Acoustic radiation force enhances ultrasound contrast agent retention to P-selectin in vivo

Joshua J. Rychak, Klaus Ley, Alexander Klibanov, John Hossack

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

Recent studies have shown that targeted ultrasound contrast agents known as microbubbles (MB) can achieve specific adhesion to intravascular pathology. This may enable noninvasive diagnosis of disease at the molecular level using contrast-enhanced ultrasound (CEU). However, several investigations have suggested that the ability of injected contrast agents to contact the blood vessel surface, where the molecular markers of disease are located, may to be weak, especially in large or high-flow vessels. This deficiency may limit the usefulness of targeted CEU using these agents. It has been hypothesized that the efficacy of this technique may be improved by increasing the number of circulating MB that contact and adhere to the intended endothelial target site. Low-intensity acoustic radiation has been used to cause the directional migration of targeted MB toward the vessel wall in several in vitro systems. In the current study we present evidence that this technique enhances adhesion of MB targeted to the pro-inflammatory endothelial protein P-selectin in vivo. We assessed the retention of MB bearing the antiP-selectin antibody Rb40.34 in mouse models of inflammation of the cremaster microcirculation and the femoral vessels. Low-intensity acoustic force was applied for several minutes immediately after MB injection, and MB retention was assessed using intravital microscopy in 10-20 microscopic fields of view. Targeted MB exhibited a 5-fold greater retention following application of acoustic radiation in the cremaster microcirculation, a 2.5-fold increase in the femoral vein, and a 20-fold increase in the femoral artery. These results suggest that low-intensity radiation force is a viable mechanism for enhancing MB retention for imaging inflammation.

Original languageEnglish (US)
Title of host publication2005 IEEE Ultrasonics Symposium
Pages1703-1707
Number of pages5
DOIs
StatePublished - 2005
Externally publishedYes
Event2005 IEEE Ultrasonics Symposium - Rotterdam, Netherlands
Duration: Sep 18 2005Sep 21 2005

Publication series

NameProceedings - IEEE Ultrasonics Symposium
Volume3
ISSN (Print)1051-0117

Conference

Conference2005 IEEE Ultrasonics Symposium
Country/TerritoryNetherlands
CityRotterdam
Period9/18/059/21/05

Keywords

  • Acoustic radiation force
  • Inflammation
  • Microbubble
  • P-selectin
  • Ultrasound contrast

ASJC Scopus subject areas

  • Acoustics and Ultrasonics

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