The overall aims of this project are to understand quantitatively the relationships between tissue iron levels and nuclear magnetic resonance (NMR) properties in order to develop a method for rigorously measuring iron in the brain, liver, and other organs. Iron is a physiologically vital substance, but it also can be toxic and has been associated with numerous pathological states in various tissues. As summarized in the report of a recent NIDDK workshop, the only established, calibrated method for non-invasive measurement of tissue iron stores is currently biomagnetic susceptometry using Superconducting Quantum Interference Device (SQUID) magnetometers, but the cost, complexity, and technical demands limit access to this technique. Many previous studies have indicated that magnetic resonance imaging (MRI) can detect iron loading, but no clear protocol has been established to measure iron content in tissue accurately. While NMR can readily detect a variety of signal parameters that depend upon the iron content of tissue, the exact dependence of these parameters (e.g. T1, T2, T2*, T2', delta/omega on the concentration and form of the stored iron is complex and unclear. This problem can be addressed only by combining studies of iron metabolism with studies of fundamental nuclear relaxation mechanisms and the development of advanced MRI measurement protocols. Our group at Vanderbilt is uniquely qualified for such an approach. We propose to combine the study of an animal model of iron overload, advanced NMR techniques, and high-resolution SQUID susceptibility imaging. These experiments, in combination with computer simulations, will allow the detailed, quantitative comparison of biomagnetic and NMR data from individual animals whose tissue iron content can be determined quantitatively at the end of each experiment