Molecular Imaging in Cardiovascular Magnetic Resonance Imaging

Abstract

The development of novel imaging agents and techniques is allowing some biological events to be imaged in vivo with magnetic resonance imaging (MRI) at the cellular and subcellular level. In this paper, the use of novel gadolinium chelates and superparamagnetic iron oxide nanoparticles for molecular MRI of the cardiovascular system is extensively reviewed. The physical properties of these imaging agents and the pulse sequences best suited to their visualization are extensively discussed. The application of molecular MRI in diseases of the vasculature and myocardium is then reviewed. The clinical experience to date, as well as the promise and potential impact of molecular MRI, is extensively discussed.Keywords magnetic resonance imaging; molecular imaging; cardiovascular; iron oxide; nanoparticles; myocardium; atherosclerosis Molecular magnetic resonance imaging (MRI) refers to the noninvasive imaging of events at the cellular and subcellular level with MRI in vivo. Although the experience to date with nuclear-based molecular imaging techniques is greater, the advantages of an MRI-based approach to cardiovascular imaging include its high spatial resolution, excellent soft tissue contrast, and ability to simultaneously image cardiovascular anatomy, physiology, and molecular events. 1 Molecular MRI is already playing an important role in preclinical investigation and has the potential to play a major role in the clinical arena in the near future. 1 The present paper focuses on the role of MRI in cardiovascular molecular imaging, and the interested reader is referred to several broad reviews of the field for a more detailed discussion of other molecular imaging modalities as well. 1-3 MOLECULAR MRI AGENTSThe principal challenge of molecular MRI, in comparison with other molecular imaging techniques such as single photon emission computed tomography/positron emission tomography (PET) and fluorescence, lies in its lower sensitivity. Conventional gadolinium chelates have a sensitivity in the micromolar range, which is significantly better than iodinated contrast agents (millimolar range) but significantly worse than radiotracer and fluorescence techniques (picomolar or better). 1,3,4 Two approaches have been developed to deal with this problem. The first involves the selection of highly expressed molecular targets, such as fibrin in thrombi or type 1 collagen in areas of fibrosis. 5,6 Because these targets are so abundant, NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript small gadolinium chelates with relatively low relaxivity values can be used for their detection. These agents are also similar in size to clinically approved gadolinium chelates, simplifying some aspects of their pharmacokinetic and toxicological evaluation. The principal disadvantage of this approach, however, lies in its low sensitivity per binding event (low level of signal generated for each unit ligand that binds to the target). This limits the applicability of this approach to highly expressed targets and also re...

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