Quantification of liver iron with MRI: state of the art and remaining challenges

Abstract

Liver iron overload is the histological hallmark of hereditary hemochromatosis and transfusional hemosiderosis, and can also occur in chronic hepatopathies. Iron overload can result in liver damage, with the eventual development of cirrhosis, liver failure, and hepatocellular carcinoma. Assessment of liver iron levels is necessary for detection and quantitative staging of iron overload and monitoring of iron-reducing treatments. This article discusses the need for noninvasive assessment of liver iron and reviews qualitative and quantitative methods with a particular emphasis on magnetic resonance imaging (MRI). Specific MRI methods for liver iron quantification include signal intensity ratio as well as R2 and R2* relaxometry techniques. Methods that are in clinical use, as well as their limitations, are described. Remaining challenges, unsolved problems, and emerging techniques to provide improved characterization of liver iron deposition are discussed.

Keywords: MR relaxometry; R2; R2*; liver iron; susceptometry.

Figure 1

Representative CT images in patients with liver iron overload. MRI-based R2* (=1/T2*) maps also shown for comparison.

Figure 2

T2- or T2*-weighted images enable qualitative assessment of liver iron. Images show representative T2- and T2*-weighted images in patients with different levels of iron overload. T2-weighted images were obtained using a 2D single spin echo sequence (TE=12ms). T2*-weighted images were obtained with a single breath-hold 3D SPGR sequence (TE=5.2ms).

Figure 3

OP/IP imaging is confounded by the simultaneous presence of fat and iron. In this example, OP/IP images from a patient with severe steatosis and moderately elevated R2* only indicate mild steatosis. However, joint estimation of fat-fraction and R2* using a six-echo acquisition demonstrates a fat-fraction of 28% and R2* of 90 s⁻¹. The presence of fat and iron was confirmed by biopsy (bottom images).

Figure 4

Outline of the R2 (=1/T2) mapping process. In this technique, several spin-echo images are acquired with increasing echo times. Images are subsequently processed to estimate the R2 relaxation rate at each voxel. Examples show R2 maps from a normal volunteer without iron overload (top), and from a patient with iron overload (bottom).

Figure 5

Relationship between relaxation rates R2 and R2*, and biopsy-determined liver iron concentration, as measured by St. Pierre et al, and by Wood et al, respectively.

Figure 6

R2 can be measured from spectroscopy acquisitions in order to assess liver iron levels. Similar to imaging-based R2 mapping techniques, STEAM or PRESS spectra can be acquired at increasing echo times, and the rate of decay of the signal with echo time can be measured. Importantly, multi-echo spectra can be acquired quickly and with good SNR. However, they do not provide information on the spatial distribution of iron.

Figure 7

Outline of the R2* (=1/T2*) mapping process. In this technique, several gradient-echo images are acquired with increasing echo times. Images are subsequently processed to estimate the R2* relaxation rate at each voxel. Examples show R2* maps from a normal volunteer without iron overload (top), and from a patient with iron overload (bottom).

Figure 8

R2* relaxometry can be used to monitor treatment for iron overload. Images show R2* maps from a 21 year old patient undergoing chelation therapy. Note the sharp decrease in R2* after one year of therapy.

Figure 9

Effects of noise (A–B) and fat (C–D) on R2* estimation. (A–B) R2* fitting in the presence of noise, in high R2* case (R2*=500 /s) (Adapted from Ref (83)). (A) Noise in complex MRI signals is zero-mean. Complex fitting provides unbiased R2* measurements over a wide range of R2* values. (B) Noisy magnitude signals results in a “noise floor” at low SNR, leading to underestimation of R2* when using magnitude fitting. (C) The presence of fat introduces additional oscillations in the MR signal, as fat and water become in and out of phase. (D) Measured R2* from 6-TE echo trains (fat-fraction=40%, R2*=30 /s), using TEinit=1ms and varying dTE. Fat-water oscillations result in severe errors in fat-uncorrected R2* measurements. Note that errors occur even when the echo spacing is equal to 4.61ms (ie: one cycle of the main fat peak around the water resonance), due to the spectral complexity of the fat signal.

Figure 10

Different mechanisms for iron overload lead to distinct organ involvement, as depicted with R2* mapping. Note the similar liver R2* but different spleen R2* in a patient with hereditary hemochromatosis and a patient with transfusional hemosiderosis.

Figure 11

Imaging-based techniques for liver iron assessment may be important in cases of heterogeneous iron deposition. Images show R2* maps from two patients with heterogeneous iron overload. In these patients, localized techniques such as biopsy or MR spectroscopy may not provide a representative measurement of liver iron.

Figure 12

The presence of liver iron modifies the susceptibility of tissue, which in turn modifies the B0 field map measured with MRI. Similar to the principle of SQUID biosusceptometry, MRI-based B0 field mapping may be able to detect and quantify susceptibility changes caused by the presence of iron in the liver and other organs. Images show R2* maps and B0 field maps in a normal volunteer without iron overload, and in a patient with iron overload.