Download PDF
Rofo 2016; 188(11): 1031-1036
DOI: 10.1055/s-0042-115570
Review
© Georg Thieme Verlag KG Stuttgart · New York

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

Nicht invasive MRT-basierte Bestimmung des Leber-Eisen-Gehalts: Methodische Ansätze, Anwendbarkeit in der Praxis und Aussagekraft
A. P. Wunderlich
1   Section for Experimental Radiology, Universitätsklinikum Ulm, Germany
4   Clinic for Diagnostic and Interventional Radiology, Universitätsklinikum Ulm, Germany
,
H. Cario
2   Department of Pediatrics and Adolescent Medicine, Universitätsklinik Ulm, Germany
,
M. S. Juchems
3   Diagnostic and Interventional Radiology, Konstanz Hospital, Konstanz, Germany
,
M. Beer
4   Clinic for Diagnostic and Interventional Radiology, Universitätsklinikum Ulm, Germany
,
S. A. Schmidt
4   Clinic for Diagnostic and Interventional Radiology, Universitätsklinikum Ulm, Germany
› Author Affiliations
Further Information

Publication History

27 October 2015

29 July 2016

Publication Date:
14 September 2016 (online)

Also available at
   Permissions and Reprints

Abstract

Due to the dependence of transverse relaxation times T2 and T2* on tissue iron content, MRI offers different options for the determination of iron concentration. These are the time-consuming spin-echo sequence as well as the gradient-echo sequence. For the latter, several data analysis approaches have been proposed, with different requirements for acquisition and post-processing: the mathematically challenging R2* analysis and the signal-intensity ratio method with its high demand on the signal homogeneity of MR images. Furthermore, special procedures currently under evaluation are presented as future prospects: quantitative susceptibility imaging, as a third approach for analyzing gradient echo data, and multi-contrast spin-echo using repeated refocusing pulses. MR theory, as far as needed for understanding the methods, is briefly depicted.

Key points:

• Description of underlying technology of different MRI-based procedures for liver iron quantification

• Applicability of these methods in clinical practice

• Validity of the methods, i. e. positive and negative predictive value, if available

Citation Format:

• Wunderlich AP, Cario H, Juchems MS et al. Noninvasive MRI-Based Liver Iron Quantification: Methodic Approaches, Practical Applicability and Significance. Fortschr Röntgenstr 2016; 188: 1031 – 1036

Zusammenfassung

Aufgrund des Einflusses des Gewebe-Eisengehalts auf die transversalen Relaxationszeiten T2 und T2* bietet die MRT verschiedene Möglichkeiten zur In-vivo-Bestimmung der Eisenkonzentration. Dies sind im Einzelnen die zeitaufwändige Spin-Echo- sowie die Gradienten-Echo-Methode. Bei Letzterer gibt es prinzipiell mehrere Ansätze zur Datenauswertung, mit unterschiedlichen Voraussetzungen für Aufnahmetechnik und Nachverarbeitung: Einerseits die mathematisch anspruchsvolle R2*-Analyse, andererseits das Signalintensitätsverfahren, das hohe Anforderungen an die Signalhomogenität der MRT-Bilder stellt. Darauf aufbauende bzw. weiterführende Methoden sind: Die quantitative Suszeptibilitäts-Bestimmung als dritter Ansatz zur Auswertung von Gradienten-Echo-Daten, sowie die Multi-Kontrast Spin-Echo-Technik mit wiederholten Refokussierungspulsen. Die Theorie der MRT, sofern für das Verständnis der Methoden notwendig, wird in aller Kürze beleuchtet.

