Abstract
Atherosclerosis is an inflammatory disease of the arteries, which causes more than 19 million deaths worldwide every year. Most complications of atherosclerosis are caused by rupture of a vulnerable plaque. Currently, there are no imaging techniques available in clinical practice that can accurately identify a vulnerable plaque. There is an emerging role for Ultrasmall Super-paramagnetic Iron Oxide Particles (USPIOs) in MR imaging of atherosclerosis. This review will first give an update on the biology of atherosclerosis. Next, we will focus on the physicochemical properties of USPIOs and describe animal and human studies that showed USPIO uptake mainly in macrophages of atherosclerotic plaque, which could be detected as areas of focal signal loss in MR images. Novel superparamagnetic particles are currently being developed which enable visualization of other cell types and functions than macrophage uptake that are relevant for atherosclerosis. We conclude that USPIOs are a highly promising imaging tool for atherosclerosis and larger prospective studies are warranted to prove the value in daily clinical practice.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Anzai, Y., Piccoli, C.W., Outwater, E.K., et al., 2003. Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: phase III safety and efficacy study. Radiology 228, 777–788.
Bjornerud, A., Johansson, L., 2004. The utility of superparamagnetic contrast agents in MRI: theoretical consideration and applications in the cardiovascular system. NMR Biomed 17, 465–477.
Briley-Saebo, K.C., Mani, V., Hyafil, F., et al., 2006. Positive contrast MR imaging of in vivo atherosclerosis in a rabbit model using ultrasmall iron oxide particles. Proc. Intl. Soc. Mag. Reson. Med. 14, 563.
Buffon, A., Biasucci, L.M., Liuzzo, G., et al., 2002. Widespread coronary inflammation in unstable angina. N Engl J Med 347, 5–12.
Corot, C., Petry, K.G., Trivedi, R., et al., 2004. Macrophage imaging in central nervous system and in carotid atherosclerotic plaque using ultrasmall superparamagnetic iron oxide in magnetic resonance imaging. Invest Radiol 39, 619–625.
Cunningham, C.H., Arai, T., Yang, P.C., et al., 2005. Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magn Reson Med 53, 999–1005.
Dahnke, H., Liu, W., Frank, J., et al., 2006. Optimal positive contrast of labeled cells via conventional 3D imaging. Proc. Intl. Soc. Mag. Reson. Med. 14, 361.
Falk, E., Shah, P.K., Fuster, V., 1995. Coronary plaque disruption. Circulation 92, 657–71.
Gupta, A.K., Gupta, M., 2005. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26, 3995–4021.
Hansson, G.K., Libby, P., Schonbeck, U., et al., 2002. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 91, 281–291.
Hansson, G.K., 2005. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352, 1685–1695.
Hyafil, F., Laissy, J.P., Mazighi, M., et al., 2006. Ferumoxtran-10-enhanced MRI of the hypercholesterolemic rabbit aorta: relationship between signal loss and macrophage infiltration. Arterioscler Thromb Vasc Biol 26, 176–181.
Jung, C.W., Jacobs, P., 1995. Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn Reson Imaging 13, 661–674.
Kang, H.W., Torres, D., Wald, L., et al., 2006. Targeted imaging of human endothelial-specific marker in a model of adoptive cell transfer. Lab Invest 86, 599–609.
Kelly, K.A., Allport, J.R., Tsourkas, A., et al., 2005. Detection of vascular adhesion molecule-1 expression using a novel multimodal nanoparticle. Circ Res 96, 327–336.
Kooi, M.E., Cappendijk, V.C., Cleutjens, K.B., et al., 2003. Accumulation of Ultrasmall Superparamagnetic Particles of Iron Oxide in Human Atherosclerotic Plaques Can Be Detected by In Vivo Magnetic Resonance Imaging. Circulation 107, 2453–2458.
Leiner, T., Gerretsen, S., Botnar, R., et al., 2005. Magnetic resonance imaging of atherosclerosis. Eur Radiol 15, 1087–1099.
Litovsky, S., Madjid, M., Zarrabi, A., et al., 2003. Superparamagnetic iron oxide-based method for quantifying recruitment of monocytes to mouse atherosclerotic lesions in vivo: enhancement by tissue necrosis factor-alpha, interleukin-1beta, and interferon-gamma. Circulation 107, 1545–1549.
Madjid, M., Zarrabi, A., Litovsky, S., et al., 2004. Finding vulnerable atherosclerotic plaques: is it worth the effort? Arterioscler Thromb Vasc Biol 24, 1775–1782.
Mani, V., Briley-Saebo, K.C., Itskovich, V.V., et al., 2006. Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP): sequence characterization in membrane and glass superparamagnetic iron oxide phantoms at 1.5T and 3T. Magn Reson Med 55, 126–135.
Mauriello, A., Sangiorgi, G., Fratoni, S., et al., 2005. Diffuse and active inflammation occurs in both vulnerable and stable plaques of the entire coronary tree: a 5. Emerging Role of USPIOs for Imaging of Atherosclerosis 89 histopathologic study of patients dying of acute myocardial infarction. J Am Coll Cardiol 45, 1585–1593.
