Impact of MRI technique on clinical decision-making in patients with liver iron overload: comparison of FerriScan- versus R2*-derived liver iron concentration

Abstract

Objectives

The purpose of this study was to compare clinical decision-making in iron overload patients using FerriScan and an R2*-based approach.

Methods

One-hundred and six patients were imaged at two consecutive timepoints (454 ± 158 days) on a 1.5-T Siemens MAGNETOM Avanto Fit scanner. For both timepoints, patients underwent the standard FerriScan MRI protocol. During the second exam, each patient additionally underwent R2*-MRI mapping. For each patient, a retrospective (simulated) decision was made to increase, decrease, or maintain chelator levels. Two different decision models were considered: The fixed threshold model assumed that chelator adjustments are based strictly on fixed liver iron concentration (LIC) thresholds. Decisions made with this model depend only on the most recent LIC value and do not require any clinician input. The second model utilized decisions made by two hematologists retrospectively based on trends between two consecutive LIC values. Agreement (κA) between hematologists (i.e., interobserver variability) was compared with the agreement (κB) between a single hematologist using the two different LIC techniques.

Results

Good agreement between R2*- and FerriScan-derived decisions was achieved for the fixed threshold model. True positive/negative rates were greater than 80%, and false positive/negative rates were less than 10%. ROC analysis yielded areas under the curve greater than 0.95. In the second model, the agreement in clinical decision-making for the two scenarios (κA vs. κB) was equal at the 95% confidence level.

Conclusions

Switching to R2*-based LIC estimation from FerriScan has the same level of agreement in patient management decisions as does switching from one hematologist to another.

Key Points

• Good agreement between R2*- and FerriScan-derived decisions in liver iron overload patient management

• Switching to R2*-based LIC estimation from FerriScan has the same level of agreement in patient management decisions as does switching from one hematologist to another.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Abbreviations

κ :

Kappa value

AUC:

Area under the curve

LIC:

Liver iron concentration

LIC(R2∗):

R2*-derived estimate of FerriScan LIC

LIC FerriScan :

FerriScan-derived estimate of LIC

MRI:

Magnetic resonance imaging

ROC:

Receiver operating characteristic

References

  1. 1.

    Olivieri NF, Brittenham GM (1997) Iron-chelating therapy and the treatment of thalassemia. Blood 89:739–761

    CAS  Article  Google Scholar 

  2. 2.

    Ferriscan (2015) MRI measurement of liver iron concentration. Available via http://www.resonancehealth.com/images/files/FerriScan/FerriScan%20Fact%20Sheet%20Mar%202015.pdf

  3. 3.

    St Pierre TG, Clark PR, Chua-Anusorn W et al (2005) Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 105:855–861

    CAS  Article  Google Scholar 

  4. 4.

    Mark Belletrutti LB, Corriveau-Bourque C, Ezzat H et al (2018) Consensus statement of clinical care of patients with thalassemia in Canada. Available via https://www.canhaem.org/wp-content/uploads/2018/10/consensus-statment-Thalassemia-Final.pdf

  5. 5.

    Chan WC, Tejani Z, Budhani F, Massey C, Haider MA (2014) R2* as a surrogate measure of FerriScan iron quantification in thalassemia. J Magn Reson Imaging 39:1007–1011

    Article  Google Scholar 

  6. 6.

    Garbowski MW, Carpenter JP, Smith G et al (2014) Biopsy-based calibration of T2*magnetic resonance for estimation of liver iron concentration and comparison with R2 FerriScan. J Cardiovasc Magn Reson 16:40

  7. 7.

    Runge JH, Akkerman EM, Troelstra MA, Nederveen AJ, Beuers U, Stoker J (2016) Comparison of clinical MRI liver iron content measurements using signal intensity ratios, R (2) and R (2)*. Abdom Radiol (NY) 41:2123–2131

  8. 8.

    Wood JC, Enriquez C, Ghugre N et al (2005) MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 106:1460–1465

    CAS  Article  Google Scholar 

  9. 9.

