Improving Understanding, Utility and Generality of Hyperpolarized, Long-lived Spin States in Magnetic Resonance

核磁共振（NMR）光谱是化学家的强大工具；它对确定分子结构和监测化学反应的进展是有用的。核磁共振的临床表亲，核磁共振成像（MRI）也是产生人体软组织图像的有用工具。这两种方法的灵敏度都相对较低，这意味着它们不能检测到少量的样品。“超极化”方法可以将信号增加1000倍或更多，在过去十年中得到了广泛的探索，但只有不到1%的核磁共振和核磁共振能够使用这种技术。超极化在技术上具有挑战性，而且极其昂贵。在化学测量和成像项目的支持下，以及化学结构、动力学和机制项目的部分共同资助下，杜克大学的Warren Warren、Steven Malcolmson和Thomas Theis教授及其团队正在努力扩大超极化（一种现成的试剂）的可用性和实用性。他们正在开发新的催化剂来加速样品制备，并开发一种仪器，其成本仅为竞争对手方法的1%左右。这项研究既扩大了可能的分子靶标范围，又提高了可达到的灵敏度。该项目最终可能实现低成本、便携式核磁共振成像仪器。该团队正在为代表性不足的群体成员提供这些关键技术的研究和培训机会，并提供大量的K-12科学外展。核磁共振和核磁共振的低灵敏度往往是一个严重的限制。超极化方法（主要是动态核极化，DNP）几乎可以在任何有机分子中增加10,000倍的可观测信号，但超极化以核自旋寿命T1给出的速率衰减回热平衡，这在溶液中通常是秒。这些短暂的弛豫时间限制了该方法可以研究的过程。此外，相关设备复杂且昂贵（临床系统约250万美元）。杜克大学的研究小组已经证明，脉冲序列可以在许多分子中加载和卸载长寿命状态，有效地将均匀弛豫时间延长到几分钟。他们的超极化新方法（SABRE-SHEATH和LIGHT-SABRE）使用本科生可以建造的超低场设备（约占地球场的1%），将15氮或13碳的极化提高了5个数量级（相对于热人口）。他们现在正在努力提高极化率、总极化率和这些方法的通用性。本研究项目的目的是降低对分子参数的敏感性，提高可靠性。这项工作包括发现、对磁共振密度矩阵理解的基本理论扩展、详细的量子力学和分子动力学模拟、目标合成和有用应用的演示。这项研究正在解决有关自旋动力学的基本问题。这些系统反映了一类新的“反应中间体”，它们会回到它们的原始状态，但会产生有用的产物（自旋极化核）。其他扩展集中于分子对称在将状态与其环境隔离方面的复杂作用，以及开发工具来访问更好的受保护状态。更广泛的影响来自于创造各种磁共振可追踪分子靶标的潜力，应用范围从有机金属化学到临床成像。

Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for chemists; it is useful for determining molecular structure and for monitoring the progress of chemical reactions. NMR's clinical cousin, magnetic resonance imaging (MRI) is also a useful tool for producing images of soft tissues in the body. Both methods usually suffer from relatively low sensitivity - meaning that it cannot detect small amounts of sample. "Hyperpolarization" methods, which can increase the signal by a factor of 1000 or more, have been extensively explored over the last decade, but fewer than 1% of all NMRs and MRIs have access to this technology. Hyperpolarization is technically challenging and extremely expensive. With support from the Chemical Measurement and Imaging Program, and partial co-funding from the Chemical Structure, Dynamics, and Mechanisms - A Program, Professors Warren Warren, Steven Malcolmson, and Thomas Theis and their groups at Duke University are working to expand the availability and utility of hyperpolarization (a readily prepared reagent). They are developing new catalysts to speed sample preparation and an instrument that can be built for about 1% of the cost of competitive approaches. This research is both expanding the range of possible molecular targets and increasing the attainable sensitivity. The project could ultimately enable low-cost, portable MRI instruments. The team is providing research and training opportunities in these critical technologies for members of underrepresented groups, and providing substantial K-12 science outreach.The low sensitivity of NMR and MRI is often a severe limitation. Hyperpolarization methods (mostly dynamic nuclear polarization, DNP) can increase the observable signal as much as 10,000 times in virtually any organic molecule, but hyperpolarization decays back to thermal equilibrium at a rate given by the nuclear spin lifetime T1, which in solution is commonly seconds. These short relaxation times limit the processes that can be studied by the method. In addition, the associated apparatus is complicated and expensive (ca. $2.5M for clinical systems). The team at Duke has shown that pulse sequences can load and unload long-lived states in many molecules, effectively lengthening homogeneous relaxation times to many minutes. Their new approaches to hyperpolarization (SABRE-SHEATH and LIGHT-SABRE) have increased 15Nitrogen or 13Carbon polarization by up to five orders of magnitude (relative to thermal populations) using an ultralow-field apparatus (about 1% of the Earth's field) that can be built by undergraduates. They are now working to improve polarization rates, total polarization, and the generality of these methods. The aim of this research project is to reduce the sensitivity to molecular parameters and increase reliability. The work includes a mixture of discovery, basic theoretical extensions of the density matrix understanding of magnetic resonance, detailed quantum mechanical and molecule dynamics simulations, targeted synthesis, and demonstration of useful applications. The research is addressing fundamental questions about spin dynamics. The systems reflect a new class of "reactive intermediates" which go back to their original state, yet create a useful product (spin polarized nuclei). Other extensions focus on the complex role of molecular symmetry in isolating states from their environment, and on developing tools to access ever-better protected states. Broader impacts arise from the potential to create a wide variety of Magnetic Resonance-trackable molecular targets, with applications from organometallic chemistry to clinical imaging.