Intravascular ultrasound molecular imaging of atheroma components in vivo.
OBJECTIVE
Our purpose was to quantitate and confirm specific echogenic immunoliposome (ELIP) atheroma component enhancement in vivo.


BACKGROUND
Targeted ELIPs for ultrasonic detection and staging of active molecular components of endothelium and atheroma have been developed.


METHODS
In Yucatan miniswine, the endothelium was injured from one femoral and one carotid artery, and animals were fed a high-cholesterol diet for two months to create various stages of atheroma. Arteries were imaged with intravascular ultrasound (IVUS) 5 and 10 min after ELIP injection (5-mg dose). Anti-intercellular adhesion molecule-1 (ICAM-1), anti-vascular cell adhesion molecule-1 (VCAM-1), anti-fibrin, anti-fibrinogen, and anti-tissue factor (TF) conjugated ELIPs were used, and immunohistochemistry (IHC) confirmed the presence or absence of molecular expression. Two blinded observers determined if each segment was enhanced by ELIP. Three-dimensional image reconstruction and videodensitometric analysis determined the mean gray-scale (MGS) change of the luminal border.


RESULTS
To determine endothelial injury component enhancement, anti-fibrinogen ELIP enhanced exposed fibrin in all arteries (MGS increased 22 +/- 5%; 6 arteries; 2 animals). To determine enhancement of molecular components in atherosclerotic arteries, observers detected enhancement 5 min after anti-VCAM, anti-ICAM, anti-TF, anti-fibrin, and anti-fibrinogen conjugated ELIPs. Furthermore, ELIP enhanced atheroma MGS by 39 +/- 18% (n = 8). The IHC staining confirmed the expression of respective molecular targets in all enhanced segments.


CONCLUSIONS
It was shown that ELIPs specifically enhance endothelial injury/atheroma components. This allows better characterization of the type and extent of active atheroma components and may allow more directed therapy.
Hamilton
Andrew J
AJ
Department of Medicine, Division of Cardiology, Feinberg School of Medicine, Northwestern University, 251 East Huron, Galter 8-230 Chicago, IL 60611-2908, USA.
Huang
Shao-Ling
SL
Warnick
Drew
D
Rabbat
Mark
M
Kane
Bonnie
B
Nagaraj
Ashwin
A
Klegerman
Melvin
M
McPherson
David D
DD
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001161:Arteriosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D001798:Blood Proteins / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000378:metabolism; D019160:Endosonography / Q000379:methods*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000378:metabolism; D007150:Immunohistochemistry; D008081:Liposomes; D023421:Models, Animal; D013552:Swine
D000906:Antibodies; D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D008081:Liposomes