Enhanced targeting of ultrasound contrast agents using acoustic radiation force.
Contrast-enhanced ultrasound has shown significant promise as a molecular imaging modality. However, one potential drawback is the difficulty that ultrasound contrast agents (UCA) may have in achieving adhesion to target molecules on the vascular endothelium. Microbubble UCA exhibit a lateral migration toward the vessel axis in laminar flow, preventing UCA contact with the endothelium. In the current study, we have investigated low-amplitude acoustic radiation as a mechanism to move circulating UCA toward targeted endothelium. Intravital microscopy was used to assess the retention of microbubble UCA targeted to P-selectin in the mouse cremaster microcirculation and femoral vessels. Acoustic treatment enhanced UCA retention to P-selectin four-fold in cremaster venules and in the femoral vein and 20-fold in the femoral artery. These results suggest acoustic treatment as a mechanism for enabling ultrasound-based molecular imaging in blood vessels with hemodynamic and anatomical conditions otherwise adversarial for UCA retention.
Rychak
Joshua J
JJ
University of Virginia Cardiovascular Research Center, Charlottesville, VA 22908, USA.
Klibanov
Alexander L
AL
Ley
Klaus F
KF
Hossack
John A
JA
D000009:Abdominal Muscles / Q000098:blood supply; D000818:Animals; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000737:chemistry; D005263:Femoral Artery / Q000737:chemistry; D005268:Femoral Vein / Q000737:chemistry; D005466:Fluorocarbons; D007962:Leukocytes / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D045423:Microbubbles; D008833:Microcirculation; D023421:Models, Animal; D019007:P-Selectin; D010316:Particle Size; D014465:Ultrasonics; D014463:Ultrasonography / Q000379:methods
D005466:Fluorocarbons; D019007:P-Selectin; C108042:perfluorobutane