Towards micro-imaging with dissolution dynamic nuclear polarisation

Nuclear magnetic resonance (NMR) of small samples and nuclei with a low gyromagnetic ratio is intrinsically insensitive due to the received signal dependence on Boltzmann's statistics. This insensitivity can be partially overcome through the application of hyper polarisation techniques such as...

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Main Author: Gaunt, Adam P.
Format: Thesis (University of Nottingham only)
Language:English
Published: 2018
Subjects:
Online Access:https://eprints.nottingham.ac.uk/51219/
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author Gaunt, Adam P.
author_facet Gaunt, Adam P.
author_sort Gaunt, Adam P.
building Nottingham Research Data Repository
collection Online Access
description Nuclear magnetic resonance (NMR) of small samples and nuclei with a low gyromagnetic ratio is intrinsically insensitive due to the received signal dependence on Boltzmann's statistics. This insensitivity can be partially overcome through the application of hyper polarisation techniques such as Dissolution Dynamic Nuclear Polarisation (D-DNP). It is hoped that the hyper polarised 13C signal received from labelled small molecules could facilitate imaging of metabolic and transporter processes in biological systems. In order to realise this, appropriate molecules and experimental hardware must be used. A detailed description of the experimental set-up used for carrying out DDNP is given and the system is characterised. the advantageous use of a dual iso-centre magnet system is elucidated with optimisation of acquisition of fast relaxing molecules. such a system allows for interrogation of processes with short relaxation times, not possible with traditional, stand-alone polarisers. To acquire the maximum amount of hyper-polarised 13C signal in an imaging experiment, parallel acquisition techniques have been implemented and the hardware designed with such goals in mind. Multiple coils have been used to allow accelerated image acquisition. As such this work has validated the SENSE algorithm for artefact free, image reconstruction on the micro-scale. These techniques require an array of coils which add to the complexity of the design of the probehead. Decoupling methods and array coil construction must be considered the methods used to ensure well isolated coils, such as geometric decoupling, are presented. The novel fabrication and implementation of micro-coils for imaging and spectroscopy of nL scale samples is presented this will help facilitate the acquisition of images showing metabolic processes in active transport in cells. By placing the coils close to the sample it is possible to gain sensitivity relative to the mass of the sample in question. To achieve signal detection on the order of nL a novel, exible micro-coil array has been fabricated and the results of NMR experiments carried out on both protons and 13C are shown. This is the final stage before integrating the coils with the D-DNP system. The acquisition of 13C signal with the micro-coils displays optimal electronic characteristics when compared with other detectors presented in the literature. The final goal of the work is to produce a system that is capable of micro imaging in small biological samples such as the Xenopus Oocyte with a view to monitoring metabolic processes and transportation without the need for the use of the large fluorescing proteins (GFP's) that have been used in previous work (1). The need for GFP's attached to metabolites results in the measured data being non-physical as the fluorescing protein is often much larger than the molecule being transported. It is hoped that the use of hyperpolarised small molecules (such as pyruvic acid) may be able to remove this need for GFP's in the study of metabolite transportation.
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spelling nottingham-512192025-02-28T12:03:51Z https://eprints.nottingham.ac.uk/51219/ Towards micro-imaging with dissolution dynamic nuclear polarisation Gaunt, Adam P. Nuclear magnetic resonance (NMR) of small samples and nuclei with a low gyromagnetic ratio is intrinsically insensitive due to the received signal dependence on Boltzmann's statistics. This insensitivity can be partially overcome through the application of hyper polarisation techniques such as Dissolution Dynamic Nuclear Polarisation (D-DNP). It is hoped that the hyper polarised 13C signal received from labelled small molecules could facilitate imaging of metabolic and transporter processes in biological systems. In order to realise this, appropriate molecules and experimental hardware must be used. A detailed description of the experimental set-up used for carrying out DDNP is given and the system is characterised. the advantageous use of a dual iso-centre magnet system is elucidated with optimisation of acquisition of fast relaxing molecules. such a system allows for interrogation of processes with short relaxation times, not possible with traditional, stand-alone polarisers. To acquire the maximum amount of hyper-polarised 13C signal in an imaging experiment, parallel acquisition techniques have been implemented and the hardware designed with such goals in mind. Multiple coils have been used to allow accelerated image acquisition. As such this work has validated the SENSE algorithm for artefact free, image reconstruction on the micro-scale. These techniques require an array of coils which add to the complexity of the design of the probehead. Decoupling methods and array coil construction must be considered the methods used to ensure well isolated coils, such as geometric decoupling, are presented. The novel fabrication and implementation of micro-coils for imaging and spectroscopy of nL scale samples is presented this will help facilitate the acquisition of images showing metabolic processes in active transport in cells. By placing the coils close to the sample it is possible to gain sensitivity relative to the mass of the sample in question. To achieve signal detection on the order of nL a novel, exible micro-coil array has been fabricated and the results of NMR experiments carried out on both protons and 13C are shown. This is the final stage before integrating the coils with the D-DNP system. The acquisition of 13C signal with the micro-coils displays optimal electronic characteristics when compared with other detectors presented in the literature. The final goal of the work is to produce a system that is capable of micro imaging in small biological samples such as the Xenopus Oocyte with a view to monitoring metabolic processes and transportation without the need for the use of the large fluorescing proteins (GFP's) that have been used in previous work (1). The need for GFP's attached to metabolites results in the measured data being non-physical as the fluorescing protein is often much larger than the molecule being transported. It is hoped that the use of hyperpolarised small molecules (such as pyruvic acid) may be able to remove this need for GFP's in the study of metabolite transportation. 2018-07-19 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/51219/1/thesis_corrected_170418.pdf Gaunt, Adam P. (2018) Towards micro-imaging with dissolution dynamic nuclear polarisation. PhD thesis, University of Nottingham. NMR MRI Micro-imaging DNP Dissolution-DNP Microfabrication micro coil. NMR-microscopy
spellingShingle NMR
MRI
Micro-imaging
DNP
Dissolution-DNP
Microfabrication
micro coil. NMR-microscopy
Gaunt, Adam P.
Towards micro-imaging with dissolution dynamic nuclear polarisation
title Towards micro-imaging with dissolution dynamic nuclear polarisation
title_full Towards micro-imaging with dissolution dynamic nuclear polarisation
title_fullStr Towards micro-imaging with dissolution dynamic nuclear polarisation
title_full_unstemmed Towards micro-imaging with dissolution dynamic nuclear polarisation
title_short Towards micro-imaging with dissolution dynamic nuclear polarisation
title_sort towards micro-imaging with dissolution dynamic nuclear polarisation
topic NMR
MRI
Micro-imaging
DNP
Dissolution-DNP
Microfabrication
micro coil. NMR-microscopy
url https://eprints.nottingham.ac.uk/51219/