IRFP: Novel MRI Methods for Hyperpolarized Biomolecular Systems

国际研究奖学金计划使美国科学家和工程师能够在国外进行9到24个月的研究。该计划的奖项提供了联合研究的机会，以及利用国外独特或互补的设施、专业知识和实验条件的机会。该奖项将支持Avidor Leftin博士与以色列魏茨曼科学研究所的Lucio Frydman博士合作，为期24个月的研究奖学金。该奖项将为实时、动态核极化(DNP)辅助磁共振光谱成像(MRSI)方法的开发领域做出贡献，为该项目分享我在生物物理系统结构动力学的核磁共振光谱领域的经验，并促进以色列-美国科学界之间的合作。磁共振领域的一项革命性突破是魏兹曼科学研究所的Frydman小组所追求的超快、空间编码的核磁共振(核磁共振)方法的出现。这项技术结合了多维(ND)核磁共振波谱和核磁共振成像的原理，将测量时间从数小时减少到毫秒。此外，该小组还成功地展示了应用非原位动态核极化(DNP)的优势，DNP正迅速成为核磁共振和核磁共振成像研究中不可或缺的组成部分，与这些节省时间的核磁共振实验相结合，超极化系统的信噪比接近热极化样品的103至106倍。目标是将ND生物分子核磁共振波谱的各个方面与新的ND MRSI协议结合起来，所有这些都是用DNP完成的。这些混合的、DNP辅助的MRSI协议将针对一组选定的生物分子物种，这些生物分子物种将用于展示真正的单次扫描、空间定位的ND光谱数据监测。这种使用DNP的ND生物分子核磁共振和MRSI的融合有望通过研究经验和技术进步的融合将不同的科学观点结合在一起。在博士后任命期间形成的创新和合作将使在超极化条件下实现空间局部化多维(ND)光谱数据的真正单次扫描采集成为可能。在此期间发展的基本物理原理和所学到的技术熟练程度将继续推动魏茨曼研究所处于国际磁共振领域前沿的磁共振(MR)研究，并将在同行评议文章和国际研究会议上传播。特制的超快、超极化光谱成像方法(MRSI)的各种应用可能是为了阐明外源和内源分子靶标的结构、动力学和动力学变化，有助于我们理解体外和体内相互作用系统。这些混合磁共振方法将在基于MRSI的研究和生物分子核磁共振波谱方面带来迄今尚未开发的研究机会，并可能定义分子生物化学、生物物理学和新兴生物工程学科的一个新的研究模式领域。

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.