Rega, M; (2015) Investigation of Endogenous Chemical Exchange Saturation Transfer Effects with Magnetic Resonance Imaging in Various Animal Models of Neurological Disorders. Doctoral thesis , UCL (University College London).

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Abstract

Chemical Exchange Saturation Transfer (CEST), is an emerging Magnetic Resonance Imaging (MRI) technique. CEST indirectly measures exchangeable protons contained in either endogenous or exogenous compounds by measuring the water signal reduction due to magnetisation exchange between these compounds and the surrounding water. CEST offers sensitivity enhancement compared to any method which directly measures these compounds. The complexity of the CEST signal in-vivo limits direct quantitative interpretation. However, the technique is inherently sensitive to a range of physiological parameters, such as temperature, pH and metabolite concentration. In order to investigate the relative importance of these different contributing factors, the work described in this thesis used the Bloch-McConnell equation system to model the CEST effect, for CEST sequence optimisation and data interpretation. Bovine Serum Albumin (BSA) phantoms were scanned with a CEST sequence and the results were compared to standard contrast methods (T1, T2). The CEST effects were correlated with changes in environmental pH, temperature and metabolite concentration. Next, a spectroscopic CEST sequence was implemented for spinal cord CEST and two models of neurodegenerative diseases were investigated. First, a model of Amyotrophic Lateral Sclerosis (ALS), revealed no changes in the CEST signal over the time course of the disease; the finding matched post-mortem soluble protein concentration analysis. Second, a model of Spinal and Bulbar Muscular Atrophy (SBMA), revealed no changes in the CEST signal of affected mice scanned at 10 and 12 months of age. However, changes in the CEST signal were observed in control mice and this again agreed with post-mortem protein concentration analysis. Finally, the potential for CEST to measure regional pH changes in a piglet model of Hypoxic Ischemia (HI) was investigated. CEST data were compared and found to agree with 31P MRS, measuring intracellular pH (pHi) and 1H MRS, measuring cerebral lactate levels.

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