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Preclinical models of atherosclerosis. The future of Hybrid PET/MR technology for the early detection of vulnerable plaque

Published online by Cambridge University Press:  08 April 2016

Irene Cuadrado
Affiliation:
Departmentof Physiology, University of Alcala, School of Medicine, Ctra Madrid Barcelona, Km 3,300, 28875 Alcala de Henares, Madrid, Spain
Marta Saura
Affiliation:
Departmentof Physiology, University of Alcala, School of Medicine, Ctra Madrid Barcelona, Km 3,300, 28875 Alcala de Henares, Madrid, Spain
Borja Castejón
Affiliation:
Cardiology Department, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, 28034 Madrid, Spain
Ana María Martin
Affiliation:
Cardiology Department, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, 28034 Madrid, Spain
Irene Herruzo
Affiliation:
Cardiology Department, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, 28034 Madrid, Spain
Nikolaos Balatsos
Affiliation:
Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26, 412 21 Larissa, Greece
Jose Luis Zamorano
Affiliation:
Cardiology Department, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, 28034 Madrid, Spain
Carlos Zaragoza*
Affiliation:
Cardiology Department, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, 28034 Madrid, Spain
*
*Corresponding author: Carlos Zaragoza, Cardiology Department, University Francisco de Vitoria/Hospital Ramón y Cajal, Ctra. Colmenar Viejo, km 9,100, 28034 Madrid, Spain. E-mail: [email protected]

Abstract

Cardiovascular diseases are the leading cause of death in developed countries. The aetiology is currently multifactorial, thus making them very difficult to prevent. Preclinical models of atherothrombotic diseases, including vulnerable plaque-associated complications, are now providing significant insights into pathologies like atherosclerosis, and in combination with the most recent advances in new non-invasive imaging technologies, they have become essential tools to evaluate new therapeutic strategies, with which can forecast and prevent plaque rupture. Positron emission tomography (PET)/computed tomography imaging is currently used for plaque visualisation in clinical and pre-clinical cardiovascular research, albeit with significant limitations. However, the combination of PET and magnetic resonance imaging (MRI) technologies is still the best option available today, as combined PET/MRI scans provide simultaneous data acquisition together with high quality anatomical information, sensitivity and lower radiation exposure for the patient. The coming years may represent a new era for the implementation of PET/MRI in clinical practice, but first, clinically efficient attenuation correction algorithms and research towards multimodal reagents and safety issues should be validated at the preclinical level.

Type
Review
Copyright
Copyright © Cambridge University Press 2016 

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References

1. Altaf, N. et al. (2008) Detection of intraplaque hemorrhage by magnetic resonance imaging in symptomatic patients with mild to moderate carotid stenosis predicts recurrent neurological events. Journal of Vascular Surgery 47, 337-342 Google Scholar
2. Vaina, S. and Stefanadis, C. (2005) Detection of the vulnerable coronary atheromatous plaque. Where are we now? International Journal of Cardiovascular Intervention 7, 75-87 Google Scholar
3. Romero, J.R. et al. (2009) Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: the Framingham study. Stroke 40, 1590-1596 Google Scholar
4. Adams, M.R. and Celermajer, D.S. (1999) Detection of presymptomatic atherosclerosis: a current perspective. Clinical Science (Lond) 97, 615-624 Google Scholar
5. Cocker, M.S. et al. (2012) Imaging atherosclerosis with hybrid [18F]fluorodeoxyglucose positron emission tomography/computed tomography imaging: what Leonardo da Vinci could not see. Journal of Nuclear Cardiology 19, 1211-1225 Google Scholar
6. Davies, J.R. et al. (2005) Targeting the vulnerable plaque: the evolving role of nuclear imaging. Journal of Nuclear Cardiology 12, 234-246 Google Scholar
7. Botnar, R.M. et al. (2015) Molecular imaging in cardiovascular diseases. RoFo 36, 92-101 Google Scholar
8. Sadeghi, M.M. et al. (2010) Imaging atherosclerosis and vulnerable plaque. Journal of Nuclear Medicine 51 (Suppl 1), 51S-65S Google Scholar
9. Vengrenyuk, Y. et al. (2010) Computational stress analysis of atherosclerotic plaques in ApoE knockout mice. Annals of Biomedical Engineering 38, 738-747 CrossRefGoogle ScholarPubMed
10. Canet-Soulas, E. and Letourneur, D. (2007) Biomarkers of atherosclerosis and the potential of MRI for the diagnosis of vulnerable plaque. MAGMA 20, 129-142 Google Scholar
