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Background: Recent multicenter, multivendor MRI-based R2* vs. liver iron concentration (LIC) calibrations (i.e., MCMV calibrations) may facilitate broad clinical dissemination of R2*-based LIC quantification. However, these calibrations are based on a centralized offline R2* reconstruction, and their applicability with vendor-provided R2* maps is unclear., Purpose: To determine R2* ranges of agreement between the centralized and three MRI vendors' R2* reconstructions., Study Type: Prospective., Subjects: Two hundred and seven subjects (mean age 37.6 ± 19.6 years; 117 male) with known or suspected iron overload from four academic medical centers., Field Strength/sequence: Standardized multiecho spoiled gradient echo sequence at 1.5 T and 3.0 T for R2* mapping and a multiple spin-echo sequence at 1.5 T for LIC quantification. MRI vendors: GE Healthcare, Philips Healthcare, and Siemens Healthineers., Assessment: R2* maps were generated using both the centralized and vendor reconstructions, and ranges of agreement were determined. R2*-LIC linear calibrations were determined for each site, field strength, and reconstruction and compared with the MCMV calibrations., Statistical Tests: Bland-Altman analysis to determine ranges of agreement. Linear regression, analysis of covariance F tests, and Tukey's multiple comparison testing to assess reproducibility of calibrations across sites and vendors. A P value <0.05 was considered significant., Results: The upper limits of R2* ranges of agreement were approximately 500, 375, and 330 s -1 for GE, Philips, and Siemens reconstructions, respectively, at 1.5 T and approximately 700 and 800 s -1 for GE and Philips, respectively, at 3.0 T. Within the R2* ranges of agreement, vendor R2*-LIC calibrations demonstrated high reproducibility (no significant differences between slopes or intercepts; P ≥ 0.06) and agreed with the MCMV calibrations (overlapping 95% confidence intervals)., Data Conclusion: Based on the determined upper limits, R2* measurements obtained from vendor-provided R2* maps may be reliably and practically used to quantify LIC less than approximately 8-13 mg/g using the MCMV calibrations and similar acquisition parameters as this study., Evidence Level: 1 TECHNICAL EFFICACY: Stage 3., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background MRI is a standard of care tool to measure liver iron concentration (LIC). Compared with regulatory-approved R2 MRI, R2* MRI has superior speed and is available in most MRI scanners; however, the cross-vendor reproducibility of R2*-based LIC estimation remains unknown. Purpose To evaluate the reproducibility of LIC via single-breath-hold R2* MRI at both 1.5 T and 3.0 T with use of a multicenter, multivendor study. Materials and Methods Four academic medical centers using MRI scanners from three different vendors (three 1.5-T scanners, one 2.89-T scanner, and two 3.0-T scanners) participated in this prospective cross-sectional study. Participants with known or suspected liver iron overload were recruited to undergo multiecho gradient-echo MRI for R2* mapping at 1.5 T and 3.0 T (2.89 T or 3.0 T) on the same day. R2* maps were reconstructed from the multiecho images and analyzed at a single center. Reference LIC measurements were obtained with a commercial R2 MRI method performed using standardized 1.5-T spin-echo imaging. R2*-versus-LIC calibrations were generated across centers and field strengths using linear regression and compared using F tests. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic performance of R2* MRI in the detection of clinically relevant LIC thresholds. Results A total of 207 participants (mean age, 38 years ± 20 [SD]; 117 male participants) were evaluated between March 2015 and September 2019. A linear relationship was confirmed between R2* and LIC. All calibrations within the same field strength were highly reproducible, showing no evidence of statistically significant center-specific differences ( P > .43 across all comparisons). Calibrations for 1.5 T and 3.0 T were generated, as follows: for 1.5 T, LIC (in milligrams per gram [dry weight]) = -0.16 + 2.603 × 10 -2 R2* (in seconds -1 ); for 2.89 T, LIC (in milligrams per gram) = -0.03 + 1.400 × 10 -2 R2* (in seconds -1 ); for 3.0 T, LIC (in milligrams per gram) = -0.03 + 1.349 × 10 -2 R2* (in seconds -1 ). Liver R2* had high diagnostic performance in the detection of clinically relevant LIC thresholds (area under the ROC curve, >0.98). Conclusion R2* MRI enabled accurate and reproducible quantification of liver iron overload over clinically relevant ranges of liver iron concentration (LIC). The data generated in this study provide the necessary calibrations for broad clinical dissemination of R2*-based LIC quantification. ClinicalTrials.gov registration no.: NCT02025543 © RSNA, 2022 Online supplemental material is available for this article.

