Skip to main content
Top
Published in: Basic Research in Cardiology 2/2008

01-03-2008 | REVIEW

Contrast agents for MRI

Authors: Emily A. Waters, Samuel A. Wickline

Published in: Basic Research in Cardiology | Issue 2/2008

Login to get access

Abstract

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.
Literature
1.
go back to reference 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 115:377–386PubMedCrossRef 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 115:377–386PubMedCrossRef
2.
go back to reference 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 104:961–966PubMedCrossRef 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 104:961–966PubMedCrossRef
3.
go back to reference 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 76:1123–1130PubMedCrossRef 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 76:1123–1130PubMedCrossRef
4.
go back to reference 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 109:2023–2029PubMedCrossRef 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 109:2023–2029PubMedCrossRef
5.
go back to reference 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 7:861–867PubMedCrossRef 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 7:861–867PubMedCrossRef
6.
go back to reference 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 104:1280–1285PubMedCrossRef 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 104:1280–1285PubMedCrossRef
7.
go back to reference 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 228:480–487PubMedCrossRef 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 228:480–487PubMedCrossRef
8.
go back to reference 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 5:551–566PubMedCrossRef 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 5:551–566PubMedCrossRef
9.
go back to reference 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 115:2292–2298PubMedCrossRef 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 115:2292–2298PubMedCrossRef
10.
go back to reference 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 106:1195–1198PubMedCrossRef 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 106:1195–1198PubMedCrossRef
11.
go back to reference 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 107:2453–2458PubMedCrossRef 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 107:2453–2458PubMedCrossRef
12.
go back to reference 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 107:2290–2293PubMedCrossRef 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 107:2290–2293PubMedCrossRef
13.
go back to reference 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 94:3334–3340PubMed 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 94:3334–3340PubMed
14.
go back to reference 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 106:2842–2847PubMedCrossRef 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 106:2842–2847PubMedCrossRef
15.
go back to reference 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 55:126–135PubMedCrossRef 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 55:126–135PubMedCrossRef
16.
go back to reference 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 307:538–544PubMedCrossRef 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 307:538–544PubMedCrossRef
17.
go back to reference 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 52:1255–1262PubMedCrossRef 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 52:1255–1262PubMedCrossRef
18.
go back to reference 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 99:1726–1732PubMed 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 99:1726–1732PubMed
19.
go back to reference 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 6:1–6PubMedCrossRef 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 6:1–6PubMedCrossRef
20.
go back to reference 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 15:799–806PubMedCrossRef 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 15:799–806PubMedCrossRef
21.
go back to reference 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 21:1647–1654PubMedCrossRef 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 21:1647–1654PubMedCrossRef
22.
go back to reference 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 40:648–654PubMedCrossRef 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 40:648–654PubMedCrossRef
23.
go back to reference 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 103:415–422PubMed 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 103:415–422PubMed
24.
go back to reference Schellenberger EA, Hogemann D, Josephson L, Weissleder R (2002) Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI. Acad Radiol 9:S310–S311PubMedCrossRef Schellenberger EA, Hogemann D, Josephson L, Weissleder R (2002) Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI. Acad Radiol 9:S310–S311PubMedCrossRef
25.
go back to reference 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 3915–3917 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 3915–3917
26.
go back to reference 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 115:1384–1391PubMedCrossRef 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 115:1384–1391PubMedCrossRef
27.
go back to reference 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 112:396–399PubMedCrossRef 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 112:396–399PubMedCrossRef
28.
go back to reference 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 172:494–500PubMedCrossRef 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 172:494–500PubMedCrossRef
29.
go back to reference 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 25:2054–2061CrossRef 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 25:2054–2061CrossRef
30.
go back to reference 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 56:1384–1388PubMedCrossRef 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 56:1384–1388PubMedCrossRef
31.
go back to reference 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 108:2270–2274PubMedCrossRef 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 108:2270–2274PubMedCrossRef
32.
go back to reference 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 26:2103–2109CrossRef 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 26:2103–2109CrossRef
33.
go back to reference Wu J, Lee A, Lu YH, Lee RJ (2007) Vascular targeting of doxorubicin using cationic liposomes. Int J Pharm 337:329–335PubMedCrossRef Wu J, Lee A, Lu YH, Lee RJ (2007) Vascular targeting of doxorubicin using cationic liposomes. Int J Pharm 337:329–335PubMedCrossRef
Metadata
Title
Contrast agents for MRI
Authors
Emily A. Waters
Samuel A. Wickline
Publication date
01-03-2008
Publisher
D. Steinkopff-Verlag
Published in
Basic Research in Cardiology / Issue 2/2008
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI
https://doi.org/10.1007/s00395-008-0711-6

Other articles of this Issue 2/2008

Basic Research in Cardiology 2/2008 Go to the issue