Multicenter validation of spin‐density projection‐assisted R2‐MRI for the noninvasive measurement of liver iron concentration

Abstract

PurposeMagnetic resonance imaging (MRI)-based techniques for assessing liver iron concentration (LIC) have been limited by single scanner calibration against biopsy. Here, the calibration of spin-density projection-assisted (SDPA) R2-MRI (FerriScan®) in iron-overloaded β-thalassemia patients treated with the iron chelator, deferasirox, for 12 months is validated.MethodsSDPA R2-MRI measurements and percutaneous needle liver biopsy samples were obtained from a subgroup of patients (n = 233) from the ESCALATOR trial. Five different makes and models of scanner were used in the study.ResultsLIC, derived from mean of MRI- and biopsy-derived values, ranged from 0.7 to 50.1 mg Fe/g dry weight. Mean fractional differences between SDPA R2-MRI- and biopsy-measured LIC were not significantly different from zero. They were also not significantly different from zero when categorized for each of the Ishak stages of fibrosis and grades of necroinflammation, for subjects aged 3 to <8 versus ≥8 years, or for each scanner model. Upper and lower 95% limits of agreement between SDPA R2-MRI and biopsy LIC measurements were 74 and −71%.ConclusionThe calibration curve appears independent of scanner type, patient age, stage of liver fibrosis, grade of necroinflammation, and use of deferasirox chelation therapy, confirming the clinical usefulness of SDPA R2-MRI for monitoring iron overload. Magn Reson Med 71:2215–2223, 2014. © 2013 Wiley Periodicals, Inc.

R2 and R2* are equally effective in evaluating chronic response to iron chelation

“…Ferriscan was originally validated to liver biopsy in 105 subjects [4], and the calibration reaffirmed in a subsequent test sample of 233 subjects [5]. Limits of agreement in the first study were [256%, 50%] and [271%, 74%] in the second study [5].…”

“…Ferriscan was originally validated to liver biopsy in 105 subjects [4], and the calibration reaffirmed in a subsequent test sample of 233 subjects [5]. Limits of agreement in the first study were [256%, 50%] and [271%, 74%] in the second study [5]. No systematic differences were observed with respect to fibrosis or necroinflammatory stage, but random differences between liver iron concentration (LIC) by R2 and LIC by biopsy increased with liver fibrosis stage [5].…”

Reference method for measurement of the hepatic iron concentration

“…The systematic review emphasized the low quality of existing studies "both at the conduct and reporting levels" and the paucity of available evidence [13], even for the protocol approved by the U.S. Food and Drug Administration (FerriScan; Resonance Health, Claremont, Australia). Other recent commentaries have emphasized that studies using T 2 , R 2 , T 2 *, and R 2 * MRI parameters typically have been calibrated against chemical measurements of hepatic iron in biopsy samples by using only a single scanner and cautioned that such calibrations are not transferable [15]. Depending on the calibration used, a liver T 2 * of 2.5 ms measured on a 1.5-T scanner corresponds to a hepatic iron concentration ranging from 5.4 mg Fe/g dry weight [16] (<7.0 mg Fe/g dry weight; low risk of complications) [17] to 26.4 mg Fe/g dry weight [18] (>15.0 mg Fe/g dry weight; high risk) [15].…”

“…Other recent commentaries have emphasized that studies using T 2 , R 2 , T 2 *, and R 2 * MRI parameters typically have been calibrated against chemical measurements of hepatic iron in biopsy samples by using only a single scanner and cautioned that such calibrations are not transferable [15]. Depending on the calibration used, a liver T 2 * of 2.5 ms measured on a 1.5-T scanner corresponds to a hepatic iron concentration ranging from 5.4 mg Fe/g dry weight [16] (<7.0 mg Fe/g dry weight; low risk of complications) [17] to 26.4 mg Fe/g dry weight [18] (>15.0 mg Fe/g dry weight; high risk) [15]. This example is consistent with the experience of clinicians who may receive widely varying estimates of the hepatic iron concentration in the same patient evaluated contemporaneously by different MRI scanners.…”

Noninvasive MRI-Based Liver Iron Quantification: Methodic Approaches, Practical Applicability and Significance

“…Subsequent revalidation of the method on the basis of 223 patients [23] showed a certain range of the results with an average deviation compared to liver biopsy of 35 %. In contrast to the nonlinear relationship between R 2 and liver iron content in a range of up to 40 mg/g dry weight stated in the studies by St. Pierre et al [20,23], Wood showed a linear course (as is theoretically to be expected), but only for a maximum liver iron concentration of up to 30 mg/g dry weight ( fig. 2 in ref.…”