This Article Full Text Full Text (PDF) All Versions of this Article: 116/3/276    most recent CIRCULATIONAHA.106.684738v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kaufmann, B. A. Articles by Lindner, J. R. Search for Related Content PubMed PubMed Citation Articles by Kaufmann, B. A. Articles by Lindner, J. R. Related Collections Cardiovascular imaging agents/Techniques Imaging Related Article

(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.

---

 

CLINICAL PERSPECTIVE

Related Article:

Issue Highlights
Circulation 2007 116: 231. [Extract] [Full Text]

This article has been cited by other articles:

				J. R. Lindner Contrast ultrasound molecular imaging of inflammation in cardiovascular disease Cardiovasc Res, November 1, 2009; 84(2): 182 - 189. [Abstract] [Full Text] [PDF]

				M. Nahrendorf, E. Keliher, P. Panizzi, H. Zhang, S. Hembrador, J.-L. Figueiredo, E. Aikawa, K. Kelly, P. Libby, and R. Weissleder 18F-4V for PET-CT Imaging of VCAM-1 Expression in Atherosclerosis J. Am. Coll. Cardiol. Img., October 1, 2009; 2(10): 1213 - 1222. [Abstract] [Full Text] [PDF]

				B. A. Kaufmann Ultrasound molecular imaging of atherosclerosis Cardiovasc Res, September 1, 2009; 83(4): 617 - 625. [Abstract] [Full Text] [PDF]

				A. Saraste, S. G. Nekolla, and M. Schwaiger Cardiovascular molecular imaging: an overview Cardiovasc Res, September 1, 2009; 83(4): 643 - 652. [Abstract] [Full Text] [PDF]

				S. T. Laing and D. D. McPherson Cardiovascular therapeutic uses of targeted ultrasound contrast agents Cardiovasc Res, September 1, 2009; 83(4): 626 - 635. [Abstract] [Full Text] [PDF]

				O. Barreiro, R. J. Aguilar, E. Tejera, D. Megias, F. de Torres-Alba, A. Evangelista, and F. Sanchez-Madrid Specific Targeting of Human Inflamed Endothelium and In Situ Vascular Tissue Transfection by the Use of Ultrasound Contrast Agents J. Am. Coll. Cardiol. Img., August 1, 2009; 2(8): 997 - 1005. [Abstract] [Full Text] [PDF]

				J. R. Lindner and S. Chadderdon The Umbilical Cord: An Ally in Targeted Imaging Research? J. Am. Coll. Cardiol. Img., August 1, 2009; 2(8): 1006 - 1008. [Full Text] [PDF]

				R. P. Choudhury and E. A. Fisher Molecular Imaging in Atherosclerosis, Thrombosis, and Vascular Inflammation Arterioscler Thromb Vasc Biol, July 1, 2009; 29(7): 983 - 991. [Abstract] [Full Text] [PDF]

				K. G. Barringhaus and P. D. Zamore MicroRNAs: Regulating a Change of Heart Circulation, April 28, 2009; 119(16): 2217 - 2224. [Full Text] [PDF]

				A. J. Sinusas, F. Bengel, M. Nahrendorf, F. H. Epstein, J. C. Wu, F. S. Villanueva, Z. A. Fayad, and R. J. Gropler Multimodality Cardiovascular Molecular Imaging, Part I Circ Cardiovasc Imaging, November 1, 2008; 1(3): 244 - 256. [Full Text] [PDF]

				S. Kaul Myocardial Contrast Echocardiography: A 25-Year Retrospective Circulation, July 15, 2008; 118(3): 291 - 308. [Full Text] [PDF]

				C. Z. Behm, B. A. Kaufmann, C. Carr, M. Lankford, J. M. Sanders, C. E. Rose, S. Kaul, and J. R. Lindner Molecular Imaging of Endothelial Vascular Cell Adhesion Molecule-1 Expression and Inflammatory Cell Recruitment During Vasculogenesis and Ischemia-Mediated Arteriogenesis Circulation, June 3, 2008; 117(22): 2902 - 2911. [Abstract] [Full Text] [PDF]

				J. Sanz, P. R. Moreno, and V. Fuster The year in atherothrombosis. J. Am. Coll. Cardiol., March 4, 2008; 51(9): 944 - 955. [Full Text] [PDF]