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

转基因啮齿动物模型新型 MRI 采集技术的开发和验证

基本信息

批准号：
2114673
负责人：
金额：
--
依托单位：
University of Nottingham
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2114673
关键词：
Development validation novel MRI acquisition

项目摘要

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.

超极化是指用于在NMR实验中增加信噪比的几种技术。这是通过将角动量从电子转移到原子核以增强原子核极化来实现的。超极化技术的一个例子是动态核极化（DNP），它已被用于使用MRI非侵入性地研究活体心脏中的代谢变化。DNP以前曾与一系列用13 C标记的生物代谢物一起使用，为了超极化，将其冷却至低温（<1 K）并用微波照射。然后将样品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13 C的样本的一个问题是增强信号衰减的快速速率。由于这个原因，人们越来越关注使用硅作为MRI的超极化成像剂。超极化的29 Si粒子的衰变可以持续几个小时，这是比13 C的60- 120秒长得多的成像窗口。目前该领域的大部分工作都集中在硅微粒上。然而，这些具有有限的生物学应用，因为它们在组织中的分布受到它们的尺寸的限制，并且有可能阻塞注射部位附近的静脉。然而，纳米颗粒由于其较小的尺寸而可能具有更大的体内移动性。Kwiatkowski G等人（2017，Scientific reports，7（1），7946）报告了硅纳米颗粒的衰变为42分钟，并表明它们可用于通过MRI对活生物体进行成像。然而，据我们所知，还没有在生物体中使用超极化29 Si的报道。此外，硅颗粒具有灵活的表面化学性质，因此有可能载药，功能化和靶向。该项目有三个主要目标。第一个是优化超极化硅纳米颗粒的方案。一旦实现优化，即发现最大的信号增强，焦点将转向通过功能化使这些颗粒具有生物学用途。这项工作将与化学和药理学系合作进行。一个长期的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。虽然已经在优化硅纳米颗粒的信号方面做了一些工作，但在功能化方面做的工作很少。通过修饰纳米颗粒表面，可以进一步改善其生物分布和生物相容性。该项目属于EPSRC生物物理与软物质物理和医学成像研究领域的福尔斯。