Skip to main content
SpringerLink
Log in

Molecular MRI of atherosclerotic plaque with targeted contrast agents

  • Published:
Current Cardiovascular Imaging Reports Aims and scope Submit manuscript

Abstract

Molecular MRI of atherosclerosis involves the use of novel contrast agents to image cellular and molecular processes within atherosclerotic plaque. Agents to image plaque lipid content, inflammation, angiogenesis, and thrombosis have been developed and studied extensively in animal models of atherosclerosis and vascular injury. Selected agents have also been studied in humans, with highly promising initial results. In this brief review, recent advances as well as opportunities and challenges in the field are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Sosnovik DE, Nahrendorf M, Weissleder R: Molecular magnetic resonance imaging in cardiovascular medicine. Circulation 2007, 115:2076–2086.

    Article  PubMed  Google Scholar 

  2. Jaffer FA, Libby P, Weissleder R: Molecular and cellular imaging of atherosclerosis: emerging applications. J Am Coll Cardiol 2006, 47:1328–1338.

    Article  PubMed  CAS  Google Scholar 

  3. Nahrendorf M, Jaffer FA, Kelly KA, et al.: Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 2006, 114:1504–1511.

    Article  PubMed  CAS  Google Scholar 

  4. Briley-Saebo KC, Shaw PX, Mulder WJ, et al.: Targeted molecular probes for imaging atherosclerotic lesions with magnetic resonance using antibodies that recognize oxidation-specific epitopes. Circulation 2008, 117:3206–3215.

    Article  PubMed  CAS  Google Scholar 

  5. Korosoglou G, Weiss RG, Kedziorek DA, et al.: Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using “positive contrast” magnetic resonance imaging. J Am Coll Cardiol 2008, 52:483–491.

    Article  PubMed  CAS  Google Scholar 

  6. Winter PM, Morawski AM, Caruthers SD, et al.: Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles. Circulation 2003, 108:2270–2274.

    Article  PubMed  CAS  Google Scholar 

  7. Botnar RM, Perez AS, Witte S, et al.: In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent. Circulation 2004, 109:2023–2029.

    Article  PubMed  CAS  Google Scholar 

  8. Trivedi RA, U-King-Im JM, Graves MJ, et al.: In vivo detection of macrophages in human carotid atheroma: temporal dependence of ultrasmall superparamagnetic particles of iron oxide-enhanced MRI. Stroke 2004, 35:1631–1635.

    Article  PubMed  Google Scholar 

  9. Kooi ME, Cappendijk VC, Cleutjens KB, et al.: Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation 2003, 107:2453–2458.

    Article  PubMed  CAS  Google Scholar 

  10. Spuentrup E, Botnar RM, Wiethoff AJ, et al.: MR imaging of thrombi using EP-2104R, a fibrin-specific contrast agent: initial results in patients. Eur Radiol 2008, 18:1995–2005.

    Article  PubMed  Google Scholar 

  11. Flacke S, Fischer S, Scott MJ, et al.: Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques. Circulation 2001, 104:1280–1285.

    Article  PubMed  CAS  Google Scholar 

  12. Overoye-Chan K, Koerner S, Looby RJ, et al.: EP-2104R: a fibrin-specific gadolinium-based MRI contrast agent for detection of thrombus. J Am Chem Soc 2008, 130:6025–6039.

    Article  PubMed  CAS  Google Scholar 

  13. Chen JW, Pham W, Weissleder R, Bogdanov A Jr: Human myeloperoxidase: a potential target for molecular MR imaging in atherosclerosis. Magn Reson Med 2004, 52:1021–1028.

    Article  PubMed  CAS  Google Scholar 

  14. Lancelot E, Amirbekian V, Brigger I, et al.: Evaluation of matrix metalloproteinases in atherosclerosis using a novel noninvasive imaging approach. Arterioscler Thromb Vasc Biol 2008, 28:425–432.

