Recent work by several investigators working on different problems in our laboratory has shown the novel MR imaging techniques which are sensitive to magnetic susceptibility effects can provide unique information about the underlying pathological anatomy and physiology that cannot be obtained with conventional MR imaging methods. Two broad classes of magnetic susceptibility effects have been shown to be important. 1) alterations in endogenous iron content and biochemistry and 2) perfusion sensitive microscopic susceptibility variations following administration of paramagnetic contrast agents. The purpose of this Program Project Grant is to provide for a coordinated investigation for the implications of these effects for enhancing the utilization and improving the diagnostic specificity of MR imaging in a variety of organ systems and pathological states, including cancer, ischemia, hemorrhage and thrombosis. This proposal is divided into five research projects, each focused on a separate problem but sharing Core resources and with considerable overlap of methodologies and personnel to allow for constructive interaction. The five are: 1) MR brain studies of normal, ischemic and neoplastic tissues bases on transient magnetic susceptibility effects of paramagnetic contrast agents and on the intrinsic effects of flow in capillaries; 2) MR studies in normal and ischemic myocardium based on magnetic susceptibility effects, and also on the relativity effects, of paramagnetic contrast agents; 3) Serial multinuclear MR imaging of hemorrhage with biochemical, EPR and histopathologic correlates; 4) Magnetic susceptibility- sensitive and flow-sensitive imaging of deep venous thrombosis with biochemical correlation; and 5) Comparison of various contrast agents using conventional and magnetic susceptibility-sensitive imaging techniques for optimal detection and characterization of liver metastases. These projects are supported by three Core laboratories: NMR Core Computer and Technologies Core, Contrast Agent Core, and an Administrative Core.