11. Kanwar, R.K. et al. (2012) Emerging engineered magnetic nanoparticulate probes for molecular MRI of atherosclerosis: how far have we come? Nanomedicine (Lond) 7, 899-916 Google Scholar
12. Naghavi, M. et al. (2006) From vulnerable plaque to vulnerable patient – part III: executive summary of the screening for heart attack prevention and education (SHAPE) task force report. American Journal of Cardiology 98, 2H-15H Google Scholar
13. Li, Y. et al. (2008) Effect of aging on fatty streak formation in a diet-induced mouse model of atherosclerosis. Journal of Vascular Research 45, 205-210 Google Scholar
14. Majmudar, M.D. et al. (2013) Polymeric nanoparticle PET/MR imaging allows macrophage detection in atherosclerotic plaques. Circulation Research 112, 755-761 Google Scholar
15. Millon, A. et al. (2014) Animal models of atherosclerosis and magnetic resonance imaging for monitoring plaque progression. Vascular 22, 221-237 Google Scholar
16. Pedersen, S.F. et al. (2014) Feasibility of simultaneous PET/MR in diet-induced atherosclerotic minipig: a pilot study for translational imaging. American Journal of Nuclear Medicine and Molecular Imaging 4, 448-458 Google Scholar
17. Ratib, O. and Nkoulou, R. (2014) Potential applications of PET/MR imaging in cardiology. Journal of Nuclear Medicine 55 (Suppl 2), 40S-46S Google Scholar
18. Rischpler, C., Nekolla, S.G. and Beer, A.J. (2013) PET/MR imaging of atherosclerosis: initial experience and outlook. American Journal of Nuclear Medicine and Molecular Imaging 3, 393-396 Google Scholar
19. Bigalke, B. et al. (2014) PET/CT and MR imaging biomarker of lipid-rich plaques using [64Cu]-labeled scavenger receptor (CD68-Fc). International Journal of Cardiology 177, 287-291 Google Scholar
20. Hatsukami, T.S. et al. (2000) Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging. Circulation 102, 959-964 Google Scholar
21. Jones, G.W. et al. (2015) Imbalanced gp130 signalling in ApoE-deficient mice protects against atherosclerosis. Atherosclerosis 238, 321-328 Google Scholar
22. Xu, L. et al. (2015) Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia. Arteriosclerosis, Thrombosis, and Vascular Biology 35, 1787-1797 Google Scholar
23. Cai, J. et al. (2005) 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. Circulation 112, 3437-3444 CrossRefGoogle ScholarPubMed
24. Heeneman, S. et al. (2008) Control of atherosclerotic plaque vulnerability: insights from transgenic mice. Frontiers in Bioscience 13, 6289-6313 Google Scholar
25. Iqbal, J. et al. (2015) Role of animal models in coronary stenting. Annals of Biomedical Engineering 44, 453-465 Google Scholar
26. Dweck, M.R. et al. (2016) MR imaging of coronary arteries and plaques. JACC: Cardiovascular Imaging 9, 306-316 Google Scholar
27. Mateo, J. et al. (2015) Magnetic resonance imaging of the atherosclerotic mouse aorta. Methods in Molecular Biology 1339, 387-394 Google Scholar
28. U-King-Im, J.M. et al. (2008) Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI. Journal of Neurology, Neurosurgery, and Psychiatry 79, 905-912 Google Scholar
29. Wasserman, B.A. et al. (2002) Carotid artery atherosclerosis: in vivo morphologic characterization with gadolinium-enhanced double-oblique MR imaging initial results. Radiology 223, 566-573 Google Scholar
30. Boshuizen, M.C. et al. (2015) Interferon-β promotes macrophage foam cell formation by altering both cholesterol influx and efflux mechanisms. Cytokine 77, 220-226 Google Scholar
31. Getz, G.S. and Reardon, C.A. (2015) Use of mouse models in atherosclerosis research. Methods in Molecular Biology 1339, 1-16 Google Scholar
32. Li, G. et al. (2015) Hematopoietic knockdown of PPARδ reduces atherosclerosis in LDLR-/- mice. Gene Therapy 23, 78-85 Google Scholar
33. Ru, D. et al. (2015) Oxidized high-density lipoprotein accelerates atherosclerosis progression by inducing the imbalance between treg and teff in LDLR knockout mice. Acta Pathologica, Microbiologica, et Immunologica Scandinavica 123, 410-421 Google Scholar
34. Rensing, K.L. et al. (2014) Akt2/LDLr double knockout mice display impaired glucose tolerance and develop more complex atherosclerotic plaques than LDLr knockout mice. Cardiovascular Research 101, 277-287 CrossRefGoogle ScholarPubMed
35. Marquart, T.J. et al. (2013) Anti-miR-33 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology 33, 455-458 Google Scholar
36. Tang, T. et al. (2013) Prevention of TGFβ induction attenuates angII-stimulated vascular biglycan and atherosclerosis in Ldlr-/- mice. Journal of Lipid Research 54, 2255-2264 Google Scholar
37. Teodoro, B.G. et al. (2012) Improvements of atherosclerosis and hepatic oxidative stress are independent of exercise intensity in LDLr(-/-) mice. Journal of Atherosclerosis and Thrombosis 19, 904-911 Google Scholar
