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Magnetic resonance spectroscopy (MRS) is limited by low signal strength at thermal equilibrium owing to low spin polarisation. NMR spectroscopy and MR spectroscopic imaging are therefore subject to constraints in both spatial and temporal resolution, especially for nuclei other than 1H, owing to their lower natural abundance and lower gyromagnetic ratio. In recent years there have been advances in hyperpolarisation technologies, in particular dissolution dynamic nuclear polarisation (DNP), which has enabled significant NMR signal enhancements of low gyromagnetic ratio nuclei, such as 13C and 15N, in a range of endogenous biological metabolites. This has provided a number of opportunities, hitherto inaccessible, to measure the inter-conversion of metabolites in real time in cellular systems, whole organ preparations, as well as in vivo, and thereby to report on the activity of endogenous enzymes and membrane transporters that facilitate their kinetic inter-conversion. We provide an overview of the methods available for hyperpolarising small molecule metabolites and discuss application areas for their biomedical exploitation as well as some of the limitations of the methodology.

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