Biomolecular MRI reporters: Evolution of new mechanisms
Magnetic resonance imaging (MRI) is a powerful technique for observing the function of specific cells and molecules inside living organisms. However, compared to optical microscopy, in which fluorescent protein reporters are available to visualize hundreds of cellular functions ranging from gene expression and chemical signaling to biomechanics, to date relatively few such reporters are available for MRI. Efforts to develop MRI-detectable biomolecules have mainly focused on proteins transporting paramagnetic metals for T_1 and T_2 relaxation enhancement or containing large numbers of exchangeable protons for chemical exchange saturation transfer. While these pioneering developments established several key uses of biomolecular MRI, such as imaging of gene expression and functional biosensing, they also revealed that low molecular sensitivity poses a major challenge for broader adoption in biology and medicine. Recently, new classes of biomolecular reporters have been developed based on alternative contrast mechanisms, including enhancement of spin diffusivity, interactions with hyperpolarized nuclei, and modulation of blood flow. These novel reporters promise to improve sensitivity and enable new forms of multiplexed and functional imaging.
© 2017 Elsevier B.V. Received 1 May 2017, Accepted 28 May 2017, Available online 3 June 2017. Work in the Shapiro laboratory related to this article is supported by the Heritage Medical Research Institute, the Burroughs Wellcome Career Award at the Scientific Interface, the Pew Scholarship in the Biomedical Sciences, the Packard Fellowship for Science and Engineering, the Dana Foundation, the Human Frontier Science Program, the W.M. Keck Foundation and the National Institutes of Health (U54CA199090A). AM was supported by the James G. Boswell Postdoctoral Fellowship. PR was supported by a NSF Graduate Research Fellowship and the NIH Biotechnology Leaders Program.
Accepted Version - nihms884907.pdf