38. Awan, Z. et al. (2011) The LDLR deficient mouse as a model for aortic calcification and quantification by micro-computed tomography. Atherosclerosis 219, 455-462 Google Scholar
39. Zhao, L. et al. (2008) CD44 expressed on both bone marrow-derived and non-bone marrow-derived cells promotes atherogenesis in ApoE-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology 28, 1283-1289 Google Scholar
40. Andrés, V. et al. (2006) Atheroma development in apolipoprotein E-null mice is not affected by partial inactivation of PTEN. Frontiers in Bioscience 11, 2739-2745 Google Scholar
41. Higashimori, M. et al. (2011) Role of toll-like receptor 4 in intimal foam cell accumulation in apolipoprotein E-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology 31, 50-57 Google Scholar
42. Meir, K.S. and Leitersdorf, E. (2004) Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress. Arteriosclerosis, Thrombosis, and Vascular Biology 24, 1006-1014 Google Scholar
43. Bot, I. et al. (2011) Atorvastatin inhibits plaque development and adventitial neovascularization in ApoE deficient mice independent of plasma cholesterol levels. Atherosclerosis 214, 295-300 Google Scholar
44. Akhtar, S. et al. (2013) CXCL12 promotes the stabilization of atherosclerotic lesions mediated by smooth muscle progenitor cells in Apoe-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology 33, 679-686 Google Scholar
45. Fernández-Hernando, C. et al. (2009) Absence of Akt1 reduces vascular smooth muscle cell migration and survival and induces features of plaque vulnerability and cardiac dysfunction during atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 29, 2033-2040 Google Scholar
46. Vaisman, B.L. et al. (2015) Endothelial expression of scavenger receptor class B, type I protects against development of atherosclerosis in mice. BioMed Research International 2015, 607120 CrossRefGoogle Scholar
47. Kitayama, K. et al. (2006) Blockade of scavenger receptor class B type I raises high density lipoprotein cholesterol levels but exacerbates atherosclerotic lesion formation in apolipoprotein E deficient mice. Journal of Pharmacy and Pharmacology 58, 1629-1638 Google Scholar
48. Zhang, S. et al. (2005) Diet-induced occlusive coronary atherosclerosis, myocardial infarction, cardiac dysfunction, and premature death in scavenger receptor class B type I-deficient, hypomorphic apolipoprotein ER61 mice. Circulation 111, 3457-3464 Google Scholar
49. Zhang, W. et al. (2003) Inactivation of macrophage scavenger receptor class B type I promotes atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation 108, 2258-2263 Google Scholar
50. Sosnovik, D.E. and Caravan, P. (2009) Molecular MRI of atherosclerotic plaque with targeted contrast agents. Current Cardiovascular Imaging Reports 2, 87-94 Google Scholar
51. Zadelaar, S. et al. (2007) Mouse models for atherosclerosis and pharmaceutical modifiers. Arteriosclerosis, Thrombosis, and Vascular Biology 27, 1706-1721 Google Scholar
52. Lardenoye, J.H. et al. (2000) Accelerated atherosclerosis by placement of a perivascular cuff and a cholesterol-rich diet in ApoE*3Leiden transgenic mice. Circulation Research 87, 248-253 Google Scholar
53. Lalloyer, F. et al. (2011) Peroxisome proliferator-activated receptor-alpha gene level differently affects lipid metabolism and inflammation in apolipoprotein E2 knock-in mice. Arteriosclerosis, Thrombosis, and Vascular Biology 31, 1573-1579 Google Scholar
54. Johnson, J. et al. (2005) Plaque rupture after short periods of fat feeding in the apolipoprotein E-knockout mouse: model characterization and effects of pravastatin treatment. Circulation 111, 1422-1430 Google Scholar
55. Katsuki, S. et al. (2014) Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque destabilization/rupture in mice by regulating the recruitment of inflammatory monocytes. Circulation 129, 896-906 Google Scholar
56. Matoba, T., Sato, K. and Egashira, K. (2013) Mouse models of plaque rupture. Current Opinion in Lipidology 24, 419-425 Google Scholar
57. Sato, K. et al. (2012) Dietary cholesterol oxidation products accelerate plaque destabilization and rupture associated with monocyte infiltration/activation via the MCP-1-CCR2 pathway in mouse brachiocephalic arteries: therapeutic effects of ezetimibe. Journal of Atherosclerosis and Thrombosis 19, 986-998 CrossRefGoogle ScholarPubMed
58. Gough, P.J. et al. (2006) Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice. Journal of Clinical Investigation 116, 59-69 Google Scholar
59. Hu, J.H. et al. (2010) Overexpression of urokinase by plaque macrophages causes histological features of plaque rupture and increases vascular matrix metalloproteinase activity in aged apolipoprotein e-null mice. Circulation 121, 1637-1644 Google Scholar
