Quantification of liver iron with MRI: State of the art and remaining challenges

Hernando, Diego; Levin, Yakir S.; Sirlin, Claude B.; Reeder, Scott B.

doi:10.1002/jmri.24584

Cited by 237 publications

(276 citation statements)

References 138 publications

(243 reference statements)

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“…Nanoliposomal carriers may thus exhibit comparably faster drug release rates than therapeutic nanoparticles with a more erosive, slower release mechanism (27,43), which could possibly explain the lack of correlation between lesion response to nal-IRI and late binding events of FMX in this study. R2 and R2 Ã mapping are accepted clinical tools for evaluating tissue iron concentrations, both for iron overload disorders (44,45) and for tracking of ultrasmall superparamagnetic iron oxide particles (18,24,46). To enable accurate lesion FMX assessments, baseline MRI signals were subtracted from later time points, and FMX phantom reference was used with all scans.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study

Ramanathan

Korn

Raghunand

et al. 2017

Clinical Cancer Research

157

153

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Purpose: To determine whether deposition characteristics of ferumoxytol (FMX) iron nanoparticles in tumors, identified by quantitative MRI, may predict tumor lesion response to nanoliposomal irinotecan (nal-IRI).Experimental Design: Eligible patients with previously treated solid tumors had FMX-MRI scans before and following (1, 24, and 72 hours) FMX injection. After MRI acquisition, R2 Ã signal was used to calculate FMX levels in plasma, reference tissue, and tumor lesions by comparison with a phantom-based standard curve. Patients then received nal-IRI (70 mg/m 2 free base strength) biweekly until progression. Two percutaneous core biopsies were collected from selected tumor lesions 72 hours after FMX or nal-IRI.Results: Iron particle levels were quantified by FMX-MRI in plasma, reference tissues, and tumor lesions in 13 of 15 eligible patients. On the basis of a mechanistic pharmacokinetic model, tissue permeability to FMX correlated with early FMX-MRI signals at 1 and 24 hours, while FMX tissue binding contributed at 72 hours. Higher FMX levels (ranked relative to median value of multiple evaluable lesions from 9 patients) were significantly associated with reduction in lesion size by RECIST v1.1 at early time points (P < 0.001 at 1 hour and P < 0.003 at 24 hours FMX-MRI, one-way ANOVA). No association was observed with post-FMX levels at 72 hours. Irinotecan drug levels in lesions correlated with patient's time on treatment (Spearman r ¼ 0.7824; P ¼ 0.0016).Conclusions: Correlation between FMX levels in tumor lesions and nal-IRI activity suggests that lesion permeability to FMX and subsequent tumor uptake may be a useful noninvasive and predictive biomarker for nal-IRI response in patients with solid tumors.

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Section: Discussionmentioning

confidence: 99%

Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study

Ramanathan

Korn

Raghunand

et al. 2017

Clinical Cancer Research

157

153

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“…Although the best curve fitting and number of echoes strategy have yet to be defined and the number of echoes might be smaller for PDFF quantification without decreasing accuracy [37], our 12-echo approach improves R2* quantification. Of importance, the first echo and the echo spacing should be as short as possible to better capture the signal decay in cases of severe iron overload [38]. 3 T MR magnets have higher signal-to-noise ratio and overall quality than 1.5 T units, being advantageous for abdominal imaging.…”

Section: Discussionmentioning

confidence: 99%

Accurate simultaneous quantification of liver steatosis and iron overload in diffuse liver diseases with MRI

et al. 2017

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Purpose: To evaluate the diagnostic performances of 3 Tesla multi-echo chemical shift-encoded gradient echo magnetic resonance (MECSE-MR) imaging to simultaneously quantify liver steatosis and iron overload in a wide spectrum of diffuse liver diseases having biopsy as reference standard. Methods: MECSE-MR-acquired images were used to calculate fat fraction and iron content in a single breathhold in 109 adult patients. Proton density fat fraction (PDFF) was prospectively estimated using complexbased data reconstruction with multipeak fat modeling. Water R2* was used to estimate iron content. Biopsy was obtained in all cases, grading liver steatosis, siderosis, inflammation, and fibrosis. Differences in PDFF and R2* values across histopathological grades were analyzed, and ROC curves analyses evaluated the MR diagnostic performance. Results: Calculated fat fraction measurements showed significant differences (p < 0.001) among steatosis grades, being unaffected by the presence of inflammation or fibrosis (p ‡ 0.05). A strong correlation was found between fat fraction and steatosis grade (R S = 0.718, p < 0.001). Iron deposits did not affect fat fraction quantitation (p ‡ 0.05), except in cases with severe iron overload (grade 4). A strong positive correlation was also observed between R2* measurements and iron grades (R S = 0.704, p < 0.001). Calculated R2* values were not different across grades of steatosis, inflammation, and fibrosis (p ‡ 0.05). Conclusion: A MECSE-MR sequence simultaneously quantifies liver steatosis and siderosis, regardless coexisting liver inflammation or fibrosis, with high accuracy in a wide spectrum of diffuse liver disorders. This sequence can be acquired within a single breath-hold and can be implemented in the routine MR evaluation of the liver.

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“…The requirement for manual interaction in some of the current analysis methods adds a subjective factor which, although often clinically insignificant in myocardial T2* measurements 27, may present challenges in liver T2* determination 9, 19, 28. Iron overload is usually first found in the liver 29.…”

Section: Discussionmentioning

confidence: 99%

Validation of a new t2* algorithm and its uncertainty value for cardiac and liver iron load determination from MRI magnitude images

Bidhult

Xanthis

Liljekvist

et al. 2015

Magnetic Resonance in Med

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PurposeTo validate an automatic algorithm for offline T2* measurements, providing robust, vendor‐independent T2*, and uncertainty estimates for iron load quantification in the heart and liver using clinically available imaging sequences.MethodsA T2* region of interest (ROI)‐based algorithm was developed for robustness in an offline setting. Phantom imaging was performed on a 1.5 Tesla system, with clinically available multiecho gradient‐recalled‐echo (GRE) sequences for cardiac and liver imaging. A T2* single‐echo GRE sequence was used as reference. Simulations were performed to assess accuracy and precision from 2000 measurements. Inter‐ and intraobserver variability was obtained in a patient study (n = 23).ResultsSimulations: Accuracy, in terms of the mean differences between the proposed method and true T2* ranged from 0–0.73 ms. Precision, in terms of confidence intervals of repeated measurements, was 0.06–4.74 ms showing agreement between the proposed uncertainty estimate and simulations. Phantom study: Bias and variability were 0.26 ± 4.23 ms (cardiac sequence) and −0.23 ± 1.69 ms (liver sequence). Patient study: Intraobserver variability was similar for experienced and inexperienced observers (0.03 ± 1.44 ms versus 0.16 ± 2.33 ms). Interobserver variability was 1.0 ± 3.77 ms for the heart and −0.52 ± 2.75 ms for the liver.ConclusionThe proposed algorithm was shown to provide robust T2* measurements and uncertainty estimates over the range of clinically relevant T2* values. Magn Reson Med, 2015. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Magn Reson Med 75:1717–1729, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance.

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Quantification of liver iron with MRI: State of the art and remaining challenges

Cited by 237 publications

References 138 publications

Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study

Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study

Accurate simultaneous quantification of liver steatosis and iron overload in diffuse liver diseases with MRI

Validation of a new t2* algorithm and its uncertainty value for cardiac and liver iron load determination from MRI magnitude images

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