Key words

abdomen - MR-imaging - iron

Deutscher Artikel/German Article

 

  • References

  • 1 Wood JC. History and current impact of cardiac magnetic resonance imaging on the management of iron overload. Circulation 2009; 120: 1937-1939
    CrossrefPubMedGoogle Scholar
  • 2 Borgna-Pignatti C, Cappellini MD, De Stefano P et al. Survival and complications in thalassemia. Annals of the New York Academy of Sciences 2005; 1054: 40-47
    CrossrefPubMedGoogle Scholar
  • 3 Borgna-Pignatti C, Garani MC, Forni GL et al. Hepatocellular carcinoma in thalassaemia: an update of the Italian Registry. British journal of haematology 2014; 167: 121-126
    CrossrefPubMedGoogle Scholar
  • 4 Hernando D, Levin YS, Sirlin CB et al. Quantification of liver iron with MRI: state of the art and remaining challenges. JMRI 2014; 40: 1003-1021
    CrossrefPubMedGoogle Scholar
  • 5 Wood JC. Estimating tissue iron burden: current status and future prospects. British journal of haematology 2015; 170: 15-28
    CrossrefPubMedGoogle Scholar
  • 6 Steinbicker AU, Muckenthaler MU. Out of balance – systemic iron homeostasis in iron-related disorders. Nutrients 2013; 5: 3034-3061
    CrossrefPubMedGoogle Scholar
  • 7 Cario H, Grosse R, Janssen G et al. Guidelines for diagnosis and treatment of secondary iron overload in patients with congenital anemia. Klinische Padiatrie 2010; 222: 399-406
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Puliyel M, Sposto R, Berdoukas VA et al. Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload. American journal of hematology 2014; 89: 391-394
    CrossrefPubMedGoogle Scholar
  • 9 Taher AT, Musallam KM, Wood JC et al. Magnetic resonance evaluation of hepatic and myocardial iron deposition in transfusion-independent thalassemia intermedia compared to regularly transfused thalassemia major patients. American journal of hematology 2010; 85: 288-290
    CrossrefPubMedGoogle Scholar
  • 10 Ghugre NR, Coates TD, Nelson MD et al. Mechanisms of tissue-iron relaxivity: nuclear magnetic resonance studies of human liver biopsy specimens. MRM 2005; 54: 1185-1193
    CrossrefPubMedGoogle Scholar
  • 11 Emond MJ, Bronner MP, Carlson TH et al. Quantitative study of the variability of hepatic iron concentrations. Clinical chemistry 1999; 45: 340-346
    PubMedGoogle Scholar
  • 12 Stark DD, Moseley ME, Bacon BR et al. Magnetic resonance imaging and spectroscopy of hepatic iron overload. Radiology 1985; 154: 137-142
    CrossrefPubMedGoogle Scholar
  • 13 Brasch RC, Wesbey GE, Gooding CA et al. Magnetic resonance imaging of transfusional hemosiderosis complicating thalassemia major. Radiology 1984; 150: 767-771
    CrossrefPubMedGoogle Scholar
  • 14 Hernandez RJ, Sarnaik SA, Lande I et al. MR evaluation of liver iron overload. JCAT 1988; 12: 91-94
    PubMedGoogle Scholar
  • 15 Rocchi E, Cassanelli M, Borghi A et al. Magnetic resonance imaging and different levels of iron overload in chronic liver disease. Hepatology 1993; 17: 997-1002
    CrossrefPubMedGoogle Scholar
  • 16 Anderson LJ, Holden S, Davis B et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. European heart journal 2001; 22: 2171-2179
    CrossrefPubMedGoogle Scholar
  • 17 Wood JC, Enriquez C, Ghugre N et al. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 2005; 106: 1460-1465
    CrossrefPubMedGoogle Scholar
  • 18 Alustiza JM, Artetxe J, Castiella A et al. MR quantification of hepatic iron concentration. Radiology 2004; 230: 479-484
    CrossrefPubMedGoogle Scholar
  • 19 Gandon Y, Olivie D, Guyader D et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004; 363: 357-362
    CrossrefPubMedGoogle Scholar
  • 20 St Pierre TG, Clark PR, Chua-anusorn W et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005; 105: 855-861
    CrossrefPubMedGoogle Scholar
  • 21 Yokoo T, Browning JD. Fat and iron quantification in the liver: past, present, and future. Topics in magnetic resonance imaging 2014; 23: 73-94
    CrossrefPubMedGoogle Scholar
  • 22 Sarigianni M, Liakos A, Vlachaki E et al. Accuracy of magnetic resonance imaging in diagnosis of liver iron overload: a systematic review and meta-analysis. Clinical gastroenterology and hepatology 2015; 13: 55-63 e55
    CrossrefPubMedGoogle Scholar
  • 23 St Pierre TG, El-Beshlawy A, Elalfy M et al. Multicenter validation of spin-density projection-assisted R2-MRI for the noninvasive measurement of liver iron concentration. MRM 2014; 71: 2215-2223
    CrossrefPubMedGoogle Scholar
  • 24 Chandarana H, Lim RP, Jensen JH et al. Hepatic iron deposition in patients with liver disease: preliminary experience with breath-hold multiecho T2*-weighted sequence. Am J Roentgenol 2009; 193: 1261-1267
    CrossrefPubMedGoogle Scholar
  • 25 Hope TA, Ohliger MA, Qayyum A. MR imaging of diffuse liver disease: from technique to diagnosis. Radiologic clinics of North America 2014; 52: 709-724
    CrossrefPubMedGoogle Scholar
  • 26 Ghugre NR, Enriquez CM, Coates TD et al. Improved R2* measurements in myocardial iron overload. JMRI 2006; 23: 9-16
    CrossrefPubMedGoogle Scholar
  • 27 Hernando D, Kramer JH, Reeder SB. Multipeak fat-corrected complex R2* relaxometry: theory, optimization, and clinical validation. MRM 2013; 70: 1319-1331
    CrossrefPubMedGoogle Scholar
  • 28 Sirlin CB, Reeder SB. Magnetic resonance imaging quantification of liver iron. Magnetic resonance imaging clinics of North America 2010; 18: 359-381, ix
    CrossrefPubMedGoogle Scholar
  • 29 Hamilton G, Yokoo T, Bydder M et al. In vivo characterization of the liver fat (1)H MR spectrum. NMR in biomedicine 2011; 24: 784-790
    CrossrefPubMedGoogle Scholar
  • 30 Hernando D, Kuhn JP, Mensel B et al. R2* estimation using "in-phase" echoes in the presence of fat: the effects of complex spectrum of fat. JMRI 2013; 37: 717-726
    CrossrefPubMedGoogle Scholar
  • 31 Christoforidis A, Perifanis V, Spanos G et al. MRI assessment of liver iron content in thalassamic patients with three different protocols: comparisons and correlations. European journal of haematology 2009; 82: 388-392
    CrossrefPubMedGoogle Scholar
  • 32 Garbowski MW, Carpenter JP, Smith G et al. Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron concentration and comparison with R2 Ferriscan. Journal of Cardiovascular Magnetic Resonance 2014; 16: 40
    CrossrefPubMedGoogle Scholar
  • 33 Hankins JS, McCarville MB, Loeffler RB et al. R2* magnetic resonance imaging of the liver in patients with iron overload. Blood 2009; 113: 4853-4855
    CrossrefPubMedGoogle Scholar
  • 34 McCarville MB, Hillenbrand CM, Loeffler RB et al. Comparison of whole liver and small region-of-interest measurements of MRI liver R2* in children with iron overload. Pediatric radiology 2010; 40: 1360-1367
    CrossrefPubMedGoogle Scholar
  • 35 Virtanen JM, Komu ME, Parkkola RK. Quantitative liver iron measurement by magnetic resonance imaging: in vitro and in vivo assessment of the liver to muscle signal intensity and the R2* methods. Magnetic resonance imaging 2008; 26: 1175-1182