The aim of this study was to reproduce relaxivity-iron calibration in hepatic iron overload using a Monte Carlo model, and further extend the model with multiple spin echo (MSE) imaging. As previously reported, relationships between relaxation rates ( R 2 * and single spin echo R 2 ) and liver iron concentration (LIC) can be characterized by a Monte Carlo model incorporating realistic liver structure, iron distribution, and proton mobility. In this study, relaxivity-iron calibration curves at 1.5 and 3.0 T were simulated using the Monte Carlo model. Furthermore, the model was extended with MSE imaging, and iron calibrations were evaluated using two different fitting models: mononexponential with a constant offset and nonmonoexponential. Results consistent with previous empirical calibrations and Monte Carlo predictions were accurately reproduced for relaxivity-iron calibration. The predicted R 2 * and single spin echo R 2 increased by a factor of 2.00 and 1.51, respectively, at 1.5 versus 3.0 T. MSE signals and their corresponding R 2 depended strongly on LIC, interecho time, and field strength. Preliminary results showed that a nonmonoexponential model accurately characterizes the simulated MSE signals, and that strong correlations were found between predicted relaxation parameters and LIC. In conclusion, relaxivity-iron calibration is reproducible using the proposed Monte Carlo model. Furthermore, this model can be readily extended to other important applications, including predicting signal behavior for MSE imaging., (© 2021 John Wiley & Sons, Ltd.)

Objectives: To evaluate the reproducibility of liver R2* measurements between a 2D cardiac ECG-gated and a 3D breath-hold liver CSE-MRI acquisition for liver iron quantification., Methods: A total of 54 1.5 T MRI exams from 51 subjects (18 women, 36 men, age 35.2 ± 21.8) were included. These included two sub-studies with 23 clinical MRI exams from 19 patients identified retrospectively, 24 participants with known or suspected iron overload, and 7 healthy volunteers acquired prospectively. The 2D cardiac and the 3D liver R2* maps were acquired in the same exam. Either acquisitions were reconstructed using a complex R2* algorithm that accounts for the presence of fat and residual phase errors due to eddy currents. Data were analyzed using colocalized ROIs in the liver., Results: Linear regression analysis demonstrated high Pearson's correlation and Lin's concordance coefficient for the overall study and both sub-studies. Bland-Altman analysis also showed good agreement, except for a slight increase of the mean R2* value above ~ 400 s -1 . The Kolmogorow-Smirnow test revealed a non-normal distribution for (R2* 3D-R2* 2D) values from 0 to 600 s -1 in contrast to the 0-200 s -1 and 0-400 s -1 subpopulations. Linear regression analysis showed no relevant differences other than the intercept, likely due to only 7 measurements above 400 s -1 ., Conclusions: The results demonstrate that R2*-measurements in the liver are feasible using 2D cardiac R2* maps compared to 3D liver R2* maps as the reference. Liver R2* may be underestimated for R2* > 400 s -1 using the 2D cardiac R2* mapping method., (© 2021. The Author(s).)