60. Ma, T. et al. (2013) Th17 cells and IL-17 are involved in the disruption of vulnerable plaques triggered by short-term combination stimulation in apolipoprotein E-knockout mice. Cellular & Molecular Immunology 10, 338-348 Google Scholar
61. de Witt, S.M. et al. (2014) Insights into platelet-based control of coagulation. Thrombosis Research 133 (Suppl 2), S139-S148 Google Scholar
62. Desai, M.Y. and Lima, J.A. (2006) Imaging of atherosclerosis using magnetic resonance: state of the art and future directions. Current Atherosclerosis Reports 8, 131-139 Google Scholar
63. Momiyama, Y. and Fayad, Z.A. (2007) Aortic plaque imaging and monitoring atherosclerotic plaque interventions. Topics in Magnetic Resonance Imaging 18, 349-355 Google Scholar
64. Yonemura, A. et al. (2009) Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques: a 2-year follow-up by noninvasive MRI. European Journal of Cardiovascular Prevention and Rehabilitation 16, 222-228 Google Scholar
65. Blum, A. and Nahir, M. (2013) Future non-invasive imaging to detect vascular plaque instability and subclinical non-obstructive atherosclerosis. Journal of Geriatric Cardiology 10, 178-185 Google Scholar
66. Oikawa, M. et al. (2009) Carotid magnetic resonance imaging. A window to study atherosclerosis and identify high-risk plaques. Circulation Journal 73, 1765-1773 Google Scholar
67. Raman, S.V. et al. (2008) In vivo atherosclerotic plaque characterization using magnetic susceptibility distinguishes symptom-producing plaques. JACC Cardiovascular Imaging 1, 49-57 Google Scholar
68. Slevin, M. et al. (2010) Combining nanotechnology with current biomedical knowledge for the vascular imaging and treatment of atherosclerosis. Molecular Biosystems 6, 444-450 Google Scholar
69. Winter, P.M. et al. (2003) Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles. Circulation 108, 2270-2274 Google Scholar
70. Cheng, K.K. et al. (2010) Metabolomic study of the LDL receptor null mouse fed a high-fat diet reveals profound perturbations in choline metabolism that are shared with ApoE null mice. Physiological Genomics 41, 224-231 Google Scholar
71. Abran, M. et al. (2015) Validating a bimodal intravascular ultrasound (IVUS) and near-infrared fluorescence (NIRF) catheter for atherosclerotic plaque detection in rabbits. Biomedical Optics Express 6, 3989-3999 Google Scholar
72. El-Sheakh, A.R. et al. (2015) Antioxidant and anti-inflammatory effects of flavocoxid in high-cholesterol-fed rabbits. Naunyn-Schmiedeberg's Archives of Pharmacology 388, 1333-1344 Google Scholar
73. Fan, J. et al. (2015) Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine. Pharmacology & Therapeutics 146, 104-119 Google Scholar
74. Hyafil, F. et al. (2015) Detection of apoptotic cells in a rabbit model with atherosclerosis-like lesions using the positron emission tomography radiotracer [18F]ML-10. Molecular Imaging 14, 433-442 Google Scholar
75. Fang, D. et al. (2014) Atorvastatin suppresses Toll-like receptor 4 expression and NF-κB activation in rabbit atherosclerotic plaques. European Review for Medical and Pharmacological Sciences 18, 242-246 Google ScholarPubMed
76. Kong, L. et al. (2013) The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits. Lipids in Health and Disease 12, 115 Google Scholar
77. Millon, A. et al. (2013) Monitoring plaque inflammation in atherosclerotic rabbits with an iron oxide (P904) and (18)F-FDG using a combined PET/MR scanner. Atherosclerosis 228, 339-345 Google Scholar
78. Shiomi, M., Koike, T. and Ito, T. (2013) Contribution of the WHHL rabbit, an animal model of familial hypercholesterolemia, to elucidation of the anti-atherosclerotic effects of statins. Atherosclerosis 231, 39-47 Google Scholar
79. Tian, J. et al. (2013) Vasa vasorum and plaque progression, and responses to atorvastatin in a rabbit model of atherosclerosis: contrast-enhanced ultrasound imaging and intravascular ultrasound study. Heart 99, 48-54 Google Scholar
80. Yanni, A.E. (2004) The laboratory rabbit: an animal model of atherosclerosis research. Laboratory Animals 38, 246-256 Google Scholar
81. Johnstone, M.T. et al. (2001) In vivo magnetic resonance imaging of experimental thrombosis in a rabbit model. Arteriosclerosis, Thrombosis, and Vascular Biology 21, 1556-1560 Google Scholar
82. Shukla, K. et al. (2014) Hypolipidemic and antioxidant activity of aqueous extract of fruit of Withania coagulans (Stocks) Dunal in cholesterol-fed hyperlipidemic rabbit model. Indian Journal of Experimental Biology 52, 870-875 Google Scholar
83. Yang, X. et al. (2006) Effects of simvastatin on NF-kappaB-DNA binding activity and monocyte chemoattractant protein-1 expression in a rabbit model of atherosclerosis. Journal of Huazhong University of Science and Technology 26, 194-198 Google Scholar
