Demetriou, Eleni; (2018) Effects of exchange rate on chemical exchange saturation transfer. Doctoral thesis (Ph.D), UCL (University College London).

Abstract

The general work presented in this thesis describes the implementation and optimization of CEST MRI techniques on a preclinical 9.4 T MRI scanner for quantifying the chemical exchange rate or the exchange relaxation term both in vitro and in pathological conditions. A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (PROgressive saturation for Quantifying Exchange rates using Saturation Times) has been developed. A complete theoretical framework has been set up, and the exchange rates calculated in several aminoacids using PRO-QUEST were compared and found in good agreement with standard methods. A reduction of scan time from 58min to 16min has been obtained using PRO-QUEST for measurement in both healthy and infarcted rat after 24 hours and revealed that imaging specificity to ischemic acidification was substantially increased relative to standard APT-weighted imaging. The second part of this thesis describes the development of CEST contrast agents based on liposome encapsulation. For this work a concise analytical model has been developed for characterizing the liposomal contrast. In addition, combining this analytical model with measurements of the CEST signal enhancement using liposomes as a model membrane system provides a new technique for studying membrane permeability. All theoretical developments are included as part of this second major chapter. The final part of the thesis describes applications of CEST and high-resolution magnetic resonance spectroscopy for studying prion protein misfolding and neurodegeneration in Prion disease. Here alterations in CEST signal are detected before structural changes or any clinical signs of Prion disease, most likely based on changes in exchange rates, which is encouraging for translation of CEST imaging for early detection of neurodegenerative processes. Thus, CEST signal displays different patterns at different stages of the disease indicating the potential of using CEST to separate different groups of Prion-infected mice.

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