Although standard MRI techniques provide valuable structural insight, a related technique known as magnetic resonance spectroscopy (MRS) adds powerful real-time metabolic information about the tissues under study. MRS provides early detection of disease, monitoring treatment efficacy, and, in the case of cancer, a dramatic reduction in unnecessary biopsies. However, broad utilization of MRS in the clinic is hindered by the low sensitivity of the underlying nuclear magnetic resonance phenomenon. Dynamic nuclear polarization (DNP) dramatically enhances nuclear magnetic resonance signals by transferring polarization from relatively highly-polarized unpaired-electron spins to nuclear spins (e.g. 1H, 13C, 19F, 23Na, 31P). The unpaired electrons are supplied by polarizing agents, which are persistent radical species added to a glass-forming matrix. Signal-to-noise ratio (SNR) improvements of over 10,000-fold are achievable with DNP. Hyperpolarized contrast agents and the high sensitivity afforded by DNP, combine to make MR-based imaging a safe and highly flexible diagnostic method. The recent availability of commercial polarizers has now made DNP-MRS accessible to research groups and medical centers. These advances are highlighted by the very promising studies, including a successful phase I clinical trial, of our collaborators at the University of California, San Francisco (UCSF). Remarkably, most endogenous compounds can be hyperpolarized and have the potential to be used as MRS probes, thereby replacing potentially toxic gadolinium (Gd) contrast agents. Successful MRS probes (contrast agents) for hyperpolarization must have several features including solubility in the selected solution, compatibility with the formation of a molecular glass, display a sufficiently long polarization lifetime (T1), and provide for facile separation from the polarization agent. Each probe requires its own set of polarization conditions, and as a result a library of polarization agents is necessary. Currently DNP-MRS probes are polarized with limited efficiency using only a couple different synthetically onerous and costly trityl-type radicals. Recently, DyNuPol's co-founders developed at MIT a superior polarization-agent technology based on 1,3-bisdiphenylene-2-phenylallyl (BDPA), which is licensed by DyNuPol. The modular nature of these compounds allows for tuning of the solubility through the rapid generation of a variety of derivatives that can be matched to numerous endogenous probes. In this Phase I effort we propose the application of our BDPA technology for the production of tunable polarization agents to expand the applicability of DNP-MRS. If successful, these proposed radicals and methods will generate immediate sales and allow high fidelity testing of a wide range of probes thereby enabling powerful new tools for the medical imaging community.
A technique known as dynamic nuclear polarization (DNP) offers the promise to increase the sensitivity of magnetic resonance spectroscopy (MRS) by e104, thus addressing its major shortcoming. By increasing the sensitivity of MRS, our proposed radicals can dramatically accelerate the understanding of a large number of diseases and metabolic disorders. This project will tailor the properties of the polarization agents used in thi technique thus enabling the study of a wider variety of diseases.