Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1.
BACKGROUND
The ability to image vascular inflammatory responses may allow early diagnosis and treatment of atherosclerosis. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) expression with contrast-enhanced ultrasound (CEU) could be used for this purpose.


RESULTS
Attachment of VCAM-1-targeted and control microbubbles to cultured endothelial cells was assessed in a flow chamber at variable shear stress (0.5 to 12.0 dynes/cm2). Microbubble attachment to aortic plaque was determined by en face microscopy of the thoracic aorta 10 minutes after intravenous injection in wild-type or apolipoprotein E-deficient mice on either chow or hypercholesterolemic diet. CEU molecular imaging of the thoracic aorta 10 minutes after intravenous microbubble injection was performed for the same animal groups. VCAM-1-targeted but not control microbubbles attached to cultured endothelial cells, although firm attachment at the highest shear rates (8 to 12 dynes/cm2) occurred only in pulsatile flow conditions. Aortic attachment of microbubbles and targeted CEU signal was very low in control wild-type mice on chow diet. Aortic attachment of microbubbles and CEU signal for VCAM-1-targeted microbubbles differed between treatment groups according to extent of VCAM-1-positive plaque formation (median CEU videointensity, 1.8 [95% CI, 1.2 to 1.7], 3.7 [95% CI, 2.9 to 7.3], 6.8 [95% CI, 3.9 to 7.6], and 11.2 [95% CI, 8.5 to 16.0] for wild-type mice on chow and hypercholesterolemic diet and for apolipoprotein E-deficient mice on chow and hypercholesterolemic diet, respectively; P<0.001).


CONCLUSIONS
CEU molecular imaging of VCAM-1 is capable of rapidly quantifying vascular inflammatory changes that occur in different stages of atherosclerosis. This method may be potentially useful for early risk stratification according to inflammatory phenotype.
Kaufmann
Beat A
BA
Cardiovascular Division, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
Sanders
John M
JM
Davis
Christopher
C
Xie
Aris
A
Aldred
Patrick
P
Sarembock
Ian J
IJ
Lindner
Jonathan R
JR
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D006937:Hypercholesterolemia / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism; D018836:Inflammation Mediators / Q000032:analysis* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D045423:Microbubbles; D014463:Ultrasonography / Q000379:methods*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis* / Q000096:biosynthesis
D001057:Apolipoproteins E; D018836:Inflammation Mediators; D019010:Vascular Cell Adhesion Molecule-1