    CrossrefPubMedGoogle Scholar
  • 36 Henninger B, Zoller H, Rauch S et al. R2* relaxometry for the quantification of hepatic iron overload: biopsy-based calibration and comparison with the literature. Fortschr Röntgenstr 2015; 187: 472-479
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Krafft AJ, Loeffler RB, Song R et al. Does fat suppression via chemically selective saturation affect R2*-MRI for transfusional iron overload assessment? A clinical evaluation at 1.5T and 3T. MRM 2015; DOI: 10.1002/mrm.25868.
    PubMedGoogle Scholar
  • 38 Henninger B, Kremser C, Rauch S et al. Evaluation of liver fat in the presence of iron with MRI using T2* correction: a clinical approach. European radiology 2013; 23: 1643-1649
    CrossrefPubMedGoogle Scholar
  • 39 Kuhn JP, Hernando D, Munoz del Rio A et al. Effect of multipeak spectral modeling of fat for liver iron and fat quantification: correlation of biopsy with MR imaging results. Radiology 2012; 265: 133-142
    CrossrefPubMedGoogle Scholar
  • 40 Ghugre NR, Doyle EK, Storey P et al. Relaxivity-iron calibration in hepatic iron overload: Predictions of a Monte Carlo model. MRM 2015; 74: 879-883
    CrossrefPubMedGoogle Scholar
  • 41 Juchems MS, Cario H, Schmid M et al. Liver iron content determined by MRI: spin-echo vs. gradient-echo. Fortschr Röntgenstr 2012; 184: 427-431
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Verlhac S, Morel M, Bernaudin F et al. Liver iron overload assessment by MRI R2* relaxometry in highly transfused pediatric patients: an agreement and reproducibility study. Diagnostic and interventional imaging 2015; 96: 259-264
    CrossrefPubMedGoogle Scholar
  • 43 Rose C, Vandevenne P, Bourgeois E et al. Liver iron content assessment by routine and simple magnetic resonance imaging procedure in highly transfused patients. European journal of haematology 2006; 77: 145-149
    CrossrefPubMedGoogle Scholar
  • 44 Wunderlich AP, Cario H, Bommer M et al. MRI-Based Liver Iron Content Determination at 3T in Regularly Transfused Patients by Signal Intensity Ratio Using an Alternative Analysis Approach Based on R2* Theory. Fortschr Rontgenstr 2016; 188: 846-852
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Wang ZJ, Fischer R, Chu Z et al. Assessment of cardiac iron by MRI susceptometry and R2* in patients with thalassemia. Magnetic resonance imaging 2010; 28: 363-371
    CrossrefPubMedGoogle Scholar
  • 46 Hernando D, Cook RJ, Diamond C et al. Magnetic susceptibility as a B0 field strength independent MRI biomarker of liver iron overload. MRM 2013; 70: 648-656
    CrossrefPubMedGoogle Scholar
  • 47 Jensen JH, Chandra R. Theory of nonexponential NMR signal decay in liver with iron overload or superparamagnetic iron oxide particles. MRM 2002; 47: 1131-1138
    CrossrefPubMedGoogle Scholar
  • 48 Jensen JH, Tang H, Tosti CL et al. Separate MRI quantification of dispersed (ferritin-like) and aggregated (hemosiderin-like) storage iron. MRM 2010; 63: 1201-1209
    CrossrefPubMedGoogle Scholar
  • 49 Tang H, Jensen JH, Sammet CL et al. MR characterization of hepatic storage iron in transfusional iron overload. JMRI 2014; 39: 307-316
    CrossrefPubMedGoogle Scholar
  • 50 Wood JC, Zhang P, Rienhoff H et al. Liver MRI is more precise than liver biopsy for assessing total body iron balance: a comparison of MRI relaxometry with simulated liver biopsy results. Magnetic resonance imaging 2015; 33: 761-767
    CrossrefPubMedGoogle Scholar