Use of intravital microscopy to study the microvascular behavior of microbubble-based ultrasound contrast agents.
OBJECTIVE
The study describes the use of intravital microscopy (IVM) to assess the behavior of ultrasound contrast agents (UCAs), including targeted UCAs, in the microcirculation of rodents.


METHODS
IVM was performed on various exteriorized organs: hamster cheek pouch, rat mesentery, liver, spinotrapezius muscle, and mouse cremaster muscle. A dorsal skin-fold chamber with MatBIII tumor cells was also implanted in rats. Nontargeted UCAs (SonoVue(®) and BR14) and targeted UCAs (BR55 and P-selectin targeted microbubbles) were tested. IVM was used to measure microbubble size, determine their persistence, and observe their behavior in the blood circulation.


RESULTS
Intravenous and intra-arterial injections of high doses of UCAs did not modify the local microvascular hemodynamics. No microbubble coalescence and no increased size were observed. Adhesion of some microbubbles to leukocytes was observed in various microcirculation models. Microbubbles are captured by Kupffer cells in the liver. Targeted microbubbles were shown to adhere specifically to endothelial receptors without compromising local blood flow.


CONCLUSIONS
These results support the safety of both targeted and nontargeted UCAs as no microvascular flow alteration or plugging of microvessels were observed. They confirm that binding observed with targeted microbubbles are due to the binding of these microbubbles to specific endothelial receptors.
Bracco Suisse SA, Plan-les-Ouates, Switzerland.
Michel
M
Schneider
Anne
A
Broillet
Isabelle
I
Tardy
Sibylle
S
Pochon
Philippe
P
Bussat
Thierry
T
Bettinger
Alexandre
A
Helbert
Maria
M
Costa
François
F
Tranquart
D000818:Animals; D002610:Cheek / Q000098:blood supply; D003287:Contrast Media / Q000008:administration & dosage; D006224:Cricetinae; D005466:Fluorocarbons / Q000008:administration & dosage; D007269:Injections, Intra-Arterial; D008102:Liver Circulation; D051379:Mice; D045423:Microbubbles; D018715:Microscopy, Video / Q000379:methods*; D055806:Microvessels / Q000000981:diagnostic imaging* / Q000502:physiology; D023421:Models, Animal; D009132:Muscles / Q000098:blood supply; D009374:Neoplasms, Experimental / Q000098:blood supply; D010743:Phospholipids / Q000008:administration & dosage; D051381:Rats; D013152:Splanchnic Circulation; D013459:Sulfur Hexafluoride / Q000008:administration & dosage; D014463:Ultrasonography
C471302:BR14 contrast agent; D003287:Contrast Media; D005466:Fluorocarbons; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride