Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics

Ultrasound Med Biol. 2016 May;42(5):1145-66. doi: 10.1016/j.ultrasmedbio.2015.12.011. Epub 2016 Jan 29.

Abstract

Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-μm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 μm, with no bubbles >44 μm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers.

Keywords: Acoustic cluster therapy; Droplet vaporization; Ex vivo bubble sizing; In vitro bubble sizing; In vivo bubble sizing; Microbubbles; Myocardial perfusion imaging; Ultrasound contrast agent.

MeSH terms

  • Animals
  • Blood Chemical Analysis*
  • Contrast Media / chemistry
  • Contrast Media / radiation effects
  • Delayed-Action Preparations
  • Dogs
  • Dose-Response Relationship, Radiation
  • Ferric Compounds / blood
  • Ferric Compounds / chemistry*
  • Ferric Compounds / radiation effects*
  • Gases / chemical synthesis
  • Gases / radiation effects
  • High-Energy Shock Waves
  • Iron / blood
  • Iron / chemistry*
  • Iron / radiation effects*
  • Male
  • Oxides / blood
  • Oxides / chemistry*
  • Oxides / radiation effects*
  • Particle Size
  • Radiation Dosage
  • Sonication / methods*

Substances

  • Contrast Media
  • Delayed-Action Preparations
  • Ferric Compounds
  • Gases
  • Oxides
  • Sonazoid
  • Iron