Emergence of targeted molecular imaging in atherosclerotic cardiovascular disease

Atherosclerosis, a systemic disease, remains one of the leading causes of morbidity and mortality in the world. Our improved understanding of the molecular mechanisms underlying atherosclerotic lesion progression and sudden transformation into unstable plaques, indicate complex interactions of lipid metabolism, inflammatory processes and genetic predisposition. Currently, novel imaging approaches to visualize the process of atherosclerosis, particularly at the molecular level, are actively being developed. Important targets include inflammatory and endothelial cells, as well as apoptosis and angiogenesis. The next decade should solidify the role of targeted molecular imaging in all aspects of cardiovascular medicine.

[1]  S E Nissen,et al.  Extent and direction of arterial remodeling in stable versus unstable coronary syndromes : an intravascular ultrasound study. , 2000, Circulation.

[2]  R. Virmani,et al.  Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. , 1997, The New England journal of medicine.

[3]  Jason L Johnson,et al.  Characteristics of Intact and Ruptured Atherosclerotic Plaques in Brachiocephalic Arteries of Apolipoprotein E Knockout Mice , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[4]  E. Tuzcu,et al.  Relation of matrix-metalloproteinase 3 found in coronary lesion samples retrieved by directional coronary atherectomy to intravascular ultrasound observations on coronary remodeling. , 2002, The American journal of cardiology.

[5]  Ora Israel,et al.  Evaluation of 18F-FDG uptake and arterial wall calcifications using 18F-FDG PET/CT. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (2). , 1992, The New England journal of medicine.

[7]  D M Shames,et al.  MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlation. , 2001, Radiology.

[8]  Zahi A Fayad,et al.  Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography , 2007, Nature Medicine.

[9]  Eric J Topol,et al.  Future use of genomics in coronary artery disease. , 2007, Journal of the American College of Cardiology.

[10]  M. Hori,et al.  Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study. , 2001, Journal of the American College of Cardiology.

[11]  M. Davies,et al.  Relationship Between Coronary Artery Remodeling and Plaque Vulnerability , 2002, Circulation.

[12]  J. Pickard,et al.  Imaging Atherosclerotic Plaque Inflammation With [18F]-Fluorodeoxyglucose Positron Emission Tomography , 2002, Circulation.

[13]  D G Vince,et al.  Arterial remodeling and coronary artery disease: the concept of "dilated" versus "obstructive" coronary atherosclerosis. , 2001, Journal of the American College of Cardiology.

[14]  P. Doevendans,et al.  Visualisation of cell death in vivo in patients with acute myocardial infarction , 2000, The Lancet.

[15]  E. Warburton,et al.  Correlation of Carotid Atheromatous Plaque Inflammation Using USPIO-Enhanced MR Imaging With Degree of Luminal Stenosis , 2008, Stroke.

[16]  S M Jorgensen,et al.  Three-dimensional imaging of vasculature and parenchyma in intact rodent organs with X-ray micro-CT. , 1998, The American journal of physiology.

[17]  P. Rüegsegger,et al.  Morphometric analysis of human bone biopsies: a quantitative structural comparison of histological sections and micro-computed tomography. , 1998, Bone.

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

[19]  R. Bohle,et al.  Atherosclerotic lesions at micro CT: feasibility for analysis of coronary artery wall in autopsy specimens. , 2004, Radiology.

[20]  Claudio Napoli,et al.  Antioxidant Intervention Attenuates Myocardial Neovascularization in Hypercholesterolemia , 2004, Circulation.

[21]  Williams Jk,et al.  The vasa vasorum of the arteries , 1996 .

[22]  E. Ritman,et al.  Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia. , 2001, Cardiovascular research.

[23]  M. Davies,et al.  Atherosclerosis: what is it and why does it occur? , 1993, British heart journal.

[24]  J F Cornhill,et al.  Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. , 1999, JAMA.

[25]  Ralph Weissleder,et al.  Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis , 2006, Circulation.

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

[27]  Jain Kk,et al.  Nanodiagnostics: application of nanotechnology in molecular diagnostics , 2003, Expert review of molecular diagnostics.

[28]  H. Strauss,et al.  Detection of Monocyte Chemoattractant Protein-1 Receptor Expression in Experimental Atherosclerotic Lesions: An Autoradiographic Study , 2001, Circulation.

[29]  V. Poon,et al.  In vitro cytotoxity of silver: implication for clinical wound care. , 2004, Burns : journal of the International Society for Burn Injuries.

[30]  E. Topol,et al.  Mutation of MEF2A in an Inherited Disorder with Features of Coronary Artery Disease , 2003, Science.

