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Towards Detection of Intracellular Calcium Flux by Magnetic Resonance Imaging.

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Magnetic resonance imaging is a powerful research tool for studying anatomical processes in intact large organisms, as it is capable of generating high resolution images with unlimited penetration depth and excellent soft-tissue contrast. However one of the challenges faced by those seeking to use the technique to answer biochemical questions, is the inherent low sensitivity towards responsive probes. This requires careful selection of the model system and pathways to be investigated. The work in this thesis was aimed at expanding the research space accessible to magnetic resonance imaging methods to include detection of activity in the central nervous system. Specifically, visualization of intracellular calcium flux. This could provide a means for studying fundamental signaling information in deep brain regions inaccessible to other imaging techniques. Towards this aim, an existing calcium-sensitive agent was evaluated in two unique animal models: cannulation in rats and microinjection in mice. Learning from the shortcomings of this agent in vivo, new calcium responsive agents designed to have enhanced cellular permeability were synthesized and subjected to preliminary characterization.

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