84. Helft, G. et al. (2002) Progression and regression of atherosclerotic lesions: monitoring with serial noninvasive magnetic resonance imaging. Circulation 105, 993-998 Google Scholar
85. Rival, Y. et al. (2002) Anti-atherosclerotic properties of the acyl-coenzyme A: cholesterol acyltransferase inhibitor F 12511 in casein-fed New Zealand rabbits. Journal of Cardiovascular Pharmacology 39, 181-191 Google Scholar
86. Tijburg, L.B. et al. (1997) Effects of green tea, black tea and dietary lipophilic antioxidants on LDL oxidizability and atherosclerosis in hypercholesterolaemic rabbits. Atherosclerosis 135, 37-47 Google Scholar
87. Largo, R. et al. (2008) Chronic arthritis aggravates vascular lesions in rabbits with atherosclerosis: a novel model of atherosclerosis associated with chronic inflammation. Arthritis and Rheumatism 58, 2723-2734 Google Scholar
88. Zhao, Q.M. et al. (2013) Detection of vulnerable atherosclerotic plaque and prediction of thrombosis events in a rabbit model using 18F-FDG -PET/CT. PLoS ONE 8, e61140 Google Scholar
89. Phinikaridou, A. et al. (2010) In vivo detection of vulnerable atherosclerotic plaque by MRI in a rabbit model. Circulation Cardiovascular Imaging 3, 323-332 Google Scholar
90. Shimizu, T. et al. (2009) Simple rabbit model of vulnerable atherosclerotic plaque. Neurologia medico-chirurgica (Tokyo) 49, 327-332; discussion 32Google Scholar
91. Abela, G.S. et al. (1995) Triggering of plaque disruption and arterial thrombosis in an atherosclerotic rabbit model. Circulation 91, 776-784 Google Scholar
92. Zhang, J. et al. (2012) Endothelial lipase mediates HDL levels in normal and hyperlipidemic rabbits. Journal of Atherosclerosis and Thrombosis 19, 213-226 Google Scholar
93. Ito, T. and Shiomi, M. (2001) Cerebral atherosclerosis occurs spontaneously in homozygous WHHL rabbits. Atherosclerosis 156, 57-66 Google Scholar
94. Mohler, E.R. et al. (2008) Site-specific atherogenic gene expression correlates with subsequent variable lesion development in coronary and peripheral vasculature. Arteriosclerosis, Thrombosis, and Vascular Biology 28, 850-855 Google Scholar
95. Gerrity, R.G. et al. (2001) Diabetes-induced accelerated atherosclerosis in swine. Diabetes 50, 1654-1665 Google Scholar
96. Hamada, N. et al. (2010) Tacrolimus-eluting stent inhibits neointimal hyperplasia via calcineurin/NFAT signaling in porcine coronary artery model. Atherosclerosis 208, 97-103 Google Scholar
97. Behler, R.H. et al. (2009) ARFI imaging for noninvasive material characterization of atherosclerosis. Part II: toward in vivo characterization. Ultrasound in Medicine & Biology 35, 278-295 Google Scholar
98. Deuse, T. et al. (2014) Dichloroacetate prevents restenosis in preclinical animal models of vessel injury. Nature 509, 641-644 Google Scholar
99. Virmani, R., Kolodgie, F.D. and Farb, A. (2004) Drug-eluting stents: are they really safe? American Heart Hospital Journal 2, 85-88 Google Scholar
100. Beller, G.A. (2008) Cardiovascular molecular imaging: where art thou? Journal of Nuclear Cardiology 15, 611-612 Google Scholar
101. Nörenberg, D. et al. (2015) Molecular magnetic resonance imaging of atherosclerotic vessel wall disease. European Radiology 26, 910-920 Google Scholar
102. Phinikaridou, A. et al. (2013) Molecular MRI of atherosclerosis. Molecules 18, 14042-14069 CrossRefGoogle ScholarPubMed
103. Misri, R., Saatchi, K. and Häfeli, U.O. (2012) Nanoprobes for hybrid SPECT/MR molecular imaging. Nanomedicine (Lond) 7, 719-733 Google Scholar
104. Chen, W. et al. (2011) Nanoparticles as magnetic resonance imaging contrast agents for vascular and cardiac diseases. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 3, 146-161 Google Scholar
105. Klink, A. et al. (2010) Magnetic resonance molecular imaging of thrombosis in an arachidonic acid mouse model using an activated platelet targeted probe. Arteriosclerosis, Thrombosis, and Vascular Biology 30, 403-410 Google Scholar
106. Mulder, W.J. et al. (2008) Multimodality nanotracers for cardiovascular applications. Nature Clinical Practice. Cardiovascular Medicine 5 (Suppl 2), S103-S111 Google Scholar
107. Yuan, C. et al. (1998) Measurement of atherosclerotic carotid plaque size in vivo using high resolution magnetic resonance imaging. Circulation 98, 2666-2671 Google Scholar
108. Stuber, M. et al. (1999) Submillimeter three-dimensional coronary MR angiography with real-time navigator correction: comparison of navigator locations. Radiology 212, 579-587 Google Scholar
109. Worthley, S.G. et al. (2000) Noninvasive in vivo magnetic resonance imaging of experimental coronary artery lesions in a porcine model. Circulation 101, 2956-2961 Google Scholar
110. Fayad, Z.A. et al. (2000) Noninvasive in vivo human coronary artery lumen and wall imaging using black-blood magnetic resonance imaging. Circulation 102, 506-510 Google Scholar
