Contrast in NMR images arises primarily from the heterogeneous distribution of tissue relaxation properties, but the mechanisms by which NMR properties alter in disease states are poorly understood. In these studies, a systematic attempt will be made to comprehend and quantify the relaxation mechanisms in a single tissue, (rat liver) in both normal and diseased states. The methods used will be of general application and will be used to construct a model of the relaxation behaviour of other tissues. To accomplish this, NMR studies will be performed in vitro on preparations of isolated constituents of tissue to evaluate the significance of content alone and to quantify the relative efficacy of different macromolecules. Studies will also be performed on excised rat liver from normal animals as well as models of liver disease in which diverse alterations are expected. The NMR experiments will unravel which relaxation mechanisms are significant at the molecular level. Nuclear overhauser effects and deuterium quadrupolar relaxation rates in deuterated samples will be used to measure the contribution of non-dipolar mechanisms and to estimate the effective correlation time of tissue water. High resolution proton spectra of intact and deuterated tissues will reveal the behaviour of non-exchanging compartments. Saturation transfer and selective irradiation will be used to evaluate the contributions of chemical exchange and cross relaxation. Low temperature studies of the non-freezing tissue water will be used in combination with deuteration studies and NMR relaxation dispersion profiles over the range 10KHz - 100 MHz to quantify individual populations of protons, their mutual effects and correlation times. These measurements will be correlated with biochemical assays of tissue samples and repeated in rat models of normal, developing, regenerating, ischemic, malignant, cirrhotic and fatty livers. Animal imaging studies will also be performed on live rats at 85 MHz by recording chemical shift resolved images of liver. The normal liver and macromolecular studies will permit a thorough understanding of in vivo relaxation behaviour, and the animal model studies will provide experimental situations for evaluating the detailed nature of the changes in NMR parameters that accompany biochemical alterations in tissue.
Showing the most recent 10 out of 44 publications
