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Magnetic resonance imaging (MRI) provides a noninvasive, quantitative method of estimating parenchymal iron levels. In principle, MRI can be used to quantify iron stores wherever they exist in the body. In practice, MRI has been investigated in the assessment of hepatic, cardiac, and anterior pituitary iron stores.

How MRI measures iron stores

MRI measures tissue iron concentration indirectly via the detection of the paramagnetic influences of storage iron (ferritin and hemosiderin) on the proton resonance behavior of tissue water (1). The longitudinal (R1) and transverse (R2) nuclear magnetic relaxation rates of nearby solvent water protons can then be calculated. Both R1 and R2 rates are increased when interacting with paramagnetic particles such as iron. R2 (or spin-echo imaging) is preferable to R1 for determining LIC, since ferritin enhances the relaxation of both R1 and R2, while hemosiderin only has a strong R2 relaxation accelerating effect. Gradient echo imaging produces images for calculating T2* and R2*, where R2* = 1000/T2*. A T2* of 20 ms is equivalent to an R2* of 50 Hz.

MRI detection of hepatic iron overload

MRI provides a non-invasive alternative to liver biopsy, and may actually be more accurate in patients with heterogeneous liver iron deposition (such as those with cirrhosis) since it measures iron in the whole organ. In addition, the pathologic status of the liver can also be assessed using MRI.

An MRI image (R2 map, inverse, false color) clearly displays iron-overloading in the liver.

Accuracy of LIC assessment

Liver iron levels determined using MRI shows excellent correlation with that obtained from liver biopsy (2-4).

Correlation between R2 MRI and liver biopsy The solid line is the calibration established by curve fitting to the data. Error bars represent the ±19% uncertainties for biopsy measurement of average LICs. This percentage has been determined by studies of LIC heterogeneity in fibrosis-free livers. The dashed lines show the 95% limits of agreement between R2-LIC and LIC by biopsy. High levels of sensitivity and specificity were observed at various clinically important thresholds. The sensitivity of R2 to biopsy starts to decrease at higher LICs, partly due to the increase in biopsy sampling error at high LICs. This research was originally published in Blood. (St Pierre et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood. 2005;105(2):855-61.) © American Society of Hematology

Evaluation of cardiac iron

MRI remains the only noninvasive modality in clinical use with the ability to detect cardiac iron deposition. T2* MRI is rapidly becoming the new standard for measuring cardiac iron levels.

MRI detection of cardiac iron overload A cardiac T2* MRI image shows myocardial iron stores. The lighter ventricle walls in the left image indicate heavy iron loading. Used with permission from Anderson, et al (2). © 2001 Oxford University Press. MRI detection of cardiac iron overload.

Accuracy of cardiac MRI

One study found that below a myocardial T2* of 20 ms, there was a progressive and significant decline in left ventricular ejection fraction (LVEF) (2). In general, the lower the T2*, the higher the risk of cardiac dysfunction, with a T2* <8 ms suggestive of severe iron overload (2).

Correlation between T2* and cardiac function Myocardial T2* <20 ms was associated with a significant decline in LVEF, suggestive of iron overload-induced cardiac dysfunction. Used with permission from Anderson, et al (2). © 2001 Oxford University Press. MRI detection of cardiac iron overload.

Advantages of MRI

MRI is suitable for ongoing assessment of body iron levels and regular evaluation of therapy. The ability to analyze the whole organ and quantify its iron stores provides at least a theoretical advantage over liver biopsy.

Disadvantages of MRI

Although MRI shows promise as an accurate, noninvasive test for iron overload, variability in its quantitative accuracy currently limits its usefulness as a definitive diagnostic test, especially when non-validated image acquisition protocols are used.