Metz, S., Bonaterra, G., Rudelius, M., et al., 2004. Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro. Eur Radiol 14, 1851–1858.
Naghavi, M., Libby, P., Falk, E., et al., 2003. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 108, 1664–1672.
Pande, A.N., Kohler, R.H., Aikawa, E., et al., 2006. Detection of macrophage activity in atherosclerosis in vivo using multichannel, high-resolution laser scanning fluorescence microscopy. J Biomed Opt 11, 21009.
Raynal, I., Prigent, P., Peyramaure, S., et al., 2004. Macrophage endocytosis of super-paramagnetic iron oxide nanoparticles: mechanisms and comparison of ferumoxides and ferumoxtran-10. Invest Radiol 39, 56–63.
Reimer, P., Rummeny, E.J., Daldrup, H.E., et al., 1995. Clinical results with Resovist: a phase 2 clinical trial. Radiology 195, 489–496.
Reimer, P., Tombach, B., 1998. Hepatic MRI with SPIO: detection and characterization of focal liver lesions. Eur Radiol 8, 1198–1204.
Rogers, W.J., Basu, P., 2005. Factors regulating macrophage endocytosis of nanoparticles: implications for targeted magnetic resonance plaque imaging. Atherosclerosis 178, 67–73.
Ruehm, S.G., Corot, C., Vogt, P., et al., 2001. Magnetic Resonance Imaging of Atherosclerotic Plaque With Ultrasmall Superparamagnetic Particles of Iron Oxide in Hyperlipidemic Rabbits. Circulation 103, 415–422.
Schmitz, S.A., Coupland, S.E., Gust, R., et al., 2000. Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits. Invest Radiol 35, 460–471.
Schmitz, S.A., Taupitz, M., Wagner, S., et al., 2001. Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles. J Magn Reson Imaging 14, 355–361.
Schmitz, S.A., Taupitz, M., Wagner, S., et al., 2002. Iron-oxide-enhanced magnetic resonance imaging of atherosclerotic plaques: postmortem analysis of accuracy, inter-observer agreement, and pitfalls. Invest Radiol 37, 405–411.
Simon, G.H., von Vopelius-Feldt, J., Wendland, M.F., et al., 2006. MRI of arthritis: Comparison of ultrasmall superparamagnetic iron oxide vs. Gd-DTPA. J Magn Reson Imag 23, 720–727.
Tang, T., Howarth, S.P., Miller, S.R., et al., 2006. Assessment of inflammatory burden contralateral to the symptomatic carotid stenosis using high-resolution ultrasmall, superparamagnetic iron oxide-enhanced MRI. Stroke 37, 2266–2270.
Tedgui, A., Mallat, Z., 2006. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 86, 515–581.
Trivedi, R.A., U-King-Im, J.M., Graves, M.J., et al., 2004. In vivo detection of macrophages in human carotid atheroma: temporal dependence of ultrasmall super-paramagnetic particles of iron oxide-enhanced MRI. Stroke 35, 1631–1635.
Trivedi, R.A., Mallawarachi, C., U-King-Im, J.M., et al., 2006. Identifying Inflamed Carotid Plaques Using In Vivo USPIO-Enhanced MR Imaging to Label Plaque Macrophages. Arterioscler Thromb Vasc Biol 26, 1601–1606.
Tsourkas, A., Shinde-Patil, V.R., Kelly, K.A., et al., 2005. In vivo imaging of activated endothelium using an anti-VCAM-1 magnetooptical probe. Bioconjug Chem 16, 576–581.
Wang, Y.X., Hussain, S.M., Krestin, G.P., 2001. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11, 2319–2331.
Weissleder, R., Lee, A.S., Khaw, B.A., et al., 1992. Antimyosin-labeled monocrystalline iron oxide allows detection of myocardial infarct: MR antibody imaging. Radiology 182, 381–385.
Weissleder, R., Kelly, K., Sun, E.Y., et al., 2005. Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol 23, 1418–1423.
Yancy, A.D., Olzinski, A.R., Hu, T.C., et al., 2005. Differential uptake of ferumoxtran-10 and ferumoxytol, ultrasmall superparamagnetic iron oxide contrast agents in rabbit: critical determinants of atherosclerotic plaque labeling. J Magn Reson Imag 21, 432–442.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Kooi, M., Heeneman, S., Daemen, M., Engelshoven, J.v., Cleutjens, K. (2008). The Emerging Role of USPIOs for MR Imaging of Atherosclerosis. In: Bulte, J.W., Modo, M.M. (eds) Nanoparticles in Biomedical Imaging. Fundamental Biomedical Technologies, vol 102. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72027-2_5
Download citation
DOI: https://doi.org/10.1007/978-0-387-72027-2_5
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-72026-5
Online ISBN: 978-0-387-72027-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)