Purpose: To design, construct, and evaluate quantitative MR phantoms that mimic MRI signals from the liver with simultaneous control of three parameters: proton-density fat fraction (PDFF), R 2 ∗ , and T 1 . These parameters are established biomarkers of hepatic steatosis, iron overload, and fibrosis/inflammation, respectively, which can occur simultaneously in the liver., Methods: Phantoms including multiple vials were constructed. Peanut oil was used to modulate PDFF, MnCl 2 and iron microspheres were used to modulate R 2 ∗ , and NiCl 2 was used to modulate the T 1 of water (T 1,water ). Phantoms were evaluated at both 1.5 T and 3 T using stimulated-echo acquisition-mode MRS and chemical shift-encoded MRI. Stimulated-echo acquisition-mode MRS data were processed to estimate T 1,water , T 1,fat , R 2 , water ∗ , and R 2 , fat ∗ for each vial. Chemical shift-encoded MRI data were processed to generate PDFF and R 2 ∗ maps, and measurements were obtained in each vial. Measurements were evaluated using linear regression and Bland-Altman analysis., Results: High-quality PDFF and R 2 ∗ maps were obtained with homogeneous values throughout each vial. High correlation was observed between imaging PDFF with target PDFF (slope = 0.94-0.97, R 2 = 0.994-0.997) and imaging R 2 ∗ with target R 2 ∗ (slope = 0.84-0.88, R 2 = 0.935-0.943) at both 1.5 T and 3 T. The values of R 2 , fat ∗ and R 2 , water ∗ were highly correlated with slope close to 1.0 at both 1.5 T (slope = 0.90, R 2 = 0.988) and 3 T (slope = 0.99, R 2 = 0.959), similar to the behavior observed in vivo. The value of T 1,water (500-1200 ms) was controlled with varying NiCl 2 concentration, while T 1,fat (300 ms) was independent of NiCl 2 concentration., Conclusion: Novel quantitative MRI phantoms that mimic the simultaneous presence of fat, iron, and fibrosis in the liver were successfully developed and validated., (© 2020 International Society for Magnetic Resonance in Medicine.)

Objectives: MRI-based R2* mapping may enable reliable and rapid quantification of liver iron concentration (LIC). However, the performance and reproducibility of R2* across acquisition protocols remain unknown. Therefore, the objective of this work was to evaluate the performance and reproducibility of complex confounder-corrected R2* across acquisition protocols, at both 1.5 T and 3.0 T., Methods: In this prospective study, 40 patients with suspected iron overload and 10 healthy controls were recruited with IRB approval and informed written consent and imaged at both 1.5 T and 3.0 T. For each subject, acquisitions included four different R2* mapping protocols at each field strength, and an FDA-approved R2-based method performed at 1.5 T as a reference for LIC. R2* maps were reconstructed from the complex data acquisitions including correction for noise effects and fat signal. For each subject, field strength, and R2* acquisition, R2* measurements were performed in each of the nine liver Couinaud segments and the spleen. R2* measurements were compared across protocols and field strength (1.5 T and 3.0 T), and R2* was calibrated to LIC for each acquisition and field strength., Results: R2* demonstrated high reproducibility across acquisition protocols (p > 0.05 for 96/108 pairwise comparisons across 2 field strengths and 9 liver segments, ICC > 0.91 for each field strength/segment combination) and high predictive ability (AUC > 0.95 for four clinically relevant LIC thresholds). Calibration of R2* to LIC was LIC = - 0.04 + 2.62 × 10 -2 R2* at 1.5 T and LIC = 0.00 + 1.41 × 10 -2 R2* at 3.0 T., Conclusions: Complex confounder-corrected R2* mapping enables LIC quantification with high reproducibility across acquisition protocols, at both 1.5 T and 3.0 T., Key Points: • Confounder-corrected R2* of the liver provides reproducible R2* across acquisition protocols, including different spatial resolutions, echo times, and slice orientations, at both 1.5 T and 3.0 T. • For all acquisition protocols, high correlation with R2-based liver iron concentration (LIC) quantification was observed. • The calibration between confounder-corrected R2* and LIC, at both 1.5 T and 3.0 T, is determined in this study.

