Iron overload is a systemic disorder and is either primary (genetic) or secondary (exogenous iron administration). Primary iron overload is most commonly associated with hereditary hemochromatosis and secondary iron overload with ineffective erythropoiesis that requires long-term transfusion therapy, leading to transfusional hemosiderosis. Iron overload may lead to liver cirrhosis and hepatocellular carcinoma, in addition to cardiac and endocrine complications. The liver is one of the main iron storage organs and the first to show iron overload. Therefore, detection and quantification of liver iron overload are critical to initiate treatment and prevent complications.
Iron overload is characterized by a high level of plasma iron and accumulation of iron in parenchymal cells in the form of ferritin and hemosiderin. In the event of iron overload, the transferrin saturation can exceed 45% (normal range, 20%–45%), at which point non–transferrinbound iron is created, which has a high affinity for parenchymal cells, especially hepatocytes. Eventually, if the transferrin saturation exceeds 75%, a new form of non–transferrin-bound iron is produced—labile plasma iron—which has the potential to produce toxic reactive radicals. When not immediately needed, iron is stored in its ferric form (Fe3+) within ferritin and eventually within hemosiderin if ferritin storage is saturated(Fig.1).
Fig. 1: Iron (Fe) metabolism. Absorption of oral iron intake occurs in the duodenum, near the gastroduodenal junction. Hemochromatosis is caused by a defect in the HFE gene. In hemochromatosis, iron overload is predominantly distributed in the hepatocytes in the liver and eventually in other organs, predominantly in the β cells in the pancreas and in the heart. Hemosiderosis is caused by repeated blood transfusions, typically in sickle cell disease and β-thalassemia major. In hemosiderosis, iron overload is concentrated in the reticuloendothelial system, predominantly the spleen, bone marrow, and Kupffer cells in the liver. Hemolysis in hemolytic anemias can lead to iron accumulation in the proximal convoluted tubules of the kidneys.
References: Roxanne Labranche, Guillaume Gilbert, Milena Cerny et al, Liver Iron Quantification with MR Imaging: A Primer for Radiologists RadioGraphics 2018; 38:392–412
MR imaging is the best non invasive method for measuring the level of iron in the liver for the purposes of confirming the diagnosis, determining the severity, and monitoring therapy with high sensitivity, specificity, and positive and negative predictive values. The accumulation of iron ions in the tissues, because of the superparamagnetic properties of the ions, causes local distortion in the magnetic fields and relaxation of the spins, which results in shortening of the longitudinal relaxation time (T1), the transverse relaxation time (T2) and particularly the transverse relaxation time as affected by magnetic field inhomogeneity (T2*)(Fig.2). This effect causes a loss of signal intensity in the affected organs that is proportional to the iron deposition.