This proposal aims to continue studies to better understand the physical factors that affect the NMR relaxation properties of protons in tissues and which determine contrast in MR images.
We aim to better understand what influences the fundamental processes involved in relaxation in tissues at the molecular level. We have provided evidence of the role of magnetization transfer (MT) in tissue-like model systems, and have shown how this depends on both chemical exchange and cross-relaxation, physico-chemical effects and macromolecular structure. This evidence has been derived by developing new and improved methods of measuring MT.
We aim to extend these studies to other systems and tissues, and to more fully explore the molecular structural factors that influence MT and spin diffusion, and their roles in relaxation. This will include studies of the effects of surface groups, pH, and matrix rigidity. We will use novel quantitative methods of characterizing MT in media with different degrees of deuteration, along with new methods sensitive to T1rho, to derive measures of the sizes and motional characteristics of proton pools within samples. We will use these measurements to examine the number of compartments required to fully explain MT data. We will also directly address questions of the importance of MT versus spin locking and direct saturation effects. We will investigate the degree to which MT in tissues and model systems is limited by rates of water diffusion, by studying the effects of diffusion on displacement profiles of water using novel pulse gradient spin echo methods. Finally, we will try to detect and investigate the influence of water that is preferentially oriented and rotating anisotropically, using magic angle radiofrequency field techniques. We will explore the use of stimulated echo measurements of dipolar correlation effects and multiple quantum filter techniques that are sensitive to macroscopic order and relatively long time-scale residual dipolar couplings that are not motionally averaged and which may account for the shortening of T2 in tissues. We will study a selected group of tissues, biopolymers and gels, in different conditions and of varied composition. Overall this project should provide many new insights into tissue relaxation phenomena to aid in the better understanding of the origin of contrast in NMR images. This should in turn provide guidance on the interpretation of signals in conventional MR images and will motivate new approaches to tissue characterization.
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