Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1

Beat A. Kaufmann, John M. Sanders, Christopher Davis, Aris Xie, Patrick Aldred, Ian J. Sarembock, Jonathan Lindner

    Research output: Contribution to journalArticle

    297 Citations (Scopus)

    Abstract

    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/cm). 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/cm) 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

    Original languageEnglish (US)
    Pages (from-to)276-284
    Number of pages9
    JournalCirculation
    Volume116
    Issue number3
    DOIs
    StatePublished - Jul 2007

    Fingerprint

    Microbubbles
    Molecular Imaging
    Vascular Cell Adhesion Molecule-1
    Atherosclerosis
    Inflammation
    Diet
    Apolipoproteins E
    Thoracic Aorta
    Intravenous Injections
    Cultured Cells
    Endothelial Cells
    Pulsatile Flow
    Blood Vessels
    Early Diagnosis
    Microscopy
    Ultrasonography
    Therapeutics

    Keywords

    • Atherosclerosis
    • Echocardiography
    • Imaging
    • Inflammation

    ASJC Scopus subject areas

    • Physiology
    • Cardiology and Cardiovascular Medicine

    Cite this

    Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1. / Kaufmann, Beat A.; Sanders, John M.; Davis, Christopher; Xie, Aris; Aldred, Patrick; Sarembock, Ian J.; Lindner, Jonathan.

    In: Circulation, Vol. 116, No. 3, 07.2007, p. 276-284.

    Research output: Contribution to journalArticle

    Kaufmann, Beat A. ; Sanders, John M. ; Davis, Christopher ; Xie, Aris ; Aldred, Patrick ; Sarembock, Ian J. ; Lindner, Jonathan. / Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1. In: Circulation. 2007 ; Vol. 116, No. 3. pp. 276-284.
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    AU - Kaufmann, Beat A.

    AU - Sanders, John M.

    AU - Davis, Christopher

    AU - Xie, Aris

    AU - Aldred, Patrick

    AU - Sarembock, Ian J.

    AU - Lindner, Jonathan

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    AB - 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/cm). 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/cm) 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

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