Basic Research in Cardiology

, Volume 103, Issue 2, pp 114–121 | Cite as

Contrast agents for MRI

  • Emily A. Waters
  • Samuel A. Wickline


Molecular imaging is a rapidly growing field with the potential to revolutionize cardiovascular medicine by shifting diagnostic focus from functional abnormalities which occur late in a disease process to the biochemical events which precipitate the earliest stages of disease. MRI is a modality well suited to this task as it allows a variety of contrast mechanisms for detection of epitopes of interest, as well as high-resolution anatomical localization and functional information. In this review, we discuss the widerange of available molecular MRI contrast agents and their application to diseases such as atherosclerosis, thrombus imaging, and stem cell tracking, along with opportunities for molecularly targeted drug delivery.

Key words

molecular imaging nanoparticles therapy MRI 


Conflict of Interest

E.A. Waters has no conflict of interest to declare. S.A. Wickline has a research agreement with Philips Medical Systems, he holds equity and is consultant of Kereos, Inc., and co-founder of PixelEXX System, Inc.


  1. 1.
    Aikawa E, Nahrendorf M, Sosnovik D, Lok VM, Jaffer FA, Aikawa M, Weissleder R (2007) Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation 115:377–386PubMedCrossRefGoogle Scholar
  2. 2.
    Amirbekian V, Lipinski MJ, Briley-Saebo KC, Amirbekian S, Aguinaldo JGS, Weinreb DB, Vucic E, Frias JC, Hyafil F, Mani V, Fisher EA, Fayad ZA (2007) Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. Proc Natl Acad Sci USA 104:961–966PubMedCrossRefGoogle Scholar
  3. 3.
    Arbab AS, Bashaw LA, Miller BR, Jordan EK, Bulte JWM, Frank JA (2003) Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonnance imaging after cell transplantation: methods and techniques. Transplantation 76:1123–1130PubMedCrossRefGoogle Scholar
  4. 4.
    Botnar RM, Perez AS, Witte S, Wiethoff AJ, Laredo J, Hamilton J, Quist W, Parsons EC, Vaidya A, Kolodziej A, Barrett JA, Graham PB, Weisskoff RM, Manning WJ, Johnstone MT (2004) In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent. Circulation 109:2023–2029PubMedCrossRefGoogle Scholar
  5. 5.
    Choi JH, Nguyen FT, Barone PW, Heller DA, Moll AE, Patel D, Boppart SA, Strano MS (2007) Multimodal biomedical imaging with asymmetric single-walled carbon nanotube/iron oxide nanoparticle complexes. Nano Lett 7:861–867PubMedCrossRefGoogle Scholar
  6. 6.
    Flacke S, Fischer S, Scott MJ, Fuhrhop RJ, Allen JS, McLean M, Winter P, Sicard GA, Gaffney PJ, Wickline SA, Lanza GM (2001) Novel MRI contrast agent for molecular imaging of fibrin implications for detecting vulnerable plaques. Circulation 104:1280–1285PubMedCrossRefGoogle Scholar
  7. 7.
    Frank JA, Miller BR, Arbab AS, Zywicke HA, Jordan EK, Lewis BK, Bryant LH, Bulte JWM (2003) Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology 228:480–487PubMedCrossRefGoogle Scholar
  8. 8.
    Ho C, Hitchens TK (2004) A non-invasive approach to detecting organ rejection by MRI: Monitoring the accumulation of immune cells at the transplanted organ. Curr Pharm Biotechnol 5:551–566PubMedCrossRefGoogle Scholar
  9. 9.
    Jaffer FA, Kim DE, Quinti L, Tung CH, Aikawa E, Pande AN, Kohler RH, Shi GP, Libby P, Weissleder R (2007) Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease-activatable fluorescence sensor. Circulation 115:2292–2298PubMedCrossRefGoogle Scholar
  10. 10.
    Kolodgie FD, John M, Khurana C, Farb A, Wilson PS, Acampado E, Desai N, Soon-Shiong P, Virmani R (2002) Sustained reduction of in-stent neointimal growth with the use of a novel systemic nanoparticle paclitaxel. Circulation 106:1195–1198PubMedCrossRefGoogle Scholar
  11. 11.
    Kooi ME, Cappendijk VC, Cleutjens KBJM, Kessels AGH, Kitslaar PJEH, Borgers M, Frederik PM, Daemen MJAP, van Engelshoven JMA (2003) Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation 107:2453–2458PubMedCrossRefGoogle Scholar
  12. 12.
    Kraitchman DL, Heldman AW, Atalar E, Amado LC, Martin BJ, Pittenger MF, Hare JM, Bulte JWM (2003) In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 107:2290–2293PubMedCrossRefGoogle Scholar
  13. 13.
    Lanza GM, Wallace KD, Scott MJ, Cacheris WP, Abendschein DR, Christy DH, Sharkey AM, Miller JG, Gaffney PJ, Wickline SA (1996) A novel site-targeted ultrasonic contrast agent with broad biomedical application. Circulation 94:3334–3340PubMedGoogle Scholar
  14. 14.
    Lanza GM, Yu X, Winter PM, Abendschein DR, Karukstis KK, Scott MJ, Chinen LK, Fuhrhop RW, Scherrer DE, Wickline SA (2002) Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent implications for rational therapy of restenosis. Circulation 106:2842–2847PubMedCrossRefGoogle Scholar