111. Corti, R. et al. (2001) New understanding of atherosclerosis (clinically and experimentally) with evolving MRI technology in vivo. Annals of the New York Academy of Sciences 947, 181-195 Google Scholar
112. Yuan, C. et al. (2001) In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques. Circulation 104, 2051-2056 Google Scholar
113. Corti, R. et al. (2002) Effect of percutaneous transluminal angioplasty on severely stenotic femoral lesions: in vivo demonstration by noninvasive magnetic resonance imaging. Circulation 106, 1570-1571 Google Scholar
114. Yuan, C. et al. (2002) Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke. Circulation 105, 181-185 Google Scholar
115. Kramer, C.M. (2015) Novel magnetic resonance imaging end points for physiologic studies in peripheral arterial disease: elegance versus practicality. Circulation Cardiovascular Imaging 8, pii: e003360CrossRefGoogle ScholarPubMed
116. Di Leo, G. et al. (2015) Diagnostic accuracy of magnetic resonance angiography for detection of coronary artery disease: a systematic review and meta-analysis. European Radiology, 1-13 [Epub ahead of print]Google Scholar
117. Makowski, M.R. et al. (2009) Molecular imaging with targeted contrast agents. Topics in Magnetic Resonance Imaging 20, 247-259 Google Scholar
118. Mulder, W.J. et al. (2007) Magnetic resonance molecular imaging contrast agents and their application in atherosclerosis. Topics in Magnetic Resonance Imaging 18, 409-417 Google Scholar
119. Segers, F.M. et al. (2013) Scavenger receptor-AI-targeted iron oxide nanoparticles for in vivo MRI detection of atherosclerotic lesions. Arteriosclerosis, Thrombosis, and Vascular Biology 33, 1812-1819 Google Scholar
120. Metz, S. et al. (2011) Characterization of carotid artery plaques with USPIO-enhanced MRI: assessment of inflammation and vascularity as in vivo imaging biomarkers for plaque vulnerability. International Journal of Cardiovascular Imaging 27, 901-912 Google Scholar
121. Klug, G., Bauer, L. and Bauer, W.R. (2008) Patterns of USPIO deposition in murine atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 28, E157; author reply E58-E59Google Scholar
122. Ma, Z.L. et al. (2009) Inhibited atherosclerotic plaque formation by local administration of magnetically labeled endothelial progenitor cells (EPCs) in a rabbit model. Atherosclerosis 205, 80-86 Google Scholar
123. Sigovan, M. et al. (2009) Rapid-clearance iron nanoparticles for inflammation imaging of atherosclerotic plaque: initial experience in animal model. Radiology 252, 401-409 Google Scholar
124. Bjerner, T. et al. (2000) Evaluation of nonperfused myocardial ischemia with MRI and an intravascular USPIO contrast agent in an ex vivo pig model. Journal of Magnetic Resonance Imaging 12, 866-872 Google Scholar
125. Sigovan, M. et al. (2012) Anti-inflammatory drug evaluation in ApoE-/- mice by ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging. Investigative Radiology 47, 546-552 Google Scholar
126. Jacobin-Valat, M.J. et al. (2011) MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis. NMR in Biomedicine 24, 413-424 Google Scholar
127. Burtea, C. et al. (2008) Molecular imaging of alpha v beta3 integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA. Cardiovascular Research 78, 148-157 Google Scholar
128. McAteer, M.A. et al. (2012) A leukocyte-mimetic magnetic resonance imaging contrast agent homes rapidly to activated endothelium and tracks with atherosclerotic lesion macrophage content. Arteriosclerosis, Thrombosis, and Vascular Biology 32, 1427-1435 Google Scholar
129. Tang, T.Y. et al. (2009) The ATHEROMA (atorvastatin therapy: effects on reduction of macrophage activity) study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. Journal of the American College of Cardiology 53, 2039-2050 Google Scholar
130. Diwoky, C. et al. (2015) Positive contrast of SPIO-labeled cells by off-resonant reconstruction of 3D radial half-echo bSSFP. NMR in Biomedicine 28, 79-88 Google Scholar
131. Almer, G. et al. (2013) Interleukin-10: an anti-inflammatory marker to target atherosclerotic lesions via PEGylated liposomes. Molecular Pharmaceutics 10, 175-186 Google Scholar
132. Hansen, T. et al. (2009) Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population. Atherosclerosis 205, 163-167 CrossRefGoogle Scholar
133. Andia, M.E. et al. (2014) Fibrin-targeted magnetic resonance imaging allows in vivo quantification of thrombus fibrin content and identifies thrombi amenable for thrombolysis. Arteriosclerosis, Thrombosis, and Vascular Biology 34, 1193-1198 Google Scholar
134. Chen, W. et al. (2013) Collagen-specific peptide conjugated HDL nanoparticles as MRI contrast agent to evaluate compositional changes in atherosclerotic plaque regression. JACC Cardiovascular Imaging 6, 373-384 CrossRefGoogle ScholarPubMed
