The nuclear magnetic resonance (NMR) spectrometer has allowed for the rapid characterization of reaction products, structural determination of chemical and biological materials, monitoring of reactions in progress and the non- invasive visualization of the inside of a living human body. Despite its utility, NMR and its medicinal counterpart (magnetic resonance imaging, MRI) are intrinsically limited by low sensitivity.1, 2 Tethered biradicals with a fixed relative orientation are known to increase the signal intensity of NMR spectra via dynamic nuclear polarization (DNP). 3-6 With the success of conformationally rigid small molecule biradicals as our cue, the goal of this proposal is to synthesize polymer-based DNP agents with controlled orientation. Goal 1: Polymeric DNP materials will be made for use in the contemporary, solid state DNP experiment and will provide the benefit of easy separation from substrate post NMR experiment. The challenge is incorporating stable radicals into a rigid backbone or fixing pre-tethered systems. Goal 2: Stationary phase, multi-radical species will also be explored as bulk polarization substrates for enhancement of molecules prior to introduction to MRI or NMR spectrometers. Such materials will require the incorporation of many radicals into a single moiety and, under the proper conditions, allow for the orientation of the biradicals with respect to each other7 and the external field. Insoluble polymers, polymers conjugated to a surface or stimuli-responsive polymers will be explored for bulk polarization. Goal 3: The conjugation of a molecular transporter to a biradical could be used for DNP enhancement of whole, living cells. This system will require a non-toxic polarization agent or a transporter that can remain polarized for long periods of time,8, 9 and it will allow for transport and targeting strategies10-12 that may be used for general or selective DNP enhancement in vivo. The proposed research has the potential to improve upon the success of MRI and significantly advance our ability to protect human health by the more expedient and earlier diagnosis of disease empowered by the improved sensitivity of DNP-MRI.

Public Health Relevance

The magnetic resonance imaging (MRI) machine is arguably the most important medical instrument of the last century, but, despite its utility, MRI is intrinsically limited by low sensitivity.1 Polymeric polarization materials could increase the sensitivity of MRI several thousand times2-4 and provide a means of selectively enhancing the signal from specific (i.e. cancerous) tissues5-7 all without introducing toxic materials into the body. This research project has the potential to improve upon the success story of MRI and to significantly advance our ability to protect human health by the more expedient and earlier diagnosis of disease empowered by the improved sensitivity of polarization- assisted MRI.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F04A-B (20))
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Erim, Zeynep
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Massachusetts Institute of Technology
Schools of Arts and Sciences
United States
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Kiesewetter, Matthew K; Michaelis, Vladimir K; Walish, Joseph J et al. (2014) High field dynamic nuclear polarization NMR with surfactant sheltered biradicals. J Phys Chem B 118:1825-30
Kiesewetter, Matthew K; Corzilius, Bjorn; Smith, Albert A et al. (2012) Dynamic nuclear polarization with a water-soluble rigid biradical. J Am Chem Soc 134:4537-40