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Objective: To validate the proton density fat fraction (PDFF) obtained by the MRQuantif software from 2D chemical shift encoded MR (CSE-MR) data in comparison with the histological steatosis data., Methods: This study, pooling data from 3 prospective studies spread over time between January 2007 and July 2020, analyzed 445 patients who underwent 2D CSE-MR and liver biopsy. MR derived liver iron concentration (MR-LIC) and PDFF was calculated using the MRQuantif software. The histological standard steatosis score (SS) served as reference. In order to get a value more comparable to PDFF, histomorphometry fat fraction (HFF) were centrally determined for 281 patients. Spearman correlation and the Bland and Altman method were used for comparison., Results: Strong correlations were found between PDFF and SS (r s  = 0.84, p < 0.001) or HFF (r s  = 0.87, p < 0.001). Spearman's coefficients increased to 0.88 (n = 324) and 0.94 (n = 202) when selecting only the patients without liver iron overload. The Bland and Altman analysis between PDFF and HFF found a mean bias of 5.4% ± 5.7 [95% CI 4.7, 6.1]. The mean bias was 4.7% ± 3.7 [95% CI 4.2, 5.3] and 7.1% ± 8.8 [95% CI 5.2, 9.0] for the patients without and with liver iron overload, respectively., Conclusion: The PDFF obtained by MRQuantif from a 2D CSE-MR sequence is highly correlated with the steatosis score and very close to the fat fraction estimated by histomorphometry. Liver iron overload reduced the performance of steatosis quantification and joint quantification is recommended. This device-independent method can be particularly useful for multicenter studies., Clinical Relevance Statement: The quantification of liver steatosis using a vendor-neutral 2D chemical-shift MR sequence, processed by MRQuantif, is well correlated to steatosis score and histomorphometric fat fraction obtained from biopsy, whatever the magnetic field and the MR device used., Key Points: • The PDFF measured by MRQuantif from 2D CSE-MR sequence data is highly correlated to hepatic steatosis. • Steatosis quantification performance is reduced in case of significant hepatic iron overload. • This vendor-neutral method may allow consistent estimation of PDFF in multicenter studies., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Accumulation of excess iron in the body, or systemic iron overload, results from a variety of causes. The concentration of iron in the liver is linearly related to the total body iron stores and, for this reason, quantification of liver iron concentration (LIC) is widely regarded as the best surrogate to assess total body iron. Historically assessed using biopsy, there is a clear need for noninvasive quantitative imaging biomarkers of LIC. MRI is highly sensitive to the presence of tissue iron and has been increasingly adopted as a noninvasive alternative to biopsy for detection, severity grading, and treatment monitoring in patients with known or suspected iron overload. Multiple MRI strategies have been developed in the past 2 decades, based on both gradient-echo and spin-echo imaging, including signal intensity ratio and relaxometry strategies. However, there is a general lack of consensus regarding the appropriate use of these methods. The overall goal of this article is to summarize the current state of the art in the clinical use of MRI to quantify liver iron content and to assess the overall level of evidence of these various methods. Based on this summary, expert consensus panel recommendations on best practices for MRI-based quantification of liver iron are provided., (© RSNA, 2023.)