[31]  Ahmed Tawakol,et al.  In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. , 2006, Journal of the American College of Cardiology.

[32]  R. Weissleder,et al.  Cellular Imaging of Inflammation in Atherosclerosis Using Magnetofluorescent Nanomaterials , 2006, Molecular imaging.

[33]  E. Tuzcu,et al.  Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease , 2005 .

[34]  E. Ritman,et al.  Cryostatic micro-computed tomography imaging of arterial wall perfusion. , 2002, Scanning.

[35]  R. Poston,et al.  Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. , 1994, The American journal of pathology.

[36]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (1). , 1992, The New England journal of medicine.

[37]  C-Reactive Protein Levels and Outcomes after Statin Therapy , 2005 .

[38]  Chun Yuan,et al.  Quantitative Magnetic Resonance Imaging Analysis of Neovasculature Volume in Carotid Atherosclerotic Plaque , 2003, Circulation.

[39]  G. Pasterkamp,et al.  Multiple complex coronary plaques in patients with acute myocardial infarction. , 2001, The New England journal of medicine.

[40]  Renu Virmani,et al.  Morphological Predictors of Arterial Remodeling in Coronary Atherosclerosis , 2002, Circulation.

[41]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

[42]  Khawar Gul,et al.  Vasa vasorum imaging: A new window to the clinical detection of vulnerable atherosclerotic plaques , 2005, Current atherosclerosis reports.

[43]  Masatoshi Ishibashi,et al.  Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. , 2006, Journal of the American College of Cardiology.

[44]  A. Salinaro,et al.  Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients , 1997, FEBS letters.

[45]  Vasilis Ntziachristos,et al.  In Vivo Imaging of Proteolytic Activity in Atherosclerosis , 2002, Circulation.

[46]  Steven E. Nissen,et al.  High Prevalence of Coronary Atherosclerosis in Asymptomatic Teenagers and Young Adults: Evidence From Intravascular Ultrasound , 2001, Circulation.

[47]  Kyung-Han Lee,et al.  Radiolabeled RGD uptake and alphav integrin expression is enhanced in ischemic murine hindlimbs. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[48]  Erik L. Ritman,et al.  Evaluation of microvascular anatomy by micro-CT , 1999, Herz.

[49]  J. Willerson,et al.  E2F-1 Regulates Nuclear Factor-&kgr;B Activity and Cell Adhesion: Potential Antiinflammatory Activity of the Transcription Factor E2F-1 , 2002, Circulation.

[50]  F. Blankenberg,et al.  Annexin-V imaging for noninvasive detection of cardiac allograft rejection , 2001, Nature Medicine.

[51]  E L Ritman,et al.  Altered Myocardial Microvascular 3D Architecture in Experimental Hypercholesterolemia , 2000, Circulation.

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

[53]  P. Lam,et al.  In vitro cytotoxicity testing of a nanocrystalline silver dressing (Acticoat) on cultured keratinocytes , 2004, British journal of biomedical science.

[54]  J. Isner,et al.  Cancer and atherosclerosis: the broad mandate of angiogenesis. , 1999, Circulation.

[55]  Erik L Ritman,et al.  Vasa vasorum neovascularization and lesion distribution among different vascular beds in ApoE-/-/LDL-/- double knockout mice. , 2007, Atherosclerosis.

[56]  Claudio Napoli,et al.  Simvastatin Preserves the Structure of Coronary Adventitial Vasa Vasorum in Experimental Hypercholesterolemia Independent of Lipid Lowering , 2002, Circulation.

[57]  W.E. Higgins,et al.  Extraction of the hepatic vasculature in rats using 3-D micro-CT images , 2000, IEEE Transactions on Medical Imaging.

[58]  J E Trebes,et al.  Ultrahigh-Resolution X-ray Tomography , 1994, Science.

[59]  P. Baron,et al.  Exposure to Carbon Nanotube Material: Assessment of Nanotube Cytotoxicity using Human Keratinocyte Cells , 2003, Journal of toxicology and environmental health. Part A.

[60]  Martin J Graves,et al.  Assessment of Inflammatory Burden Contralateral to the Symptomatic Carotid Stenosis Using High-Resolution Ultrasmall, Superparamagnetic Iron Oxide–Enhanced MRI , 2006, Stroke.

[61]  B. Flannery,et al.  Three-Dimensional X-ray Microtomography , 1987, Science.

[62]  Masatoshi Ishibashi,et al.  The prevalence of inflammation in carotid atherosclerosis: analysis with fluorodeoxyglucose-positron emission tomography. , 2007, European heart journal.

[63]  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.

