Novel Hyperpolarization Approaches for Magnetic Resonance Applications

Duke University, Durham NC

Investigators

Abstract

With the support of the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Warren Warren at Duke University will develop methods which improve the utility and generality of nuclear magnetic resonance (NMR) spectroscopy. NMR is a powerful tool for chemists, physicists, and materials scientists, used for determining molecular structure and for monitoring the progress of chemical reactions. NMR's clinical cousin, magnetic resonance imaging (MRI) is an important tool for producing images of soft tissues in the body. However, both methods usually suffer from low sensitivity - meaning that they cannot detect small amounts of sample or low concentrations. "Hyperpolarization" methods can increase NMR signals by a factor of 10,000 or more, but are usually technically challenging and extremely expensive. This project will build on recent theoretical, computational, and experimental breakthroughs in the Warren lab that improve the performance of a simple, general and inexpensive hyperpolarization method (SABRE and its derivatives). For example, the Warren lab has recently demonstrated that shaped, multi-axis magnetic fields can improve polarization by nearly an order of magnitude over the established best approaches. The proposed research directions will reflect new insights that are expected to make this method the clear choice for most NMR applications, to broaden the uses of NMR in materials science, and to assist the creation of new portable, high-sensitivity MRI systems. The work will also provide research and training opportunities in these critical technologies as part of broad engagement activities for coworkers and continue to support substantial K-12 science outreach in the Durham public school system. The Warren group studies the production, quantum statistical mechanics, and characterization of hyperpolarized, long-lived nuclear spin states in NMR and MRI. SABRE methods can directly polarize nuclei such as 15N and 13C from para-hydrogen gas in solution (p-H2), using transient binding of a target ligand and p-H2 to an octahedral iridium complex to mediate spin transfer. In practice, the current performance of this very new method (the direct 15N polarization strategy was first published only a decade ago) slightly lags existing methods with fifty years of optimization, but it is at least a factor of 100 less expensive than those traditional approaches. The intellectual merit here comes from a set of new strategies to boost both generality and polarization levels. Some of these strategies are “tweaks” to the SABRE paradigm, such as new methods to improve ligand and hydrogen exchange. Some are a complete rethinking of the paradigm, possible now through the new and underexplored regime of large nuclear polarization coupled with extremely low fields that can be rapidly modulated or even inverted. All these strategies promise to increase polarization levels and increase general applicability. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.