Characterization and molecular detection of atherothrombosis by magnetic resonance—potential tools for individual risk assessment and diagnostics

This review focuses on recent non‐invasive or minimally invasive magnetic resonance (MR) approaches to study atherothrombosis. The potential benefits of combining diverse metabolic information obtained by the variety of MR techniques from tissues in vivo and ex vivo and from body fluids in vitro are also briefly discussed. A well established methodology is available for lipoprotein subclass quantification from plasma by 1H MR spectroscopy providing information for assessing the long‐term risk of atherosclerosis. Multi‐contrast MR imaging in vivo relying on endogenous contrast allows partial characterization of components in atherothrombotic plaques. The use of exogenous contrast agents in MR angiography enhances blood‐tissue contrast and provides functional information on plaque metabolism, improving plaque characterization and assessment of plaque vulnerability by MR imaging. Recent applications of molecular targeted MR imaging have revealed novel opportunities for specific early detection of atherothrombotic processes, such as angiogenesis and accumulation of macrophages. Currently, MR imaging and spectroscopy can produce such metabolic in vivo and in vitro information that in combination could facilitate the screening, identification and follow‐up of cardiovascularly vulnerable patients in research settings. The recent developments imply that in the near future MR techniques will be part of clinical protocols for individual diagnostics in atherothrombosis.

[1]  M. E. Kooi,et al.  Accumulation of Ultrasmall Superparamagnetic Particles of Iron Oxide in Human Atherosclerotic Plaques Can Be Detected by In Vivo Magnetic Resonance Imaging , 2003, Circulation.

[2]  Ralph Weissleder,et al.  Seeing Within: Molecular Imaging of the Cardiovascular System , 2004, Circulation research.

[3]  V. Fuster The evolving role of CT and MRI in atherothrombotic evaluation and management , 2005, Nature Clinical Practice Cardiovascular Medicine.

[4]  Alfons G H Kessels,et al.  Assessment of human atherosclerotic carotid plaque components with multisequence MR imaging: initial experience. , 2005, Radiology.

[5]  Mika Ala-Korpela,et al.  1H NMR spectroscopy of human blood plasma , 1995 .

[6]  T. Bathen,et al.  Quantification of plasma lipids and apolipoproteins by use of proton NMR spectroscopy, multivariate and neural network analysis , 2000, NMR in biomedicine.

[7]  J. Hamilton,et al.  MRI of Atherothrombosis Associated With Plaque Rupture , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[8]  B Hamm,et al.  Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles , 2001, Journal of magnetic resonance imaging : JMRI.

[9]  Chun Yuan,et al.  In Vivo Quantitative Measurement of Intact Fibrous Cap and Lipid-Rich Necrotic Core Size in Atherosclerotic Carotid Plaque: Comparison of High-Resolution, Contrast-Enhanced Magnetic Resonance Imaging and Histology , 2005, Circulation.

[10]  V. Fuster,et al.  Lipid-Rich Atherosclerotic Plaques Detected by Gadofluorine-Enhanced In Vivo Magnetic Resonance Imaging , 2004, Circulation.

[11]  René M. Botnar,et al.  Coronary magnetic resonance angiography for the detection of coronary stenoses. , 2001, The New England journal of medicine.

[12]  René M. Botnar,et al.  Age and Sex Distribution of Subclinical Aortic Atherosclerosis: A Magnetic Resonance Imaging Examination of the Framingham Heart Study , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[13]  Zahi A Fayad,et al.  Recombinant HDL-like nanoparticles: a specific contrast agent for MRI of atherosclerotic plaques. , 2004, Journal of the American Chemical Society.

[14]  R. Koopman,et al.  Predicting coronary heart disease risk using multiple lipid measures. , 2005, The American journal of cardiology.

[15]  Z. Fayad,et al.  In vivo magnetic resonance evaluation of associations between aortic atherosclerosis and both risk factors and coronary artery disease in patients referred for coronary angiography. , 2004, American heart journal.

[16]  Shelton D Caruthers,et al.  Magnetic resonance nanoparticles for cardiovascular molecular imaging and therapy , 2005, Expert review of cardiovascular therapy.

[17]  René M. Botnar,et al.  Three-Dimensional Black-Blood Cardiac Magnetic Resonance Coronary Vessel Wall Imaging Detects Positive Arterial Remodeling in Patients With Nonsignificant Coronary Artery Disease , 2002, Circulation.

[18]  M. Bennett,et al.  Role of apoptosis in atherosclerosis and its therapeutic implications. , 2004, Clinical science.

[19]  J. Slattery,et al.  Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST) , 1998, The Lancet.

