Development and validation of novel MRI acquisition techniques for transgenic rodent models

超极化是指在核磁共振实验中用来提高信噪比的几种技术。这是通过将角动量从电子转移到原子核来增强核极化来实现的。超极化技术的一个例子是动态核极化(DNP)，它已经被用于通过核磁共振非侵入性地研究活心脏的代谢变化。DNP以前曾与一系列标有13C的生物代谢物一起使用，如果超极化，这些代谢物被冷却到低温(1K)，并用微波照射。然后，样品被熔化并注射到动物或人体内，从而能够在体内研究代谢途径。基于13C的样本的一个问题是增强信号衰减的速度太快。因此，人们对使用硅作为核磁共振超极化成像剂的兴趣与日俱增。超极化的29Si粒子的衰变可以持续几个小时，这比13C的60-120秒的成像窗口要长得多。目前该领域的大部分工作都集中在硅微粒上。然而，这些药物的生物学应用有限，因为它们在组织中的分布受到它们大小的限制，而且有可能堵塞注射部位附近的静脉。然而，纳米颗粒由于尺寸较小，在体内可能具有更大的流动性。Kwiatkowski G等人(2017，Science Reports，7(1)，7946)报告了硅纳米颗粒的衰变时间为42分钟，并表明它们可用于通过核磁共振对活体进行成像。然而，据我们所知，还没有关于在生物体内使用超极化29Si的报道。此外，硅颗粒具有灵活的表面化学，因此有可能载药、功能化和靶向。这个项目有三个主要目标。第一个是优化硅纳米颗粒的超极化方案。一旦实现了最优化，即发现了最大的信号增强，重点将转向通过功能化使这些粒子具有生物用途。这项工作将与化学和药理学系合作完成。一个长期目标是在活体动物模型中使用这些功能化的超极化纳米颗粒。尽管人们已经在优化来自硅纳米颗粒的信号方面做了工作，但在功能化方面做的工作很少。通过对纳米颗粒表面的修饰，可以进一步改善其生物分布和生物相容性。该项目属于EPSRC生物物理、软物质物理和医学成像研究领域。

Hyperpolarisation refers to several techniques used to increase the signal to noise ratio in NMR experiments. This is achieved by transferring angular momentum from electrons to nuclei to enhance nuclear polarisation. An example of a hyperpolarisation technique is Dynamic Nuclear Polarisation (DNP) which has been used to non-invasively study metabolic changes in the living heart using MRI. DNP has previously been used with a range of biological metabolites labelled with 13C which, to hyperpolarise, are cooled down to low temperatures (<1K) and irradiated with microwaves. The sample is then melted and injected into an animal or person enabling metabolic pathways to be studied in vivo. One issue with 13C based samples is the rapid rate with which the enhanced signal decays. For this reason, there is increasing interest in using silicon as a hyperpolarised imaging agent for MRI. The decay of hyperpolarised 29Si particles can last a couple of hours which is a much longer imaging window than the 60-120s of 13C. Much of the current work in the field has been focussed on silicon microparticles. These, however, have limited biological application as their distribution in tissue is restricted by their size and there is the potential to block veins near the site of injection. Nanoparticles, however, are likely to have greater in vivo mobility due to their smaller size. Kwiatkowski G, et al (2017, Scientific reports, 7(1), 7946) reported the decay of silicon nanoparticles as 42 minutes and showed they could be used for imaging living organisms by MRI. To our knowledge, however, there are no reports of using hyperpolarised 29Si in living organisms. In addition, silicon particles have flexible surface chemistry and so there is the potential to drug load, functionalise and target. There are three main aims for this project. The first is to optimise the protocol for hyperpolarising the silicon nanoparticles. Once optimisation has been achieved, i.e. the largest signal enhancements found, the focus will turn to making these particles biologically useful by functionalisation. This work would be done in collaboration with the Departments of Chemistry and Pharmacology. A long-term aim would be using these functionalised, hyperpolarised nanoparticles in living animal models. Although work has already been done on optimising the signal from silicon nanoparticles, little work has been done on the functionalisation. By modifying the nanoparticle surface their biodistribution and biocompatibility could be further improved. This project falls within the EPSRC Biophysics & Soft Matter Physics and Medical Imaging research areas.