    Article  PubMed  CAS  Google Scholar 

  15. Lipinski MJ, Amirbekian V, Frias JC, et al.: MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor. Magn Reson Med 2006, 56:601–610.

    Article  PubMed  Google Scholar 

  16. Amirbekian V, Lipinski MJ, Briley-Saebo KC, et al.: Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. Proc Natl Acad Sci U S A 2007, 104:961–966.

    Article  PubMed  CAS  Google Scholar 

  17. Mulder WJ, Strijkers GJ, Briley-Saboe KC, et al.: Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG-micelles. Magn Reson Med 2007, 58:1164–1170.

    Article  PubMed  Google Scholar 

  18. Li H, Gray BD, Corbin I, et al.: MR and fl uorescent imaging of low-density lipoprotein receptors. Acad Radiol 2004, 11:1251–1259.

    Article  PubMed  Google Scholar 

  19. Frias JC, Williams KJ, Fisher EA, Fayad ZA: Recombinant HDL-like nanoparticles: a specifi c contrast agent for MRI of atherosclerotic plaques. J Am Chem Soc 2004, 126:16316–16317.

    Article  PubMed  CAS  Google Scholar 

  20. Meding J, Urich M, Licha K, et al.: Magnetic resonance imaging of atherosclerosis by targeting extracellular matrix deposition with Gadofl uorine M. Contrast Media Mol Imaging 2007, 2:120–129.

    Article  PubMed  CAS  Google Scholar 

  21. Barkhausen J, Ebert W, Heyer C, et al.: Detection of atherosclerotic plaque with Gadofl uorine-enhanced magnetic resonance imaging. Circulation 2003, 108:605–609.

    Article  PubMed  CAS  Google Scholar 

  22. Yeon SB, Sabir A, Clouse M, et al.: Delayed-enhancement cardiovascular magnetic resonance coronary artery wall imaging: comparison with multislice computed tomography and quantitative coronary angiography. J Am Coll Cardiol 2007, 50:441–447.

    Article  PubMed  Google Scholar 

  23. Fuster V, Moreno PR, Fayad ZA, et al.: Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol 2005, 46:937–954.

    Article  PubMed  Google Scholar 

  24. Shah PK: Pathophysiology of coronary thrombosis: role of plaque rupture and plaque erosion. Prog Cardiovasc Dis 2002, 44:357–368.

    Article  PubMed  Google Scholar 

  25. Virmani R, Burke AP, Kolodgie FD, Farb A: Vulnerable plaque: the pathology of unstable coronary lesions. J Interv Cardiol 2002, 15:439–446.

    Article  PubMed  Google Scholar 

  26. Sirol M, Aguinaldo JG, Graham PB, et al.: Fibrin-targeted contrast agent for improvement of in vivo acute thrombus detection with magnetic resonance imaging. Atherosclerosis 2005, 182:79–85.

    Article  PubMed  CAS  Google Scholar 

  27. Botnar RM, Buecker A, Wiethoff AJ, et al.: In vivo magnetic resonance imaging of coronary thrombosis using a fibrin-binding molecular magnetic resonance contrast agent. Circulation 2004, 110:1463–1466.

    Article  PubMed  Google Scholar 

  28. Spuentrup E, Buecker A, Katoh M, et al.: Molecular magnetic resonance imaging of coronary thrombosis and pulmonary emboli with a novel fibrin-targeted contrast agent. Circulation 2005, 111:1377–1382.

    Article  PubMed  CAS  Google Scholar 

  29. Spuentrup E, Fausten B, Kinzel S, et al.: Molecular magnetic resonance imaging of atrial clots in a swine model. Circulation 2005, 112:396–399.

    Article  PubMed  Google Scholar 

  30. Spuentrup E, Katoh M, Wiethoff AJ, et al.: Molecular magnetic resonance imaging of pulmonary emboli with a fibrin-specific contrast agent. Am J Respir Crit Care Med 2005, 172:494–500.

