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Development of pulse sequences for hyperpolarized 13C magnetic resonance spectroscopic imaging of tumour metabolism



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Metabolic imaging with hyperpolarized 13C-labeled cell substrates is a promising technique for imaging tissue metabolism in vivo. However, the transient nature of the hyperpolarization - and its depletion following excitation - limits the imaging time and the number of excitation pulses that can be used. A single-shot 3D imaging sequence has been developed and it is shown in this thesis to generate 13C MR images in tumour-bearing mice injected with hyperpolarized [1-13C]pyruvate. The pulse sequence acquires a stack-of-spirals at two spin echoes after a single excitation pulse and encodes the kz-dimension in an interleaved manner to enhance robustness to B0 inhomogeneity. Spectral-spatial pulses are used to acquire dynamic 3D images from selected hyperpolarized 13C-labeled metabolites. A nominal spatial/temporal resolution of 1.25 x 1.25 x 2.5 mm3 x 2 s was achieved in tumour images of hyperpolarized [1-13C]pyruvate and [1-13C]lactate acquired in vivo. An advanced sequence is also described in this thesis in a later study to acquire higher resolution images with isotropic voxels (1.25 x 1.25 x 1.25 mm3) at no cost of temporal resolution. EPI is a sequence widely used in hyperpolarized 13C MRI because images can be acquired rapidly with limited RF exposure. However, EPI suffers from Nyquist ghosting, which is normally corrected for by acquiring a reference scan. In this thesis a workflow for hyperpolarized 13C EPI is proposed that requires no reference scan and, therefore, that does not sacrifice a time point in the dynamic monitoring of tissue metabolism. To date, most of the hyperpolarized MRI on metabolism are based on 13C imaging, while 1H is a better imaging target for its 4 times higher gyromagnetic ratio and hence 16 times signal. In this thesis the world’s first dynamic 1H imaging in vivo of hyperpolarized [1-13C]lactate is presented, via a novel double-dual-spin-echo INEPT sequence that transfers the hyperpolarization from 13C to 1H, achieving a spatial resolution of 1.25 x 1.25 mm2.





Brindle, Kevin


MRI, 13C, Hyperpolarized, Cancer, Metabolism


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge