MRI Quantitation of Tissue Iron in Hematologic Disorders

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DESCRIPTION (provided by applicant): Chronic iron overload leads to increased iron deposition in tissues. In chronically-transfused thalassemia patients, exogenous iron is stored in the spleen, liver, endocrine organs and heart. By contrast, in hereditary hemochromatosis iron overload occurs as a result of excessive absorption of iron from the diet. In both diseases, control of iron levels below the toxic threshold is essential. Further, since serum ferritin levels do not parallel tissue iron levels, periodic liver biopsies have to be performed. The invasive nature of this procedure calls for alternative, less traumatic approaches for multi-organ iron screening. Here we propose to implement, validate and apply to patients with thalassemia, a MRI-based quantitative tissue iron mapping technique focusing on the liver and heart, to evaluate the hypothesis that tissue iron levels can be measured accurately and reproducibly. The method is based on the GESFIDE imaging technique developed in the investigators' laboratory. This method allows efficient measurement of T2'and T2, the RF-reversible and RF-irreversible transverse relaxation times, both known to be reduced at elevated tissue iron levels. The following specific aims will be pursued: 1. We shall fully develop and implement improved GESFIDE MRI iron mapping technique at 1.5 and 3T and examine its performance in human volunteers. 2. We shall evaluate the method's accuracy on specimens of a murine model of thalassemia in comparison to chemical assay. 3. We shall, in a pilot study of 30 patients with thalassemia, measure iron levels in the heart and liver at three time points during a three-year observation period and compare the results with liver biopsy data and to results in age- and gender-matched controls. 4. We shall, in the patients of specific aim #3, evaluate cardiac function by MR to test the hypothesis that the severity of impaired function is associated with the degree of cardiac iron overload.