The proposed research will integrate radiological, clinical and laboratory efforts in the development and validation of quantitative magnetic resonance methods for the measurement of heart and liver iron. We propose to acquire a fundamental theoretical and physical understanding of the resonance effects of tissue iron as a guide in the development of novel MR techniques that will provide clinically applicable methods for the quantitative measurement of hepatic and cardiac iron. These studies will take advantage of a unique convergence of resources and expertise at Columbia University, including the Hatch MR Research Center, active programs of liver and heart transplantation, the Iron Reference Laboratory, and the SQUID biosusceptometry facility where hundreds of patients with diverse forms of iron overload are seen each year. The proposed research has three specific aims: (1) to investigate systematically in and ex vivo the resonance behavior of ferritin and hemosiderin iron in diverse hepatic and cardiac disorders in patients undergoing organ transplantation, using candidate MR methods including conventional spin- and gradient-echo sequences, spectroscopic techniques, and projection reconstruction-based pulse sequences designed to facilitate capture of short T2* components; and ( 2 ) to examine selected MR methods for measurement of hepatic and cardiac iron in patients with iron overload of diverse severity and etiologies (hereditary hemochromatosis, chronic transfusion for thalassmia major, sickle cell disease, aplastic and other refractory anemia) in conjunction with SQUID biosusceptometry in vivo, magnetic susceptometry ex vivo, ultrastructural and biochemical studies of explant tissue; and (3) to prospectively validate optimized MR measurements of hepatic and cardiac iron concentrations with the results of biochemical analysis of tissue from heart and liver explants in series of adult and pediatric patients with and without disorders affecting iron metabolism. The development of validated, clinically applicable MR methods for the non-invasive measurement of hepatic and cardiac iron would be a major advance in the diagnosis and management of patients with iron overload that would find immediate and widespread diagnostic use both in the U.S. and worldwide.
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