The applicant's long-term career goal is to become an independent investigator in the field of magnetic resonance imaging (MRI) where she would like to concentrate her efforts to improve the diagnostic capability of the technique and understanding of the relationship between MRI parameters and human pathophysiology (with emphasis in cardiovascular problems). Thus, the goal of the proposed application is to gain hands-on experience in the technical aspects of clinical MRI by developing MRI techniques for the in vivo detection of structural changes in the arterial wall associated with pathological states, such as atherosclerosis, aneurysmal dilation, and hypertension. The project focuses on the development of MRI methods to detect subintimal lipid deposits and MRI methods that can accurately detect changes in the water component of the arterial wall in humans. Water-suppression, based on the differences in diffusion properties, spin-lattice relaxation times, and chemical shift between lipid and water spins, will be implemented for imaging subintimal lipids. These techniques will be used to image patients with atherosclerosis. MRI methods to accurately measure spin-spin relaxation (T2), extent of magnetization transfer, and diffusion will be implemented to image the water component of the arterial wall. The diffusion anisotropy of the arterial wall will be measured by MRI in patients with aneurysmal dilation in order to estimate the degree of organization of the elastin/collagen matrix. Changes in spin-spin relaxation times, extent of magnetization transfer, and diffusion will be measured in hypertensive and normotensive individuals and correlated with aortic compliance and severity of disease. To interpret the changes in MRI parameters in terms of changes in the structure of the arterial wall due to hypertension, the spontaneous hypertensive rat (SHR) will be used as an animal model of hypertension. MRI measurements will be carried out in the arteries of SHR and normotensive rats and correlated with in vivo arterial passive mechanical measurements and with the composition of the arterial wall. The project will be carried out under the sponsorship of Professor Arthur F. Gmitro, Ph.D., a physicist with extensive experience in medical imaging, and Professor Steven Goldman, M.D., a cardiologist with extensive experience in clinical research. Most of the project will be carried out at the Clinical MRI and Biological NMR facilities at the University of Arizona where the applicant will be working in an environment with MR technologists, cardiologists, radiologists, and physiologists. To obtain the necessary background for the research and training parts of the project, the applicant will take courses in medical imaging, electronics, and physiology during the first years of the grant.
