Elsevier

The Lancet

Volume 363, Issue 9406, 31 January 2004, Pages 357-362
The Lancet

Articles
Non-invasive assessment of hepatic iron stores by MRI

https://doi.org/10.1016/S0140-6736(04)15436-6Get rights and content

Summary

Background

MRI has been proposed for non-invasive detection and quantification of liver iron content, but has not been validated as a reproducible and sensitive method, especially in patients with mild iron overload. We aimed to assess the accuracy of a simple, rapid, and easy to implement MRI procedure to detect and quantify hepatic iron stores.

Methods

Of 191 patients recruited, 17 were excluded and 174 studied, 139 in a study group and 35 in a validation group. All patients underwent both percutaneous liver biopsy with biochemical assessment of hepatic iron concentration (B-HIC) and MRI of the liver with various gradient-recalled-echo (GRE) sequences obtained with a 1Β·5 T magnet. Correlation between liver to muscle (L/M) signal intensity ratio and liver iron concentration was calculated. An algorithm to calculate magnetic resonance hepatic iron concentration (MR-HIC) was developed with data from the study group and then applied to the validation group.

Findings

A highly T2-weighted GRE sequence was most sensitive, with 89% sensitivity and 80% specificity in the validation group, with an L/M ratio below 0Β·88. This threshold allowed us to detect all clinically relevant liver iron overload greater than 60 ΞΌmol/g (normal value <36 ΞΌmol/g). With other sequences, an L/M ratio less than 1 was highly specific (>87%) for raised hepatic iron concentration. With respect to B-HIC range analysed (3–375 ΞΌmol/g), mean difference and 95% CI between B-HIC and MR-HIC were quite similar for study and validation groups (0Β·8 ΞΌmol/g [–6Β·3 to 7Β·9] and –2Β·1 ΞΌmol/g [–12Β·9 to 8Β·9], respectively).

Interpretation

MRI is a rapid, non-invasive, and cost effective technique that could limit use of liver biopsy to assess liver iron content. Our MR-HIC algorithm is designed to be used on various magnetic resonance machines.

Introduction

Iron excess, even when mild, is increasingly regarded as an important cofactor in the morbidity attributed to many disorders, including cancer,1 cardiovascular diseases,2 arthritis,3 chronic liver disease,4 and various states characterised by insulin resistance.5 These putative widespread effects of iron probably account for why more and more patients are presently referred to hepatology and haematology clinics for assessment of body iron stores and discussion of iron removal by phlebotomy.6 Assessment of body iron stores by measurement of serum ferritin concentrations has poor specificity.7 The most reliable method to calculate body iron stores is histochemical or biochemical assessment of iron in a liver biopsy specimen.8

Because liver biopsy is an invasive procedure that should be restricted to management of liver disease, attempts have been made to use imaging to detect and quantify hepatic iron content. However, iron deposition is not detectable at ultrasound examination, hyperdensity on CT scan is not specific for iron and can be masked by associated steatosis,9, 10 and the SQUID (superconducting quantum interference) device is not in widespread use.11 Because of the paramagnetic properties of iron, magnetic resonance signal diminishes in liver as iron concentration increases. Gradient-recalled-echo (GRE) techniquesβ€”more sensitive to field inhomogeneities induced by paramagnetic substances than spin-echo sequencesβ€”have been suggested to quantify liver iron excess.12, 13, 14 This sensitivity makes MRI the most accurate routine imaging procedure to assess hepatic iron content, but, surprisingly, the technique is rarely used in management of patients with suspected iron overload, which is probably attributable to an absence of multicentric studies assessing reproducibility of MRI in this setting.

We aimed to assess the accuracy of a simple, rapid, and easy to implement MRI procedure in detection and quantification of hepatic iron stores, especially in patients with slight iron overload.

Section snippets

Patients

During a 32-month period (March 1996, to October, 1998), all patients who were referred to two of us (YD or DG) and were scheduled to undergo liver biopsy at the Liver Unit, Rennes, France, for either suspicion of hepatic iron overload or management of chronic hepatitis C, were asked to undergo MRI for assessment of hepatic iron stores and offered biochemical determination of hepatic iron concentration from their liver biopsy specimen. These patients formed the study group. We did an identical

Results

149 patients were enrolled into the study group and 42 into the validation group. Mean time between liver biopsy and MRI examination was 8Β·2 days (SD 23; range 0–194). No patient had phlebotomy or abnormal bleeding between liver biopsy and MRI. Total facility time per patient was about 15 min, including turnover time between patients. B-HIC and MR-HIC were not assessable in 11 and six patients, respectively, because of biopsy failure (n=1), small size of biopsy sample (n=10), metallic implants

Discussion

We have shown that MRI with GRE sequences on a 1Β·5 T magnet is a non-invasive alternative method for assessment of liver iron overload and quantification of hepatic iron concentration, from 60 ΞΌmol/g to about ten times the upper limit of normal (375 ΞΌmol/g).

Liver iron overload leads to a decline in liver magnetic resonance signal because of T2-shortening related to the paramagnetic properties of iron stored within the liver.18 Unfortunately, magnetic resonance signal is dependent on multiple

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