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

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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.