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(Circulation. 2007;116:276-284.)
© 2007 American Heart Association, Inc.

Imaging

Molecular Imaging of Inflammation in Atherosclerosis With Targeted Ultrasound Detection of Vascular Cell Adhesion Molecule-1

Beat A. Kaufmann, MD; John M. Sanders, BS; Christopher Davis, MD; Aris Xie, MS; Patrick Aldred, MS; Ian J. Sarembock, MB, ChB; Jonathan R. Lindner, MD

From the Cardiovascular Divisions of Oregon Health and Sciences University, Portland (B.A.K., A.X., P.A., J.R.L.); and the University of Virginia, Charlottesville (J.M.S., C.D., I.J.S.).

Correspondence to Jonathan R. Lindner, MD, Cardiovascular Division, UHN62, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239. E-mail lindnerj{at}ohsu.edu

Received December 15, 2006; accepted May 7, 2007.

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.

Methods and 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.

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