Contrast agents: magnetic resonance

Even though the intrinsic magnetic resonance imaging (MRI) contrast is much more flexible than in other clinical imaging techniques, the diagnosis of several pathologies requires the involvement of contrast agents (CAs) that can enhance the difference between normal and diseased tissues by modifying their intrinsic parameters. MR CAs are indirect agents because they do not become visible by themselves as opposed to other imaging modalities. The signal enhancement produced by MRI CAs (i.e., the efficiency of the CAs) depends on their longitudinal (r1) and transverse (r2) relaxivity (expressed in s(-1) mmol(-1) 1), which is defined as the increase of the nuclear relaxation rate (the reciprocal of the relaxation time) of water protons produced by 1 mmol per liter of CA. Paramagnetic CAs (most of them complexes of gadolinium) are frequently used in clinics as extracellular, hepatobiliary or blood pool agents. Low molecular weight paramagnetic CAs have similar effects on R1 and R2, but the predominant effect at low doses is that of T1 shortening (and R1 enhancement). Thus, organs taking up such agents will become bright in a T1-weighted MRI sequence; these CAs are thus called positive contrast media. The CAs known as negative agents influence signal intensity mainly by shortening T2* and T2, which produces the darkening of the contrast-enhanced tissue. These CAs are generally composed of superparamagnetic nanoparticles, consisting of iron oxides (magnetite, Fe3O4, maghemite, gammaFe2O3, or other ferrites). Iron oxide nanoparticles are taken up by the monocyte-macrophage system, which explains their potential application as MRI markers of inflammatory and degenerative disorders. Most of the contemporary MRI CAs approved for clinical applications are non-specific for a particular pathology and report exclusively on the anatomy and the physiological status of various organs. A new generation of MRI CAs is progressively emerging in the current context of molecular imaging, agents that are designed to detect with a high specificity the cellular and molecular hallmarks of various pathologies.