  15. 15.
    Mani V, Briley-Saebo KC, Itskovich VV, Samber DD, Fayad ZA (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 55:126–135PubMedCrossRefGoogle Scholar
  16. 16.
    Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307:538–544PubMedCrossRefGoogle Scholar
  17. 17.
    Morawski AM, Winter PM, Yu X, Fuhrhop RW, Scott MJ, Hockett F, Robertson JD, Gaffney PJ, Lanza GM, Wickline SA (2004) Quantitative “magnetic resonance immunohistochemistry” with ligand-targeted F-19 nanoparticles. Magn Reson Med 52:1255–1262PubMedCrossRefGoogle Scholar
  18. 18.
    Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J (1999) Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 99:1726–1732PubMedGoogle Scholar
  19. 19.
    Mulder WJM, Koole R, Brandwijk RJ, Storm G, Chin PTK, Strijkers GJ, Donega CD, Nicolay K, Griffioen AW (2006) Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Lett 6:1–6PubMedCrossRefGoogle Scholar
  20. 20.
    Mulder WJM, Strijkers GJ, Griffioen AW, van Bloois L, Molema G, Storm G, Koning GA, Nicolay K (2004) A liposomal system for contrast-enhanced magnetic resonance imaging of molecular targets. Bioconjug Chem 15:799–806PubMedCrossRefGoogle Scholar
  21. 21.
    Partlow KC, Chen JJ, Brant JA, Neubauer AM, Meyerrose TE, Creer MH, Nolta JA, Caruthers SD, Lanza GM, Wickline SA (2007) F-19 magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. Faseb J 21:1647–1654PubMedCrossRefGoogle Scholar
  22. 22.
    Penno E, Johnsson C, Johansson L, Ahlstrom H (2005) Comparison of ultrasmall superparamagnetic iron oxide particles and low molecular weight contrast agents to detect rejecting transplanted hearts with magnetic resonance imaging. Invest Radiol 40:648–654PubMedCrossRefGoogle Scholar
  23. 23.
    Ruehm SG, Corot C, Vogt P, Kolb S, Debatin JF (2001) Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits. Circulation 103:415–422PubMedGoogle Scholar
  24. 24.
    Schellenberger EA, Hogemann D, Josephson L, Weissleder R (2002) Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI. Acad Radiol 9:S310–S311PubMedCrossRefGoogle Scholar
  25. 25.
    Sitharaman B, Kissell KR, Hartman KB, Tran LA, Baikalov A, Rusakova I, Sun Y, Khant HA, Ludtke SJ, Chiu W, Laus S, Toth E, Helm L, Merbach AE, Wilson LJ (2005) Superparamagnetic gadonanotubes are high-performance MRI contrast agents. Chem Commun 3915–3917Google Scholar
  26. 26.
    Sosnovik DE, Nahrendorf M, Deliolanis N, Novikov M, Aikawa E, Josephson L, Rosenzweig A, Weissleder R, Ntziachristos V (2007) Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo. Circulation 115:1384–1391PubMedCrossRefGoogle Scholar
  27. 27.
    Spuentrup E, Fausten B, Kinzel S, Wiethoff AJ, Botnar RM, Graham PB, Haller S, Katoh M, Parsons EC, Manning WJ, Busch T, Gunther RW, Buecker A (2005) Molecular magnetic resonance imaging of atrial clots in a swine model. Circulation 112:396–399PubMedCrossRefGoogle Scholar
  28. 28.
    Spuentrup E, Katoh M, Wiethoff AJ, Parsons EC, Botnar RM, Mahnken AH, Gunther RW, Buecker A (2005) Molecular magnetic resonance imaging of pulmonary emboli with a fibrin-specific contrast agent. Am J Respir Crit Care Med 172:494–500PubMedCrossRefGoogle Scholar
  29. 29.
    Virmani R, Kolodgie FD, Burke AP, Finn AV, Gold HK, Tulenko TN, Wrenn SP, Narula J (2005) Atherosclerotic plaque progression and vulnerability to rupture - Angiogenesis as a source of intraplaque hemorrhage. Arterioscle Thromb Vasc Biol 25:2054–2061CrossRefGoogle Scholar
  30. 30.
    Winter PM, Cai KJ, Chen J, Adair CR, Kiefer GE, Athey PS, Gaffney PJ, Buff CE, Robertson JD, Caruthers SD, Wickline SA, Lanza GM (2006) Targeted PARACEST nanoparticle contrast agent for the detection of fibrin. Magn Reson Med 56:1384–1388PubMedCrossRefGoogle Scholar
  31. 31.
    Winter PM, Morawski AM, Caruthers SD, Fuhrhop RW, Zhang HY, Williams TA, Allen JS, Lacy EK, Robertson JD, Lanza GM, Wickline SA (2003) Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta(3)-integrin-targeted nanoparticles. Circulation 108:2270–2274PubMedCrossRefGoogle Scholar
  32. 32.
    Winter PM, Neubauer AM, Caruthers SD, Harris TD, Robertson JD, Williams TA, Schmieder AH, Hu G, Allen JS, Lacy EK, Zhang HY, Wickline SA, Lanza GM (2006) Endothelial alpha(v)beta(3) integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arterioscle Thromb Vasc Biol 26:2103–2109CrossRefGoogle Scholar
  33. 33.
    Wu J, Lee A, Lu YH, Lee RJ (2007) Vascular targeting of doxorubicin using cationic liposomes. Int J Pharm 337:329–335PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  1. 1.Dept. of CardiologyWashington University Medical SchoolSaint LouisUSA

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