    Article  PubMed  Google Scholar 

  31. Spuentrup E, Katoh M, Buecker A, et al.: Molecular MR imaging of human thrombi in a swine model of pulmonary embolism using a fibrin-specific contrast agent. Invest Radiol 2007, 42:586–595.

    Article  PubMed  CAS  Google Scholar 

  32. Sosnovik DE, Nahrendorf M, Weissleder R: Magnetic nanoparticles for MR imaging: agents, techniques and cardiovascular applications. Basic Res Cardiol 2008, 103:122–130.

    Article  PubMed  CAS  Google Scholar 

  33. McAteer MA, Schneider JE, Ali ZA, et al.: Magnetic resonance imaging of endothelial adhesion molecules in mouse atherosclerosis using dual-targeted microparticles of iron oxide. Arterioscler Thromb Vasc Biol 2008, 28:77–83.

    Article  PubMed  CAS  Google Scholar 

  34. von zur Muhlen C, von Elverfeldt D, Moeller JA, et al.: Magnetic resonance imaging contrast agent targeted toward activated platelets allows in vivo detection of thrombosis and monitoring of thrombolysis. Circulation 2008, 118:258–267.

    Article  Google Scholar 

  35. Jaffer FA, Nahrendorf M, Sosnovik D, et al.: Cellular imaging of inflammation in atherosclerosis using magneto-fluorescent nanomaterials. Mol Imaging 2006, 5:85–92.

    PubMed  Google Scholar 

  36. Weissleder R, Kelly K, Sun EY, et al.: Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol 2005, 23:1418–1423.

    Article  PubMed  CAS  Google Scholar 

  37. Sosnovik DE, Nahrendorf M, Deliolanis N, et al.: Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo. Circulation 2007, 115:1384–1391.

    Article  PubMed  Google Scholar 

  38. Sosnovik DE, Schellenberger EA, Nahrendorf M, et al.: Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto-optical nanoparticle. Magn Reson Med 2005, 54:718–724.

    Article  PubMed  Google Scholar 

  39. Stuber M, Gilson WD, Schar M, et al.: Positive contrast visualization of iron oxide-labeled stem cells using inversion-recovery with ON-resonant water suppression (IRON). Magn Reson Med 2007, 58:1072–1077.

    Article  PubMed  Google Scholar 

  40. Farrar CT, Dai G, Novikov M, et al.: Impact of field strength and iron oxide nanoparticle concentration on the linearity and diagnostic accuracy of off-resonance imaging. NMR Biomed 2008, 21:453–463.

    Article  PubMed  CAS  Google Scholar 

  41. Mani V, Briley-Saebo KC, Hyafil F, Fayad ZA: Feasibility of in vivo identification of endogenous ferritin with positive contrast MRI in rabbit carotid crush injury using GRASP. Magn Reson Med 2006, 56:1096–1106.

    Article  PubMed  CAS  Google Scholar 

  42. Harisinghani MG, Barentsz J, Hahn PF, et al.: Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003, 348:2491–2499.

    Article  PubMed  Google Scholar 

  43. Winter PM, Neubauer AM, Caruthers SD, et al.: Endothelial alpha(v)beta3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arterioscler Thromb Vasc Biol 2006, 26:2103–2109.

    Article  PubMed  CAS  Google Scholar 

  44. Nahrendorf M, Zhang H, Hembrador S, et al.: Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation 2008, 117:379–387.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Massachusetts General Hospital, 149 13th Street, Charlestown, MA, 02129, USA

    David E. Sosnovik

Authors
  1. David E. Sosnovik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Caravan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David E. Sosnovik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sosnovik, D.E., Caravan, P. Molecular MRI of atherosclerotic plaque with targeted contrast agents. curr cardiovasc imaging rep 2, 87–94 (2009). https://doi.org/10.1007/s12410-009-0012-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12410-009-0012-y

Keywords

Search

Navigation