Lighting up Magnetic Resonance: SABRE optimisation powered by in situ detection

磁共振成像（MRI）和核磁共振（NMR）光谱是从合成化学到医学诊断等应用的强大工具。然而，这些方法的缺点是灵敏度低。这意味着在被研究的样品中，每百万个原子核中只有几十个被实际检测到。例如，在标准NMR实验中检测到的1H核的分数对于所施加的每特斯拉磁场约为3.5ppm（百万分之一）。因此，只能研究相对大量的物质，并且需要昂贵的高磁场设备。一个有希望的途径，以显着改善磁共振是通过使用超极化。这是将检测到的核的分数增加到100，000倍的方法的名称。在这项工作中，我们专注于一种称为SABRE（可逆交换信号放大）的方法，该方法使用一种特殊形式的氢气，称为仲氢（p-H2），以产生超极化效应。SABRE使用过渡金属络合物将极化从p-H2气体催化转移到感兴趣的分子。这种方法有许多令人兴奋的应用。例如，在临床MRI中，超极化剂已经被注射到患者体内，然后被跟踪以获得关于功能和/或疾病的诊断信息。这只能通过超极化来实现，超极化允许相对少量的注射剂在体内所有其他分子的背景下被检测到。与其他方法相比，SABRE是一种相对较新的技术，因此对从p-H2到目标分子的极化转移过程的基本物理学知之甚少。许多理论模型已经提出，但他们的简化假设是很难实验测试。这是因为，在标准方法中，SABRE实验的检测阶段在时间和空间上与偏振阶段分离，使得直接询问转移过程具有挑战性。理解SABRE不仅是一项学术练习，而且也很重要。为了将SABRE转化为通用的超极化技术，需要一种有效的途径来优化新靶分子的极化。目前的经验优化方法是耗时的，昂贵的，并不能保证工作。这项工作的中心假设是，在现场进行的SABRE效应的直接测量-即在与极化转移发生的磁场条件相同的条件下-是为SABRE开发严格模型的最佳途径，从而实现合理和快速的优化。在这个项目中，我们将组装一个低场（1 - 20 mT）NMR仪器，可以用作直接研究SABRE核心极化转移过程的平台。这些实验结果将与理论见解相结合，以设计一个严格的模型，考虑到许多复杂的SABRE过程。这将导致极化转移优化的新策略，从而增加SABRE在医药和工业制造等领域的应用范围。

Magnetic resonance imaging (MRI) and nuclear magnetic resonance (NMR) spectroscopy are powerful tools for applications that range from synthetic chemistry to medical diagnosis. However, these methods suffer from low sensitivity. This means that only tens out of every million atomic nuclei in the sample being studied are actually detected. For example, the fraction of the 1H nuclei that are detected in standard NMR experiments is approximately 3.5 ppm (parts per million) for every Tesla of magnetic field that is applied. Therefore only relatively large quantities of substances can be investigated and expensive high-magnetic-field devices are required. One promising route to dramatically improving magnetic resonance is through the use of hyperpolarisation. This is the name given to methods that increasing the fraction of detected nuclei by factors of up to 100,000. In this work we focus on a method called SABRE (signal amplification by reversible exchange), which uses a special form of hydrogen gas, called parahydrogen (p-H2), to generate the hyperpolarisation effect. SABRE uses a transition metal complex to catalytically transfer polarisation from the p-H2 gas to a molecule of interest. This method has many exciting applications. For example, in clinical MRI, hyperpolarised agents have been injected into patients and then tracked to obtain diagnostic information about function and/or disease. This is only made possible by the hyperpolarisation, which allows the relatively small amount of the injected agent to be detected against the background of all of the other molecules in the body. Compared to other approaches, SABRE is a relatively new technology and so the underlying fundamental physics of the polarisation transfer process from p-H2 to the target molecule is poorly understood. Many theoretical models have been proposed but their simplifying assumptions are very difficult to test experimentally. This is because, in the standard approach, the detection stage of the SABRE experiment is separated in time and space from the polarisation stage, making direct interrogations of the transfer process challenging. Understanding SABRE is important not simply as an academic exercise. In order to transform SABRE into a universal hyperpolarisation technique, an efficient route to optimising the polarisation of new target molecules is required. Current empirical optimisation methods are time consuming, expensive, and not guaranteed to work. The central hypothesis of this work is that direct measurements of the SABRE effect carried out in situ - that is under the same conditions of magnetic field as where the polarisation transfer takes place - are the best route to developing a rigorous model for SABRE and thus enabling rational and rapid optimisation going forward. In this project, we will assemble a low-field (1 - 20 mT) NMR instrument that can be used as a platform to directly study the polarisation transfer process at the heart of SABRE. These experimental results will be combined with theoretical insights in order to devise a rigorous model that takes into account the many complexities of the SABRE process. This will lead to new strategies for polarisation transfer optimisation and consequently to an increase in the scope of SABRE applications in areas like medicine and industrial manufacturing.