Purpose: Determine the impact of the microscopic spatial distribution of iron on relaxometry and susceptibility-based estimates of iron concentration., Methods: Monte Carlo simulations and in vitro experiments of erythrocytes were used to create different microscopic distributions of iron. Measuring iron with intact erythrocyte cells created a heterogeneous distribution of iron, whereas lysing erythrocytes was used to create a homogeneous distribution of iron. Multi-echo spin echo and spoiled gradient echo acquisitions were then used to estimate relaxation parameters ( R 2 and R 2 * ) and susceptibility., Results: Simulations demonstrate that R 2 and R 2 * measurements depend on the spatial distribution of iron even for the same iron concentration and volume susceptibility. Similarly, in vitro experiments demonstrate that R 2 and R 2 * measurements depend on the microscopic spatial distribution of iron whereas the quantitative susceptibility mapping (QSM) susceptibility estimates reflect iron concentration without sensitivity to spatial distribution., Conclusions: R 2 and R 2 * for iron quantification depend on the spatial distribution or iron. QSM-based estimation of iron concentration is insensitive to the microscopic spatial distribution of iron, potentially providing a distribution independent measure of iron concentration., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: To assess the reproducibility of biexponential R 2 -relaxometry MRI for estimation of liver iron concentration (LIC) between proprietary and nonproprietary analysis methods., Methods: This single-center retrospective study, approved by investigational review board and compliant with the Health Insurance Portability and Accountability Act, included 40 liver MRI exams in 38 subjects with suspected or known iron overload. From spin-echo images of the liver, acquired at 5 different echo times (TE = 6-18 ms), biexponential R 2 maps were calculated using 1 proprietary (FerriScan, Resonance Health Ltd., Claremont WA, Australia) and 3 nonproprietary (simulated annealing, nonlinear least squares, dictionary search) analysis methods. Each subject's average liver R 2 value was converted to LIC using a previously validated calibration curve. Inter-method reproducibility for liver R 2 and LIC were assessed for linearity using linear regression analysis and absolute agreement using intraclass correlation and Bland-Altman analysis. For point estimates, 95% confidence intervals were calculated; P values < 0.05 were considered statistically significant., Results: Linearity between the proprietary and nonproprietary methods was excellent across the observed range for R 2 (20-312 s -1 ) and LIC (0.4-52.2 mg/g), with all coefficients of determination (R 2 ) ≥ 0.95. No statistically significant bias was found (slope estimates ∼ 1; intercept estimates ∼ 0; P values > 0.05). Agreement between the 4 methods was excellent for both liver R 2 and LIC (intraclass correlations ≥ 0.97). Bland-Altman 95% limits of agreement in % difference between the proprietary and nonproprietary methods were ≤ 9% and ≤ 16% for R 2 and LIC, respectively., Conclusion: Biexponential R 2 -relaxometry MRI for LIC estimation is reproducible between proprietary and nonproprietary analysis methods., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: We aimed to determine the agreement between quantitative susceptibility mapping (QSM)-based biomagnetic liver susceptometry (BLS) and confounder-corrected R2* mapping with superconducting quantum interference device (SQUID)-based biomagnetic liver susceptometry in patients with liver iron overload., Methods: Data were acquired from two healthy controls and 22 patients undergoing MRI and SQUID-BLS as part of routine monitoring for iron overload. Magnetic resonance imaging was performed on a 3T system using a three-dimensional multi-echo gradient-echo acquisition. Both magnetic susceptibility and R2* of the liver were estimated from this acquisition. Linear regression was used to compare estimates of QSM-BLS and R2* to SQUID-BLS., Results: Both QSM-BLS and confounder-corrected R2* were sensitive to the presence of iron in the liver. Linear regression between QSM-BLS and SQUID-BLS demonstrated the following relationship: QSM-BLS = (-0.22 ± 0.11) + (0.49 ± 0.05) · SQUID-BLS with r 2  = 0.88. The coefficient of determination between liver R2* and SQUID-BLS was also r 2  = 0.88., Conclusion: We determined a strong correlation between both QSM-BLS and confounder-corrected R2* to SQUID-BLS. This study demonstrates the feasibility of QSM-BLS and confounder-corrected R2* for assessing liver iron overload, particularly when SQUID systems are not accessible. Magn Reson Med 78:264-270, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

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., (© 2014 Wiley Periodicals, Inc.)