[20]  V. Fuster,et al.  Fibrin-targeted contrast agent for improvement of in vivo acute thrombus detection with magnetic resonance imaging. , 2005, Atherosclerosis.

[21]  D. Pennell,et al.  Cardiovascular magnetic resonance , 2001, Heart.

[22]  Antonio Colombo,et al.  From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. , 2003, Circulation.

[23]  René M. Botnar,et al.  In Vivo Magnetic Resonance Imaging of Coronary Thrombosis Using a Fibrin-Binding Molecular Magnetic Resonance Contrast Agent , 2004, Circulation.

[24]  W. Santamore,et al.  Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? , 1988, Circulation.

[25]  S. Kazarian,et al.  Spectroscopic imaging of arteries and atherosclerotic plaques. , 2004, Biopolymers.

[26]  Zahi A Fayad,et al.  Chronic Thrombus Detection With In Vivo Magnetic Resonance Imaging and a Fibrin-Targeted Contrast Agent , 2005, Circulation.

[27]  Risto A. Kauppinen,et al.  1H MRS detects polyunsaturated fatty acid accumulation during gene therapy of glioma: Implications for the in vivo detection of apoptosis , 1999, Nature Medicine.

[28]  W. Kerwin,et al.  Contrast‐enhanced high resolution MRI for atherosclerotic carotid artery tissue characterization , 2002, Journal of magnetic resonance imaging : JMRI.

[29]  Henrik Antti,et al.  Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics , 2003, Nature Medicine.

[30]  L. Shaw,et al.  Atherosclerotic plaque imaging: contemporary role in preventive cardiology. , 2005, Archives of internal medicine.

[31]  V. Fuster,et al.  Technology Insight: targeting of biological molecules for evaluation of high-risk atherosclerotic plaques with magnetic resonance imaging , 2004, Nature Clinical Practice Cardiovascular Medicine.

[32]  Patrick Winter,et al.  Applications of Nanotechnology to Atherosclerosis, Thrombosis, and Vascular Biology , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[33]  S A Wickline,et al.  Novel MRI Contrast Agent for Molecular Imaging of Fibrin: Implications for Detecting Vulnerable Plaques , 2001, Circulation.

[34]  Samuel A. Wickline,et al.  Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With &agr;v&bgr;3-Integrin–Targeted Nanoparticles , 2003 .

[35]  R. Krauss,et al.  Development of a proton nuclear magnetic resonance spectroscopic method for determining plasma lipoprotein concentrations and subspecies distributions from a single, rapid measurement. , 1992, Clinical chemistry.

[36]  Zahi A. Fayad,et al.  Molecular, cellular and functional imaging of atherothrombosis , 2004, Nature Reviews Drug Discovery.

[37]  Zahi A Fayad,et al.  Atherothrombosis and high-risk plaque: part I: evolving concepts. , 2005, Journal of the American College of Cardiology.

[38]  Martin J Graves,et al.  In Vivo Detection of Macrophages in Human Carotid Atheroma: Temporal Dependence of Ultrasmall Superparamagnetic Particles of Iron Oxide–Enhanced MRI , 2004, Stroke.

[39]  Gabriel P. Krestin,et al.  High-Resolution Spiral Computed Tomography Coronary Angiography in Patients Referred for Diagnostic Conventional Coronary Angiography , 2005, Circulation.

[40]  M. Ala-Korpela,et al.  Modified LDL – trigger of atherosclerosis and inflammation in the arterial intima , 2000, Journal of internal medicine.

[41]  Chun Yuan,et al.  Identification of Fibrous Cap Rupture With Magnetic Resonance Imaging Is Highly Associated With Recent Transient Ischemic Attack or Stroke , 2002, Circulation.

[42]  V. Fuster,et al.  MRI and Characterization of Atherosclerotic Plaque: Emerging Applications and Molecular Imaging , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[43]  J. Hamilton,et al.  Quantification of Cholesteryl Esters in Human and Rabbit Atherosclerotic Plaques by Magic-Angle Spinning 13C-NMR , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[44]  J. Loscalzo,et al.  Identification of cholesteryl esters in human carotid atherosclerosis by ex vivo image-guided proton MRS Published, JLR Papers in Press, November 29, 2005. , 2006, Journal of Lipid Research.

[45]  Qian Wang,et al.  Global impairment of brachial, carotid, and aortic vascular function in young smokers: direct quantification by high-resolution magnetic resonance imaging. , 2004, Journal of the American College of Cardiology.

[46]  S. Neubauer,et al.  Quantification and 3D Reconstruction of Atherosclerotic Plaque Components in Apolipoprotein E Knockout Mice Using Ex Vivo High-Resolution MRI , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[47]  M. Van Cauteren,et al.  Assessment of coronary arteries with total study time of less than 30 minutes by using whole-heart coronary MR angiography. , 2005, Radiology.

