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Development of Optimised Pulse Sequences for Magnetic Resonance Imaging of Tumour Metabolism 10.17863/CAM.90049 Somai, Vencel 000000019874526X Brindle, Kevin Development of efficient pulse sequences for hyperpolarised 13C imaging: Dynamic nuclear spin polarization of 13C-labeled cell substrates has enabled dynamic measurements of tissue metabolism in vivo using 13C MRSI. The principal limitation of the technique is the short lifetime of the hyperpolarisation, which requires the use of very fast imaging methods. As well as being fast the imaging pulse sequence must make economical use of the polarisation since each excitation pulse results in depletion of the polarisation, in addition to that due to T1- dependent decay, which degrades the SNR and decreases the time window over which metabolism of the labelled substrate can be monitored. A single shot 3D multi spin echo pulse sequence with optimised RF pulses was designed in response to these requirements with the aim of clinical translatability. Monitoring tumour cell death using 2H magnetic resonance spectroscopy and spectroscopic imaging: 2H magnetic resonance spectroscopic imaging (MRSI) has been shown recently to be a viable technique for metabolic imaging in the clinic. The relatively low sensitivity of 2H detection is compensated by its very short T1, which means that signal can be acquired rapidly without saturation. Production of [2,3-2H2]malate, following injection of [2,3- 2H2]fumarate (1g/kg) into tumour-bearing mice was measured in various tumour models using surface-coil localized 2H MR spectroscopy at 7T. Malate production was also imaged in EL4 tumours using a fast 2H chemical shift imaging sequence. The possibility of detecting tumour cell death in vivo by means of monitoring [2,3-2H2]malate production from [2,3-2H2]fumarate was demonstrated. As a related pulse design problem, the possibility of reducing the power requirement of the RF pulses used in such experiments by means of numerical optimal control was investigated. Genetic algorithm-based pulse sequence optimisation: The performance of pulse sequences in vivo can be limited by fast relaxation rates, magnetic field inhomogeneity and non-uniform spin excitation. A simple method for pulse sequence optimisation is presented that uses a stochastic numerical solver which, in principle, is capable of finding a better local optimum. The method provides a simple framework for incorporating any constraint and implementing arbitrarily complex cost functions. Efficient methods for simulating spin dynamics and incorporating frequency selectivity are also described. The proposed technique is evaluated with common pulse design problems where a high-quality solution is not yet readily available, such as robust heteronuclear polarisation transfer experiments, excitation pulse design with special requirements e.g. insensitivity to B1-inhomogenity while maintaining a low B1- amplitude and rapid water suppression. The aim was to minimize pulse amplitudes so as to keep the deposited energy as low as possible, which would then allow clinical translation. University of Cambridge 2022-06-03 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/342635 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/db03be98-eba1-4640-9054-2ab18292778b/download 52bee6dac525c29216a33bfac100185f https://www.rioxx.net/licenses/all-rights-reserved/ Deuterium Hyperpolarised MRI Optimisation Tumour