Purpose: MR-based quantification of liver magnetic susceptibility may enable field strength-independent measurement of liver iron concentration (LIC). However, susceptibility quantification is challenging, due to nonlocal effects of susceptibility on the B0 field. The purpose of this work is to demonstrate feasibility of susceptibility-based LIC quantification using a fat-referenced approach., Methods: Phantoms consisting of vials with increasing iron concentrations immersed between oil/water layers, and 27 subjects (9 controls/18 subjects with liver iron overload) were scanned. Ferriscan (1.5 T) provided R2-based reference LIC. Multiecho three-dimensional-SPGR (1.5 T/3 T) enabled fat-water, B0- and R2*-mapping. Phantom iron concentration (mg Fe L(-1)) was estimated from B0 differences (ΔB0) between vials and neighboring oil. Liver susceptibility and LIC (mg Fe g(-1) dry tissue) was estimated from ΔB0 between the lateral right lobe of the liver and adjacent subcutaneous adipose tissue., Results: Estimated phantom iron concentrations had good correlation with true iron concentrations (1.5 T:slope = 0.86, intercept = 0.72, r(2) = 0.98; 3 T:slope = 0.85, intercept = 1.73, r(2) = 0.98). In liver, ΔB0 correlated strongly with R2* (1.5 T:r(2) = 0.86; 3 T:r(2) = 0.93) and B0-LIC had good agreement with Ferriscan-LIC (slopes/intercepts nearly 1.0/0.0, 1.5 T:r(2) = 0.67, slope = 0.93 ± 0.13, P ≈ 0.50, intercept = 1.93 ± 0.78, P ≈ 0.02; 3 T:r(2) = 0.84, slope = 1.01 ± 0.09, P ≈ 0.90, intercept = 0.23 ± 0.52, P ≈ 0.68)., Discussion: Fat-referenced, susceptibility-based LIC estimation is feasible at both field strengths. This approach may enable improved susceptibility mapping in the abdomen., (Copyright © 2013 Wiley Periodicals, Inc.)

Objectives: To investigate the reliability of diffusion-weighted magnetic resonance imaging (DW-MRI) for staging liver fibrosis in the presence of fat and iron., Methods: Ninety-five patients, including 48 men and 47 women, aged 57.0 ± 14.2 years, underwent liver biopsy. Ninety-six samples were histologically staged for liver fibrosis (0-Ishak score 0; 1-Ishak score 1-4; 2-Ishak score 5-6) and semiquantitatively graded for hepatic iron (0, no; 1, low; 2, moderate; 3, high iron) and for hepatic steatosis. Within 72 h after biopsy, navigator-triggered DW-MRI using b-values of 50/400/800 s/mm(2) was performed in a 1.5-T system, and apparent diffusion coefficients (ADC) were analysed. ADCs were correlated with fibrosis stage, steatosis grade, and iron grade using linear regression., Results: ADC did not correlate with fibrosis stages in either the overall group (n = 96; R (2) = 0.38; P = 0.17) or in the subgroup without liver iron and steatosis (n = 40; R (2) = 0.01; P = 0.75). ADC decreased significantly with steatosis grade in cases without iron and fibrosis (n = 42; R (2) = 0.28; ß = -5.3; P < 0.001). Liver iron was modestly correlated with ADC in patients without fibrosis and steatosis (n = 33; R (2) = 0.29; P = 0.04), whereas high iron concentrations were associated with low ADC values (group 3: β = -489; P = 0.005; reference:group 0) but intermediate levels were not (group 1/group 2: P = 0.93/P = 0.54; reference group: 0)., Conclusions: ADC values are confounded by fat and iron. However, even in patients without fat or iron, DW-MRI does not adequately discriminate the stage of fibrosis., Key Points: • Diffusion-weighted magnetic resonance imaging (DW-MRI) is increasingly used to evaluate liver disease. • DWI using b-values of 50/400/800 s/mm (2) does not adequately quantify fibrosis. • Assessment of the apparent diffusion coefficient (ADC) is confounded by fat and iron. • Fat may influence ADCs by altering water diffusion. • Iron may influence ADCs by signal decay and noise floor effects.