Multicenter Reproducibility of Liver Iron Quantification with 1.5-T and 3.0-T MRI

Abstract

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.

Graphical abstract

Figure 1:

Flowchart and summary of recruitment. JHU = Johns Hopkins University, LIC = liver iron concentration, UTSW = University of Texas Southwestern, UW = University of Wisconsin–Madison.

Figure 2:

Representative R2* and liver iron concentration (LIC) maps. (A) Representative R2* maps from three participants with different levels of iron overload, obtained with MRI systems from three different vendors. For each participant, R2* maps were obtained at both clinical field strengths, 1.5 T and 3.0 T. (B) Corresponding LIC maps obtained by applying the calibration reported herein. Although R2* increases approximately linearly with field strength, R2*-based LIC quantification is independent of field strength. JHU = Johns Hopkins University, UTSW = University of Texas Southwestern, UW = University of Wisconsin–Madison.

Figure 3:

Graphs show R2* liver iron concentration (LIC) calibration for (A) each of the four centers using 1.5 T, (B) each of the three centers using 3.0 T, and (C) the center using 2.89 T. The dashed lines show the 95% CIs for the pooled calibration at 1.5 T and 3.0 T. JHU = Johns Hopkins University, UTSW = University of Texas Southwestern, UW = University of Wisconsin–Madison.

Figure 4:

Receiver operating characteristic curves for R2*-based liver iron concentration (LIC) in the detection of several LIC thresholds. Results are shown pooled across all four centers for each of the two clinical field strengths, (A) 1.5 T and (B) 3.0 T (including both 2.89 T and 3.0 T). AUC = area under the receiver operating characteristic curve.

Figure 5:

Scatterplots of liver R2* measurements across the two field strengths, 1.5 T and 3.0 T, for each of the centers. (A) Plot shows 1.5-T versus 3.0-T R2* measurements for three centers (University of Wisconsin–Madison, University of Texas Southwestern, Stanford). (B) Plot shows 1.5-T versus 2.89-T R2* measurements for one center (Johns Hopkins University).

Figure 6:

Performance of serum ferritin (SF) concentration in the evaluation of liver iron concentration (LIC). (A) Scatterplot with linear regression between serum ferritin concentration and LIC. (B) Receiver operating characteristic curves for several LIC thresholds. The corresponding serum ferritin concentration thresholds determined using the Youden criterion are shown. AUC = area under the receiver operating characteristic curve, thres = threshold.