IRFP: Novel MRI Methods for Hyperpolarized Biomolecular Systems

Leftin, Avigdor, Tucson AZ

Investigators

Abstract

The International Research Fellowship Program enables U.S. scientists and engineers to conduct nine to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad. This award will support a twenty-four-month research fellowship by Dr. Avigdor Leftin to work with Dr. Lucio Frydman at the Weizmann Institute of Science, Israel. This award will contribute to the developing field of real-time, dynamic nuclear polarization (DNP) assisted magnetic resonance spectroscopic imaging (MRSI) methods, share into this project my own experience in the area of NMR spectroscopy of the structural dynamics of biophysical systems, and forge collaborations between the Israeli-American scientific communities. A revolutionary breakthrough in the field of magnetic resonance is the advent of ultrafast, spatially-encoded, nuclear magnetic resonance (NMR) methods pursued by the Frydman group at the Weizmann Institute of Science. This technique combines principles of multidimensional (nD) NMR spectroscopy and MRSI, reducing measuring times from hours to milliseconds. Further, this group has successfully demonstrated the advantage of applying ex situ dynamic nuclear polarization (DNP), which is quickly becoming an indispensible component of NMR and MRSI investigations, in conjunction with these time-saving NMR experiments to achieve signal-to-noise figures of hyperpolarized systems approaching 103 to 106 fold over thermally polarized samples. The goal is to incorporate aspects of nD biomolecular NMR spectroscopy with novel nD MRSI protocols, all done with DNP. These hybrid, DNP assisted MRSI protocols will target a selected group of biomolecular species that will be used to demonstrate true single-scan, spatially-localized monitoring of nD-spectral data. This fusion of nD biomolecular NMR and MRSI using DNP promises to bring together diverse scientific perspectives through a confluence of research experiences and technological advancements. The innovations and collaborations forged during the postdoctoral appointment will enable the realization of true single-scan acquisition of spatially localized multidimensional (nD) spectroscopic data under hyperpolarized conditions. The fundamental physical principles developed during this time, and the technical proficiency learned will continue to advance magnetic resonance (MR) research at the Weizmann Institute, at the forefront of the international magnetic resonance community, and will be disseminated in peer-reviewed articles and international research conferences. The various applications of the tailored ultrafast, hyperpolarized spectroscopic imaging methods (MRSI) may be targeted for the elucidation of structural, dynamic, and kinetic transformations of exogenous and endogenous molecular targets contributing to our understanding of both in vitro and in vivo interaction systems. These hybrid magnetic resonance methods will lead to hitherto untapped research opportunities in both MRSI based investigations and biomolecular NMR spectroscopy and will potentially define a new field of research modalities in molecular biochemistry, biophysics, and emerging bioengineering disciplines.