    Hankins JS, McCarville MB, Loeffler RB et al (2009) R2* magnetic resonance imaging of the liver in patients with iron overload. Blood 113:4853–4855

    CAS  Article  Google Scholar 

  10. 10.

    Henninger B, Zoller H, Rauch S et al (2015) R2* relaxometry for the quantification of hepatic iron overload: biopsy-based calibration and comparison with the literature. Rofo 187:472–479

  11. 11.

    Jhaveri KS, Kannengiesser SAR, Ward R, Kuo K, Sussman MS (2019) Prospective evaluation of an R2*method for assessing liver iron concentration (LIC) against FerriScan: derivation of the calibration curve and characterization of the nature and source of uncertainty in the relationship. J Magn Reson Imaging 49:1467–1474

    Article  Google Scholar 

  12. 12.

    Zhong XD, Nickel MD, Kannengiesser SAR, Dale BM, Kiefer B, Bashir MR (2014) Liver fat quantification using a multi-step adaptive fitting approach with multi-echo GRE imaging. Magn Reson Med 72:1353–1365

    Article  Google Scholar 

  13. 13.

    Sheth S (2018) Monitoring of iron overload in transfusion-dependent thalassemia (TDT). New York. Available via http://www.thalassemia.org/boduw/wp-content/uploads/2018/05/Monitoring-of-Iron-Overload-in-Transfusion-Dependent-Thalassemia-TDT-1.pdf

  14. 14.

    Efron B, Tibshirani RJ (1993) An introduction to the bootstrap. Chapman & Hall, New York

    Google Scholar 

  15. 15.

    Tanhehco YC, Shi PA (2019) Chapter 52 - Transfusion management of patients with sickle cell disease and thalassemia. In: Shaz BH, Hillyer CD, Reyes Gil M (eds) Transfusion medicine and hemostasis (third edition). Elsevier, pp 325–335

  16. 16.

    Papakonstantinou O, Ladis V, Kostaridou S et al (2007) The pancreas in beta-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbances. Eur Radiol 17:1535–1543

    Article  Google Scholar 

  17. 17.

    Lekawanvijit S, Chattipakorn N (2009) Iron overload thalassemic cardiomyopathy: Iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol 25:213–218

    CAS  Article  Google Scholar 

  18. 18.

    Borgna-Pignatti C, Rugolotto S, De Stefano P et al (2004) Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 89:1187–1193

    PubMed  Google Scholar 

  19. 19.

    Nichols-Vinueza DX, White MT, Powell AJ, Banka P, Neufeld EJ (2014) MRI guided iron assessment and oral chelator use improve iron status in thalassemia major patients. Am J Hematol 89:684–688

    CAS  Article  Google Scholar 

Download references

Funding

The authors state that this work has not received any funding.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Kartik S. Jhaveri.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Kartik Jhaveri.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

All MRI data used in this manuscript were acquired as part of a previous study (Jhaveri et al, JMRI 2018, pp. 1467–1474). The purpose of this previous study was twofold: first, to define a calibration curve that related R2*-derived liver iron concentration (LIC) values to FerriScan-derived LIC values; second, to characterize the nature of the uncertainty in the relationship between those two quantities. In the present manuscript, (simulated) clinical decisions were made using the R2*- and FerriScan-derived LIC values respectively. An analysis was performed to determine the agreement in clinical decision-making between these two approaches. Although the same data is used for both studies, there is no overlap in the nature or scope of the work.

Methodology

• diagnostic or prognostic study

• performed at one institution

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sussman, M.S., Ward, R., Kuo, K.H.M. et al. Impact of MRI technique on clinical decision-making in patients with liver iron overload: comparison of FerriScan- versus R2*-derived liver iron concentration. Eur Radiol 30, 1959–1968 (2020). https://doi.org/10.1007/s00330-019-06450-y

Download citation

Keywords

  • Magnetic resonance imaging (MRI)
  • Iron
  • Liver
  • Decision-making
  • Uncertainty