135. Spuentrup, E. et al. (2009) Molecular magnetic resonance imaging of myocardial perfusion with EP-3600, a collagen-specific contrast agent: initial feasibility study in a swine model. Circulation 119, 1768-1775 Google Scholar
136. Phinikaridou, A. et al. (2014) Vascular remodeling and plaque vulnerability in a rabbit model of atherosclerosis: comparison of delayed-enhancement MR imaging with an elastin-specific contrast agent and unenhanced black-blood MR imaging. Radiology 271, 390-399 Google Scholar
137. Hyafil, F. et al. (2011) Monitoring of arterial wall remodelling in atherosclerotic rabbits with a magnetic resonance imaging contrast agent binding to matrix metalloproteinases. European Heart Journal 32, 1561-1571 Google Scholar
138. Liu, Y. et al. (2013) PET imaging of chemokine receptors in vascular injury-accelerated atherosclerosis. Journal of Nuclear Medicine 54, 1135-1141 Google Scholar
139. Tawakol, A. et al. (2013) Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. Journal of the American College of Cardiology 62, 909-917 Google Scholar
140. Hag, A.M. et al. (2012) (18)F-FDG PET imaging of murine atherosclerosis: association with gene expression of key molecular markers. PLoS ONE 7, e50908 Google Scholar
141. Rosenbaum, D., Millon, A. and Fayad, Z.A. (2012) Molecular imaging in atherosclerosis: FDG PET. Current Atherosclerosis Reports 14, 429-437 Google Scholar
142. Calcagno, C. et al. (2008) Detection of neovessels in atherosclerotic plaques of rabbits using dynamic contrast enhanced MRI and 18F-FDG PET. Arteriosclerosis, Thrombosis, and Vascular Biology 28, 1311-1317 Google Scholar
143. Rudd, J.H. et al. (2008) Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. Journal of Nuclear Medicine 49, 871-878 Google Scholar
144. Rudd, J.H. et al. (2007) (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. Journal of the American College of Cardiology 50, 892-896 Google Scholar
145. Chen, W. and Dilsizian, V. (2013) Targeted PET/CT imaging of vulnerable atherosclerotic plaques: microcalcification with sodium fluoride and inflammation with fluorodeoxyglucose. Current Cardiology Reports 15, 364 Google Scholar
146. Tawakol, A. et al. (2005) Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. Journal of Nuclear Cardiology 12, 294-301 Google Scholar
147. Vucic, E. et al. (2012) Regression of inflammation in atherosclerosis by the LXR agonist R211945: a noninvasive assessment and comparison with atorvastatin. JACC Cardiovascular Imaging 5, 819-828 Google Scholar
148. Davies, J.R. et al. (2010) FDG-PET can distinguish inflamed from non-inflamed plaque in an animal model of atherosclerosis. International Journal of Cardiovascular Imaging 26, 41-48 Google Scholar
149. Ogawa, M. et al. (2006) Application of 18F-FDG PET for monitoring the therapeutic effect of anti-inflammatory drugs on stabilization of vulnerable atherosclerotic plaques. Journal of Nuclear Medicine 47, 1845-1850 Google Scholar
150. Vucic, E. et al. (2011) Pioglitazone modulates vascular inflammation in atherosclerotic rabbits noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging. JACC Cardiovascular Imaging 4, 1100-1109 Google Scholar
151. Lobatto, M.E. et al. (2012) Imaging the efficacy of anti-inflammatory liposomes in a rabbit model of atherosclerosis by non-invasive imaging. Methods in Enzymology 508, 211-228 Google Scholar
152. Laitinen, I. et al. (2009) Uptake of inflammatory cell marker [11C]PK11195 into mouse atherosclerotic plaques. European Journal of Nuclear Medicine and Molecular Imaging 36, 73-80 Google Scholar
153. Gaemperli, O. et al. (2012) Imaging intraplaque inflammation in carotid atherosclerosis with 11C-PK11195 positron emission tomography/computed tomography. European Heart Journal 33, 1902-1910 Google Scholar
154. Matter, C.M. et al. (2006) 18F-choline images murine atherosclerotic plaques ex vivo. Arteriosclerosis, Thrombosis, and Vascular Biology 26, 584-589 Google Scholar
155. Nahrendorf, M. et al. (2008) Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation 117, 379-387 Google Scholar
156. Libby, P., DiCarli, M. and Weissleder, R. (2010) The vascular biology of atherosclerosis and imaging targets. Journal of Nuclear Medicine 51 (Suppl 1), 33S-37S Google Scholar
157. Nahrendorf, M. et al. (2009) 18F-4V for PET-CT imaging of VCAM-1 expression in atherosclerosis. JACC Cardiovascular Imaging 2, 1213-1222 Google Scholar
158. Silvola, J.M. et al. (2011) Detection of hypoxia by [18F]EF5 in atherosclerotic plaques in mice. Arteriosclerosis, Thrombosis, and Vascular Biology 31, 1011-1015 Google Scholar