Iron overload is a severe general complication of hereditary anemias. Treatment with iron chelators is hampered by important side-effects, high costs, and the lack of availability in many countries with a high prevalence of hereditary anemias. In this phase III randomized placebo-controlled trial, we assigned adults with non-transfusion-dependent hereditary anemias with mild-to-moderate iron overload to receive esomeprazole (at a dose of 40 mg twice daily) or placebo for 12 months in a cross-over design. The primary end point was change of liver iron content measured by MRI. A total of 30 participants were enrolled in the trial. Treatment with esomeprazole resulted in a statistically significant reduction in liver iron content that was 0.55 mg Fe/g dw larger than after treatment with placebo (95%CI [0.05 to 1.06]; p = 0.03). Median baseline liver iron content at the start of esomeprazole was 4.99 versus 4.49 mg Fe/g dw at start of placebo. Mean delta liver iron content after esomeprazole treatment was -0.57 (SD 1.20) versus -0.11 mg Fe/g dw (SD 0.75) after placebo treatment. Esomeprazole was well tolerated, reported adverse events were mild and none of the patients withdrew from the study due to side effects. In summary, esomeprazole resulted in a significant reduction in liver iron content when compared to placebo in a heterogeneous group of patients with non-transfusion-dependent hereditary anemias. From an international perspective this result can have major implications given the fact that proton pump inhibitors may frequently be the only realistic therapy for many patients without access to or not tolerating iron chelators., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Our intention is to demystify the MR quantification of hepatic iron (i.e., the liver iron concentration) and give you a step-by-step approach by answering the most pertinent questions. The following article should be more of a manual or guide for every radiologist than a classic review article, which just summarizes the literature. Furthermore, we provide important background information for professional communication with clinicians. The information regarding the physical background is reduced to a minimum. After reading this article, you should be able to perform adequate MR measurements of the LIC with 1.5-T or 3.0-T scanners. KEY POINTS: • MRI is widely accepted as the primary approach to non-invasively determine liver iron concentration (LIC). • This article is a guide for every radiologist to perform adequate MR measurements of the LIC. • When using R2* relaxometry, some points have to be considered to obtain correct measurements-all explained in this article.

Objectives: To evaluate the performance and limitations of the R2* and signal intensity ratio (SIR) methods for quantifying liver iron concentration (LIC) at 3 T., Methods: A total of 105 patients who underwent a liver biopsy with biochemical LIC (LIC b ) were included prospectively. All patients underwent a 3-T MRI scan with a breath-hold multiple-echo gradient-echo sequence (mGRE). LIC calculated by 3-T SIR algorithm (LIC SIR ) and by R2* (LIC R2* ) were correlated with LIC b . Sensitivity and specificity were calculated. The comparison of methods was analysed for successive classes., Results: LIC b was strongly correlated with R2* (r = 0.95, p < 0.001) and LIC SIR (r = 0.92, p < 0.001). In comparison to LIC b , LIC R2* and LIC SIR detect liver iron overload with a sensitivity/specificity of 0.96/0.93 and 0.92/0.95, respectively, and a bias ± SD of 7.6 ± 73.4 and 14.8 ± 37.6 μmol/g, respectively. LIC R2* presented the lowest differences for patients with LIC b values under 130 μmol/g. Above this value, LIC SIR has the lowest differences., Conclusions: At 3 T, R2* provides precise LIC quantification for lower overload but the SIR method is recommended to overcome R2* limitations in higher overload. Our software, available at www.mrquantif.org , uses both methods jointly and selects the best one., Key Points: • Liver iron can be accurately quantified by MRI at 3 T • At 3 T, R2* provides precise quantification of slight liver iron overload • At 3 T, SIR method is recommended in case of high iron overload • Slight liver iron overload present in metabolic syndrome can be depicted • Treatment can be monitored with great confidence.

MRI is now the reference method for detecting and quantifying hepatic and extrahepatic iron overload, regardless of its cause. The decrease of the hepatic signal is proportional to the amount of iron in the tissues. It is more pronounced with T2*-weighted gradient echo sequences. It increases proportionally with the strength of the magnetic field. Thus a 3-T MRI is be more sensitive and probably more accurate to detect a slight iron overload, as seen in dysmetabolic hepatosiderosis. Conversely, a 1.5-T MRI better estimates a high overload. Quantification can be done with the calculation of T2* (or R2*) or by using the liver to muscle signal intensity ratio (SIR). Today with a single multi-echo gradient-echo sequence, obtained in a unique apnea, the two methods can be used simultaneously. An associated quantification of steatosis is also obtained. This same type of sequence is proposed for quantification of iron in other tissues and in particular for the myocardium., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate the performance and limitations of the signal intensity ratio method for quantifying liver iron overload at 3 T., Methods: Institutional review board approval and written informed consent from all participants were obtained. One hundred and five patients were included prospectively. All patients underwent a liver biopsy with biochemical assessment of hepatic iron concentration and a 3 T MRI scan with 5 breath-hold single-echo gradient-echo sequences. Linear correlation between liver-to-muscle signal intensity ratio and liver iron concentration was calculated. The algorithm for calculating magnetic resonance hepatic iron concentration was adapted from the method described by Gandon et al. with echo times divided by 2. Sensitivity and specificity were calculated., Results: Five patients were excluded (coil selection failure or missing sequence) and 100 patients were analyzed, 64 men and 36 women, 52 ± 13.3 years old, with a biochemical hepatic iron concentration range of 0-630 µmol/g. Linear correlation between biochemical hepatic iron concentration and MR-hepatic iron concentration was excellent with a correlation coefficient = 0.96, p < 0.0001. Sensitivity and specificity were, respectively, 83% (0.70-0.92) and 96% (0.85-0.99), with a pathological threshold of 36 µmol/g., Conclusion: Signal intensity ratio method for quantifying liver iron overload can be used at 3 T with echo times divided by 2.

