Hyperpolarized noble gases as biomarkers for pulmonary pathology

Lesbats, Clémentine (2017) Hyperpolarized noble gases as biomarkers for pulmonary pathology. PhD thesis, University of Nottingham.

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Hyperpolarized noble gas MRI using 3He and 129Xe has allowed void space imaging of the lungs for several years. Hyperpolarized 83Kr MRI has also been shown to provide an MRI contrast sensitive to the surface-to-volume ratio and chemistry of synthetic porous systems. Ex vivo animal models of pulmonary diseases and in vitro experiments were used in this thesis to examine three methodological advances allowing for the measurement of pulmonary physiological parameters using 129Xe and 83Kr.

The 83Kr quadrupolar property was explored in a rat model of pulmonary surface-to-volume ratio degradation, i.e. emphysema. The surface quadrupolar relaxation (SQUARE) of the noble gas provided maps of the longitudinal relaxation in control and emphysematous rat lungs. The relaxation observations were regionally correlated to the histological measurements of the alveolar degradation.

The 129Xe solubility in the lungs, blood, and more generally liquids, was the basis for the design of a new biosensor composed of a cryptophane cage tethered to a paramagnetic agent. The depolarization of the 129Xe atoms encapsulated by the cryptophane, followed by chemical exchange with the surrounding medium was investigated in vitro. This model biosensor will lead to a future switchable biosensor that will be deactivated by the enzymatic cleavage of the encapsulating cage and the paramagnetic agent.

Finally, the 129Xe solubility was further utilised to study the gas transfer through ex vivo rat lungs after blood replacement by a perfluorocarbon emulsion. The large chemical shift separating the 129Xe peaks for the gas phase, the tissue and the perfluorocarbon emulsion, allowed for a selective excitation of each phase and the independent observation of their signal build-up after inhalation. This mechanism will be used as a biomarker for gas transfer impairment in animal models of pulmonary fibrosis.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Meersmann, T.
Johnson, S.R.
Pavlovskaya, G.
Keywords: MRI; NMR; Hyperpolarized; Gases; Xenon; Krypton; Pulmonary
Subjects: W Medicine and related subjects (NLM Classification) > WF Respiratory system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 42321
Depositing User: LESBATS, Clémentine
Date Deposited: 16 Oct 2017 13:35
Last Modified: 17 Oct 2017 20:34
URI: https://eprints.nottingham.ac.uk/id/eprint/42321

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