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Because of the demand for an extension of the range of diagnostic uses for currently available extracellular magnetic resonance imaging (MRI) contrast agents, a new generation of tissue-specific (i.e., hepatobiliary) contrast agents have been successfully developed to enhance the performance of hepatic MRI. These agents include mangafodipir trisodium (formerly manganese dipyridoxal diphosphate [Mn-DPDP]), gadoxetic acid (formerly gadolinium ethoxybenzyl diethylenetriaminopentaacetic acid [Gd-EOB-DTPA]), and gadolinium butylbenzyl diethylenetriaminepentaacetic acid (MS-264). In a series of experiments in animals, the potential of these agents for noninvasive characterization of liver lesions was evaluated with the use of a comprehensive methodology. The purpose of this report was to summarize the observed imaging behaviors of these agents toward different types of cholestasis and focal liver lesions, compare the similarities or dissimilarities of these agents in their possible mechanisms of action, and discuss the clinical implications of the results of the experiments. In summary, through intravenous administration of these agents, both global and local obstructive cholestases can be identified on the postcontrast image. With certain reliability, liver tumors of different origins and grades of cellular differentiation can be detected and classified according to their contrast enhancement patterns occurring at certain postcontrast phases. The invasiveness or degree of malignancy of the liver tumor can also be suggested by the presence or absence of a peritumoral rim sign. Such diagnostic information, otherwise only invasively achievable, may prove to be invaluable in clinical decision making.