Purpose: To quantify hepatic and splenic iron load, which is a critical issue for iron overload disease diagnosis. MRI is useful to noninvasively determine liver iron concentration, but not proven to be adequate for robust evaluation of splenic iron load. We evaluated the usefulness of MRI-derived parameters to determine splenic iron concentration in mice., Materials and Methods: A mouse model of experimental iron load was used. Multi-echo spin-echo images of liver and spleen were acquired at 4.7 Tesla. The parameters were tested at all echoes with and without an external reference. Splenic and hepatic iron concentrations were determined using biochemical assay as the gold standard., Results: Our results show that (i) use of an internal or external reference is essential; (ii) optimal echo times were TE = 19.5 ms and TE = 32.5 ms for the liver and spleen, respectively; (iii) in the liver, the relationship between biochemical and MRI iron concentration determinations is logarithmic; (iv) in the spleen, the best relationship is an inverse function., Conclusion: A single spin-echo sequence allows robust estimation of hepatic and splenic iron content. Parameters classically used for hepatic iron concentration cannot be applied to splenic iron determination, which requires both the specific sequence and the adapted fitting function.

Hepatic iron overload conditions can be classified as genetic, mainly related to HFE haemochromatosis, and secondary, mainly associated with haematological and hepatic disorders and with metabolic syndrome. The strict affirmation of iron excess relies upon liver biopsy, MRI or calculation of the amount of iron removed through phlebotomies. Determination of its cause relies upon the assessment of transferrin saturation which, when increased, suggests the diagnosis of either haemochromatosis--implying HFE testing--or overload secondary to dysmyelopoiesis or to end-stage cirrhosis, and, when normal, suggests the diagnosis of dysmetabolic iron overload syndrome.

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 1.5 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 0.88. This threshold allowed us to detect all clinically relevant liver iron overload greater than 60 micromol/g (normal value <36 micromol/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 micromol/g), mean difference and 95% CI between B-HIC and MR-HIC were quite similar for study and validation groups (0.8 micromol/g [-6.3 to 7.9] and -2.1 micromol/g [-12.9 to 8.9], 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.

Aceruloplasminemia is an autosomal recessive disease of iron overload associated with mutation(s) in the ceruloplasmin gene. We report here a new case of aceruloplasminemia in a woman who is a compound heterozygote for two new mutations. Besides this novel genotypic profile, this observation provides new insights on: (i) iron metabolism with normal erythroid repartition, in the absence of serum non-transferrin-bound iron and with an increase of 59Fe plasma clearance; (ii) hepatic abnormalities associated with the presence of iron-free foci; (iii) the therapeutic management of the disease, chronic subcutaneous infusion of deferrioxamine being remarkably effective at reducing hepatic iron overload.

Iron overload involves primarily hepatocytes in case of digestive hyperabsorption (hemochromatosis and dyserythropoiesis) and macrophages in case of transfusional excess. Serum iron and transferrin saturation are poorly correlated with the degree of iron overload. Serum ferritin is a better reflect of iron stores but numerous clinical conditions, unrelated to variations of iron load, can increase the serum level. Biochemical determination of liver iron overload is the gold standard of iron quantification and well correlated to the level of iron burden appreciated by the amount of iron removed by venesection, but its determination necessitates a liver biopsy and is dependant of sampling error in case of heterogeneous iron deposits (cirrhosis). The sensitivity of computed tomography is insufficient, beeing unable to detect iron overload below 5 times the normal liver iron load, especially in case of associated steatosis. Magnetic resonance imaging is a valuable tool when using T2 weighted gradient echo sequences on 1.5 Tesla magnet and permits non invasive iron overload quantification.