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Abstract
Tens of millions of contrast-enhanced magnetic resonance imaging (MRI) exams are performed
annually around the world. The contrast agents, which improve diagnostic accuracy,
are almost exclusively small, hydrophilic gadolinium(III) based chelates. In recent
years concerns have arisen surrounding the long-term safety of these compounds, and
this has spurred research into alternatives. There has also been a push to develop
new molecularly targeted contrast agents or agents that can sense pathological changes
in the local environment. This comprehensive review describes the state of the art
of clinically approved contrast agents, their mechanism of action, and factors influencing
their safety. From there we describe different mechanisms of generating MR image contrast
such as relaxation, chemical exchange saturation transfer, and direct detection and
the types of molecules that are effective for these purposes. Next we describe efforts
to make safer contrast agents either by increasing relaxivity, increasing resistance
to metal ion release, or by moving to gadolinium(III)-free alternatives. Finally we
survey approaches to make contrast agents more specific for pathology either by direct
biochemical targeting or by the design of responsive or activatable contrast agents.
[1
]Athinoula A. Martinos Center for Biomedical Imaging and the Institute for Innovation
in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical
School, Charlestown, Massachusetts 02129, United States