Progressive reduction in the ultrasound pulsing interval was used to assess the balance between signal enhancement and agent destruction at escalating mechanical indices (MI, 0.1-0.4). Real-time perfusion imaging at MI 0.1-0.4 using postdestructive replenishment kinetics was performed at rest and during 25 W plantar flexion contractile exercise.
  
  
  RESULTS
  For Optison, limb perfusion imaging was unreliable at rest due to very low signal enhancement generated at all MIs and was possible during exercise-induced hyperemia only at MI 0.1 due to agent destruction at higher MIs. For Definity, signal intensity progressively increased with MI but was offset by microbubble destruction, which resulted in modest signal enhancement during CEU perfusion imaging and distortion of replenishment curves at MI ≥ 0.2. For Sonazoid, there strong signal enhancement at MI ≥ 0.2, with little destruction detected only at MI 0.4. Accordingly, high signal intensity and nondistorted perfusion imaging was possible at MI 0.2-0.3 and detected an 8.0- ± 5.7-fold flow reserve.
  
  
  CONCLUSIONS
  Rest-stress limb perfusion imaging in humans with real-time CEU, which requires only seconds to perform, is possible using microbubbles with viscoelastic properties that produce strong nonlinear signal generation without destruction at intermediate acoustic pressures.
authors.affiliation: Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon; Portland VA Medical Center, Portland, Oregon.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Davidson
authors.affiliation: Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon.
authors.forename: James
authors.initials: J
authors.lastname: Hodovan
authors.affiliation: Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon.
authors.forename: J Todd
authors.initials: JT
authors.lastname: Belcik
authors.affiliation: Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon.
authors.forename: Federico
authors.initials: F
authors.lastname: Moccetti
authors.affiliation: Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon.
authors.forename: Aris
authors.initials: A
authors.lastname: Xie
authors.affiliation: Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon.
authors.forename: Azzdine Y
authors.initials: AY
authors.lastname: Ammi
authors.affiliation: Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon; Oregon National Primate Research Center, Oregon Health and Science University, Portland, Oregon. Electronic address: lindnerj@ohsu.edu.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lindner
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000502:physiology*; D003287:Contrast Media; D005080:Exercise Test / Q000379:methods*; D005260:Female; D005466:Fluorocarbons; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007866:Leg / Q000098:blood supply / Q000502:physiology*; D008297:Male; D045423:Microbubbles; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology*; D055420:Perfusion Imaging / Q000379:methods*; D015203:Reproducibility of Results; D012146:Rest; D012680:Sensitivity and Specificity; D014463:Ultrasonography / Q000379:methods*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; C042852:perflutren
keywords: Contrast-enhanced ultrasound; Microbubbles; Peripheral artery disease