[48]  Zahi A. Fayad,et al.  Cardiovascular Magnetic Resonance: Established and Emerging Applications , 2004 .

[49]  Zahi A Fayad,et al.  Atherothrombosis and high-risk plaque: Part II: approaches by noninvasive computed tomographic/magnetic resonance imaging. , 2005, Journal of the American College of Cardiology.

[50]  Z. Fayad,et al.  Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging. , 2005, Journal of the American College of Cardiology.

[51]  Cheuk Y. Tang,et al.  Quantification of human atherosclerotic plaques using spatially enhanced cluster analysis of multicontrast‐weighted magnetic resonance images , 2004, Magnetic resonance in medicine.

[52]  J. Debatin,et al.  Detection of Atherosclerotic Plaque With Gadofluorine-Enhanced Magnetic Resonance Imaging , 2003, Circulation.

[53]  Samin K. Sharma,et al.  Noninvasive in vivo human coronary artery lumen and wall imaging using black-blood magnetic resonance imaging. , 2000, Circulation.

[54]  M Ala-Korpela,et al.  1H NMR-based absolute quantitation of human lipoproteins and their lipid contents directly from plasma. , 1994, Journal of lipid research.

[55]  V. Fuster,et al.  Lipid Lowering by Simvastatin Induces Regression of Human Atherosclerotic Lesions: Two Years’ Follow-Up by High-Resolution Noninvasive Magnetic Resonance Imaging , 2002, Circulation.

[56]  F. Epstein,et al.  Magnetic Resonance Imaging Identifies the Fibrous Cap in Atherosclerotic Abdominal Aortic Aneurysm , 2004, Circulation.

[57]  G. Metzger,et al.  Myocardial triglycerides and systolic function in humans: In vivo evaluation by localized proton spectroscopy and cardiac imaging , 2003, Magnetic resonance in medicine.

[58]  V. Fuster,et al.  Sudden cardiac death: mechanisms, therapies and challenges , 2005, Nature Clinical Practice Cardiovascular Medicine.

[59]  René M. Botnar,et al.  In Vivo Molecular Imaging of Acute and Subacute Thrombosis Using a Fibrin-Binding Magnetic Resonance Imaging Contrast Agent , 2004, Circulation.

[60]  Ken Williams,et al.  Nuclear Magnetic Resonance Lipoprotein Abnormalities in Prediabetic Subjects in the Insulin Resistance Atherosclerosis Study , 2005, Circulation.

[61]  Shelton D Caruthers,et al.  Magnetic resonance molecular imaging with nanoparticles , 2004, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[62]  C. Zarins,et al.  Compensatory enlargement of human atherosclerotic coronary arteries. , 1987, The New England journal of medicine.

[63]  B. Gersh,et al.  Controversies in stable coronary artery disease , 2006, The Lancet.

[64]  V. Fuster,et al.  Atherosclerosis regression and TP receptor inhibition: effect of S18886 on plaque size and composition--a magnetic resonance imaging study. , 2005, European heart journal.

[65]  M. Ala-Korpela,et al.  Sphingomyelinase Induces Aggregation and Fusion of Small Very Low–Density Lipoprotein and Intermediate-Density Lipoprotein Particles and Increases Their Retention to Human Arterial Proteoglycans , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[66]  Patrick J. Gaffney,et al.  Quantitative “magnetic resonance immunohistochemistry” with ligand‐targeted 19F nanoparticles , 2004 .

[67]  E. Boerwinkle,et al.  From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. , 2003, Circulation.

[68]  V. Fuster,et al.  13C-NMR spectroscopy of human atherosclerotic lesions. Relation between fatty acid saturation, cholesteryl ester content, and luminal obstruction. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[69]  T P Trouard,et al.  MRI and NMR spectroscopy of the lipids of atherosclerotic plaque in rabbits and humans , 1997, Magnetic resonance in medicine.

[70]  J. Debatin,et al.  Magnetic Resonance Imaging of Atherosclerotic Plaque With Ultrasmall Superparamagnetic Particles of Iron Oxide in Hyperlipidemic Rabbits , 2001, Circulation.

[71]  Zahi A Fayad,et al.  Atherosclerotic lesions in genetically modified mice quantified in vivo by non-invasive high-resolution magnetic resonance microscopy. , 2002, Atherosclerosis.

[72]  M. Pachot-Clouard,et al.  Tissue characterization of atherosclerotic plaque vulnerability by nuclear magnetic resonance. , 2000, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.