| The exchange of water between the intracellular and extracellular spaces plays a fundamental role in cellular function. It is also responsible for mixing the water magnetic resonance (MR) properties of those spaces and thus can have a profound effect upon attempts to perform compartment specific MR measurements of various physiological parameters. Therefore, understanding the process of transmembrane water exchange could greatly assist in the design and interpretation of numerous medically relevant MR measurements.; The aim of this thesis was to develop and execute a method for measuring the compartmental exchange rate constants for the in vivo mammalian (rat) brain. As water exchange cannot be directly observed, it was inferred indirectly by its effect upon the spin-lattice relaxation of water. While this method has previously been used in chemical exchange studies and to measure water exchange processes for cell and tissues in vitro , the extension to water exchange in the intact functioning mammalian brain poses a number of difficulties.; The water signal from the intracellular and extracellular compartments cannot be independently detected or perturbed and the inherent values of the spin-lattice relaxation rate constants (R1) in the two spaces are too similar to be differentiated. However, by cerebroventiicular infusion of Gd-DTPA, an extracellular relaxation agent, we enhance the R1 difference between compartments. Changes in the overall brain R1 were tracked as Gd-DTPA is naturally eliminated from the brain, allowing the exchange and relaxation rate constants for both compartments to be inferred using Bayesian probability theory.; This procedure was validated on a wide array of simulated data sets to determine the accuracy and precision of the estimated parameter values and the limitations of the analytical model. Various methods for rapidly collecting MRI spin-lattice relaxation data were evaluated on water phantoms and indicated that the technically difficult echo planar imaging was the method most compatible with our exchange measurement. Using this experimental protocol, the measured exchange rate constants for water leaving and entering the “brain” cell in vivo were 2 ± 1 s−1 and 10 ± 7 s−1, respectively. These values correspond to an intracellular water fraction of 0.8 ± 0.1, which is in good agreement with previous studies. In light of these results, numerous MR compartmental studies must be reevaluated to properly account for the effects of water exchange in the mammalian brain. |