[64]  Z. Fayad,et al.  Evaluation of Matrix Metalloproteinases in Atherosclerosis Using a Novel Noninvasive Imaging Approach , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[65]  S. Feinstein,et al.  The powerful microbubble: from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond. , 2004, American journal of physiology. Heart and circulatory physiology.

[66]  J. James,et al.  Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[67]  T. Imaizumi,et al.  Vascular inflammation evaluated by [18F]-fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome. , 2007, Journal of the American College of Cardiology.

[68]  D. K. Bowen,et al.  Three‐dimensional X‐ray microscopy with accurate registration of tomographic sections , 1989, Journal of microscopy.

[69]  R. Virmani,et al.  Targeting of Apoptotic Macrophages and Experimental Atheroma With Radiolabeled Annexin V: A Technique With Potential for Noninvasive Imaging of Vulnerable Plaque , 2003, Circulation.

[70]  D. Kraitchman,et al.  Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using "positive contrast" magnetic resonance imaging. , 2008, Journal of the American College of Cardiology.

[71]  Ralph Weissleder,et al.  Detection of Vascular Adhesion Molecule-1 Expression Using a Novel Multimodal Nanoparticle , 2005, Circulation research.

[72]  S. Kaul,et al.  Assessment of Endogenous and Therapeutic Arteriogenesis by Contrast Ultrasound Molecular Imaging of Integrin Expression , 2005, Circulation.

[73]  J. Lindner,et al.  Molecular Imaging of Inflammation in Atherosclerosis With Targeted Ultrasound Detection of Vascular Cell Adhesion Molecule-1 , 2007, Circulation.

[74]  Albert J. Sinusas,et al.  Noninvasive Imaging of Angiogenesis With a 99mTc-Labeled Peptide Targeted at &agr;v&bgr;3 Integrin After Murine Hindlimb Ischemia , 2005 .

[75]  R. Virmani,et al.  Noninvasive imaging of atherosclerotic lesions in apolipoprotein E-deficient and low-density-lipoprotein receptor-deficient mice with annexin A5. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[76]  W. O’Neill,et al.  Multiple complex coronary plaques in patients with acute myocardial infarction. , 2000, The New England journal of medicine.

[77]  H. Adelsberger,et al.  Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells. , 1998, Circulation.

[78]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[79]  R. Wahl,et al.  Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG) , 2001, Nuclear medicine communications.

[80]  Ralph Weissleder,et al.  Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis , 2008, Circulation.

[81]  P. Libby Inflammation in atherosclerosis , 2002, Nature.

[82]  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.

[83]  P. Libby,et al.  Pathophysiology of Coronary Artery Disease , 2005, Circulation.

[84]  E L Ritman,et al.  Three-dimensional microcomputed tomography of renal vasculature in rats. , 1998, Hypertension.

[85]  H. Sinzinger,et al.  Radiolabelling autologous monocytes with 111-indium-oxine for reinjection in patients with atherosclerosis. , 1990, Progress in clinical and biological research.

[86]  N. Narula,et al.  99mTc-annexin V imaging for in vivo detection of atherosclerotic lesions in porcine coronary arteries. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[87]  Dianna D Cody,et al.  In vivo respiratory-gated micro-CT imaging in small-animal oncology models. , 2004, Molecular imaging.

[88]  Z. Galis,et al.  Expansive Arterial Remodeling Is Associated With Increased Neointimal Macrophage Foam Cell Content: The Murine Model of Macrophage-Rich Carotid Artery Lesions , 2002, Circulation.

[89]  Erik L Ritman,et al.  Correlation of Vasa Vasorum Neovascularization and Plaque Progression in Aortas of Apolipoprotein E−/−/Low-Density Lipoprotein−/− Double Knockout Mice , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[90]  F. Crea,et al.  Widespread coronary inflammation in unstable angina. , 2003, The New England journal of medicine.

[91]  S. Sahoo,et al.  Nanotech approaches to drug delivery and imaging. , 2003, Drug discovery today.

[92]  Juan J. Badimon,et al.  Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta: Implications for Plaque Vulnerability , 2004, Circulation.

[93]  G Finet,et al.  Multiple Atherosclerotic Plaque Rupture in Acute Coronary Syndrome: A Three-Vessel Intravascular Ultrasound Study , 2002, Circulation.

[94]  E L Ritman,et al.  Coronary microvascular functional reserve: quantification of long-term changes with electron-beam CT preliminary results in a porcine model. , 2001, Radiology.

[95]  P. Carmeliet Angiogenesis in health and disease , 2003, Nature Medicine.

[96]  E L Ritman,et al.  Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia. , 1998, The Journal of clinical investigation.

[97]  S. Goldstein,et al.  The direct examination of three‐dimensional bone architecture in vitro by computed tomography , 1989, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.