Quantification of dispersed and aggregated iron in vivo by magnetic resonance imaging

This work is a comprehensive validation of a novel magnetic resonance (MR) based iron measurement technique that can separately determine in vivo tissue concentrations of dispersed (ferritin-like) and aggregated (hemosiderin-like) iron. A variety of blood disorders, including thalassemia, sickle-cell disease, aplastic anemia, and myelodysplasia require patients to have chronic blood transfusions as part of standard treatment. Because the body lacks any physiological mechanism for the excretion of excess iron, the iron within the transfused red blood cells is progressively deposited in the liver, heart, endocrine and other organs. With carefully monitored iron-chelation therapy, these patients can often avoid organ failure and early death from iron toxicity. For this reason, new non-invasive techniques are sought to evaluate iron levels throughout the body. Though conventional methods exist to determine total hepatic iron levels, such as biopsy and biomagnetic susceptometry, there are almost no quantitative methods to investigate the life-threatening complication of cardiac iron overload. MR imaging has proven promising in assessing myocardial iron deposition, due to its unique sensitivity to paramagnetic materials. In this investigation we develop an MR-based iron measurement method that can additionally determine the separate concentrations of dispersed and particulate iron. The body stores iron in two molecular forms, hemosiderin, a particulate and insoluble fraction, and ferritin, a dispersed and soluble fraction. Both forms are nontoxic, however, their relation to iron toxicity is an area of intensive investigation at the moment, not least because chelation treatment may affect the concentration of these storage forms differently. We perform here a validation of our MR-iron quantification model on artificial phantoms, human liver ex vivo, and thalassemia patients in vivo. This robust and non-invasive method to measure hemosiderin and ferritin iron could improve our ability to monitor the chelation therapy of individual patients and also may lead to a better understanding of chelator efficacy