Liver Iron Quantification with MR Imaging: A Primer for Radiologists

Abstract

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 (predominantly caused by β-thalassemia major and sickle cell disease) 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. Liver biopsy was the historical reference standard for detection and quantification of liver iron content. Magnetic resonance (MR) imaging is now commonly used for liver iron quantification, including assessment of distribution, detection, grading, and monitoring of treatment response in iron overload. Several MR imaging techniques have been developed for iron quantification, each with advantages and limitations. The liver-to-muscle signal intensity ratio technique is simple and widely available; however, it assumes that the reference tissue is normal. Transverse magnetization (also known as R2) relaxometry is validated but is prone to respiratory motion artifacts due to a long acquisition time, is presently available only for 1.5-T imaging, and requires additional cost and delay for off-line analysis. The R2* technique has fast acquisition time, demonstrates a wide range of liver iron content, and is available for 1.5-T and 3.0-T imaging but requires additional postprocessing software. Quantitative susceptibility mapping has the highest sensitivity for detecting iron deposition; however, it is still investigational, and the correlation with liver iron content is not yet established. RSNA, 2018.

Hepatic R2* is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease

“…Estimates of PDFF were similar between field strengths, but R2* values were generally higher at 3T. The mean liver R2* value was 37.2 ± 6.8 s −1 at 1.5T and 59.8 ± 12.9 s −1 at 3T, and R2* values were generally in the normal range (<60 s −1 at 1.5T, <126 at 3T) . The distributions of baseline PDFF and R2* values are summarized in Fig.…”

“…One of the reasons this study is clinically relevant is that in patients with NAFLD, liver iron deposition may portend worse clinical outcomes . Since MRI‐based measures such as R2* estimation have all but replaced liver biopsy for assessment of liver iron concentration in other populations, investigators logically may attempt to use measurements of R2* to quantify liver iron in patients with NAFLD . However, our data show that hepatic steatosis, as quantified by PDFF, substantially confounds R2* measurements in this population.…”

Biexponential R2* relaxometry for estimation of liver iron concentration in children: A better fit for high liver iron states

“…Our goal was to remain consistent with the original methodology described by Wood et al Finally, our sample only included participants with transfusional hemosiderosis. Patients with hemochromatosis, a nontransfusional hemosiderosis, exhibit a different LIC distribution compared with conditions such as beta‐thalassemia and sickle cell disease …”

“…The first large study validating R2* relaxometry showed that the R2* calibration curve with liver biopsy was linear . R2* has many advantages over other MRI iron quantification techniques, such as fast acquisition time, wider detection range of liver iron content, and more robust results for tracking chelation response after short treatment periods . However, R2* relaxometry's capacity to calculate liver iron concentration (LIC) is limited in patients with severe iron overload .…”

“…4 R2* has many advantages over other MRI iron quantification techniques, such as fast acquisition time, wider detection range of liver iron content, and more robust results for tracking chelation response after short treatment periods. 5,6 However, R2* relaxometry's capacity to calculate liver iron concentration (LIC) is limited in patients with severe iron overload. 7 The concentration of hemosiderin-a long-term iron-storage molecule-increases with severe iron overload states and exhibits a non-monoexponential signal decay that renders R2* analysis inadequate with current techniques.…”