Preserving hyperpolarised nuclear spin order to study cancer metabolism

Authors
Marco-Rius, Irene 

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Thesis
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Abstract

Monitoring the early responses of tumours to treatment is a crucial element in guiding therapy and increasing patient survival. To achieve this, we are using magnetic resonance imaging (MRI), which can provide detailed physiological information with relatively high temporal and spatial resolution. In combination with the dynamic nuclear polarisation (DNP) technique, high signal-to-noise is obtained, resulting in a powerful tool for in vivo 13C metabolic imaging. However, detection of hyperpolarised substrates is limited to a few seconds due to the exponential decay of the polarisation with the longitudinal relaxation time constant T1. This work aimed to improve the combination of hyperpolarisation and metabolic NMR/ MRI by extending the observation timescale of the technique. Working with quantum mechanical properties of the detected substrates, long lifetimes might be accessible by using the nuclear singlet configuration of two coupled nuclei. The singlet state is immune to intramolecular dipole-dipole relaxation processes, which is one of the main sources of signal decay in MRI. In favourable situations, the singlet relaxation time constant can be much longer than T1, so transfer of the polarisation into the singlet state may allow one to extend the usable time period of the nuclear hyperpolarisation. Here we studied the relaxation of hyperpolarised metabolites, including those found in the TCA cycle, and examined the possibility of extending their observation timescale by storing the polarisation in the long-lived singlet state. The polarisation remains in this state until it is eventually required for imaging. We also investigate how one may track polarised metabolites after injection into a subject due to the transfer of polarisation to the solvent by Overhauser cross-relaxation, so that the 13C polarisation remains untouched until imaging is required. In this way we should be able to interrogate slower metabolic processes than have been examined hitherto using hyperpolarised 13C MRS, and better understand metabolic changes induced in tumours by treatment.

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Keywords
DNP, Dynamic Nuclear Polarisation, Hyperpolarisation, Singlet state, Long-lived states, Pyruvate, Fumarate, Relaxation, SPINOE, T1
Qualification
Doctor of Philosophy (PhD)
Awarding Institution
University of Cambridge
Sponsorship
This work was supported by the European Union Seventh Framework Programme (FP7/2007-2013) under the Marie Curie Initial Training Network programme METAFLUX (project number 264780).