159. Laitinen, I. et al. (2009) Evaluation of alphavbeta3 integrin-targeted positron emission tomography tracer 18F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice. Circulation Cardiovascular Imaging 2, 331-338 Google Scholar
160. Elmaleh, D.E. et al. (2006) Detection of inflamed atherosclerotic lesions with diadenosine-5″,5‴-P1′,P4-tetraphosphate (Ap4A) and positron-emission tomography. Proceedings of the National Academy of Sciences of the United States of America 103, 15992-15996 Google Scholar
161. Liu, Y. et al. (2010) Molecular imaging of atherosclerotic plaque with (64)Cu-labeled natriuretic peptide and PET. Journal of Nuclear Medicine 51, 85-91 Google Scholar
162. Derlin, T. et al. (2011) Feasibility of 11C-acetate PET/CT for imaging of fatty acid synthesis in the atherosclerotic vessel wall. Journal of Nuclear Medicine 52, 1848-1854 Google Scholar
163. Zerhouni, E.A. (1990) New directions in cardiac magnetic resonance imaging. Topics in Magnetic Resonance Imaging 2, 67-71 Google Scholar
164. Skorton, D.J. and Collins, S.M. (1985) New directions in cardiac imaging. Annals of Internal Medicine 102, 795-799 Google Scholar
165. Bailey, D.L. et al. (2015) Combined PET/MRI: multi-modality multi-parametric imaging is here: summary report of the 4th international workshop on PET/MR imaging; February 23-27, 2015, Tübingen, Germany. Molecular Imaging and Biology 17, 595-608 Google Scholar
166. Delso, G., Ter Voert, E. and Veit-Haibach, P. (2015) How does PET/MR work? Basic physics for physicians. Abdominal Imaging 40, 1352-1357 Google Scholar
167. Disselhorst, J.A. et al. (2014) Principles of PET/MR imaging. Journal of Nuclear Medicine 55 (Suppl 2), 2S-10S Google Scholar
168. Martinez-Möller, A. et al. (2007) Dual cardiac-respiratory gated PET: implementation and results from a feasibility study. European Journal of Nuclear Medicine and Molecular Imaging 34, 1447-1454 Google Scholar
169. Martinez-Möller, A. and Nekolla, S.G. (2012) Attenuation correction for PET/MR: problems, novel approaches and practical solutions. Zeitschrift fur Medizinische Physik 22, 299-310 Google Scholar
170. Nappi, C. and El Fakhri, G. (2013) State of the art in cardiac hybrid technology: PET/MR. Current Cardiovascular Imaging Reports 6, 338-345 Google Scholar
171. McCallum, S., Clowes, P. and Welch, A. (2005) A four-layer attenuation compensated PET detector based on APD arrays without discrete crystal elements. Physics in Medicine and Biology 50, 4187-4207 Google Scholar
172. Maramraju, S.H. et al. (2011) Small animal simultaneous PET/MRI: initial experiences in a 9.4T microMRI. Physics in Medicine and Biology 56, 2459-2480 Google Scholar
173. Yoon, H.S. et al. (2012) Initial results of simultaneous PET/MRI experiments with an MRI-compatible silicon photomultiplier PET scanner. Journal of Nuclear Medicine 53, 608-614 Google Scholar
174. Rischpler, C. et al. (2015) PET/MRI early after myocardial infarction: evaluation of viability with late gadolinium enhancement transmurality vs. 18F-FDG uptake. European Heart Journal Cardiovascular Imaging 16, 661-669 Google Scholar
175. Schwenzer, N.F. et al. (2012) Pulmonary lesion assessment: comparison of whole-body hybrid MR/PET and PET/CT imaging – pilot study. Radiology 264, 551-558 Google Scholar
176. Rauscher, I. et al. (2014) PET/MR imaging in the detection and characterization of pulmonary lesions: technical and diagnostic evaluation in comparison to PET/CT. Journal of Nuclear Medicine 55, 724-729 Google Scholar
177. Paulus, D.H., Tellmann, L. and Quick, H.H. (2013) Towards improved hardware component attenuation correction in PET/MR hybrid imaging. Physics in Medicine and Biology 58, 8021-8040 Google Scholar
178. Mollet, P. et al. (2014) Improvement of attenuation correction in time-of-flight PET/MR imaging with a positron-emitting source. Journal of Nuclear Medicine 55, 329-336 Google Scholar
179. Ripa, R.S. et al. (2013) Feasibility of simultaneous PET/MR of the carotid artery: first clinical experience and comparison to PET/CT. American Journal of Nuclear Medicine and Molecular Imaging 3, 361-371 Google Scholar
180. Uppal, R. et al. (2011) Bimodal thrombus imaging: simultaneous PET/MR imaging with a fibrin-targeted dual PET/MR probe – feasibility study in rat model. Radiology 258, 812-820 Google Scholar
181. Kawachi, E. et al. (2013) Novel molecular imaging of atherosclerosis with gallium-68-labeled apolipoprotein A-I mimetic peptide and positron emission tomography. Circulation Journal 77, 1482-1489 Google Scholar
182. Langer, H.F. (2008) Radionuclide imaging: a molecular key to the atherosclerotic plaque. Journal of the American College of Cardiology 52, 1-12 Google Scholar
183. Pietzsch, J. et al. (2005) Catabolism of native and oxidized low density lipoproteins: in vivo insights from small animal positron emission tomography studies. Amino Acids 29, 389-404 Google Scholar