Methods and Applications for Quantitative Measurement of Iron in Human_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Dan ,  SONG Bin , YUAN Fang , TANG Hehan.

Department of Radiology， West China Hospital of Sichuan University， Chengdu 610041， Sichuan Province， China;

Corresponding author：

SONG Bin, Email: cjr.songbin@vip.163.com

Keywords：

Liver iron content; CT; Superconducting quantum interference device investigation; MRI; Suscepti-bility weighted imaging

Video：

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Objective 　To summarize the methods and applications for quantitative measurement of iron in human.
Methods 　The methods and applications for quantitative measurement of iron in human were analyzed retrospectively via reviewing the literatures domesticly and abroad， and summarized the advantages and disadvantages respectively.
Results 　The methods for quantitative measurement of iron included laboratory tests， pathology examinations， CT， superconducting quantum interference device investigation （SQUID）， and MRI.
Conclusions 　Laboratory test is the most simple and economic method for quantitative measurement of iron in human. Percutaneous liver biopsy is the gold standard
method. Radiologic examinations， especially MRI， may be main methods of measuring liver iron content in future.

Citation： LIU Dan,SONG Bin,YUAN Fang,TANG Hehan.. Methods and Applications for Quantitative Measurement of Iron in Human. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(12): 1347-1351. doi: Copy

1.	Borgna-Pignatti C， Castriota-Scanderbeg A. Methods for evaluatingiron stores and efficacy of chelation in transfusional hemosiderosis[J]. Haematologica， 1991， 76(5)：409-413.
2.	Batts KP. Iron overload syndromes and the liver[J]. Mod Pathol， 2007， 20(1)： 31-39.
3.	Hentze MW， Muckenthaler MU， Andrews NC. Balancing acts：molecular control of mammalian iron metabolism[J]. Cell， 2004， 117(3)： 285-297.
4.	Rund D， Rachmilewitz E. Beta-thalassemia[J]. N Engl J Med， 2005， 353(11)： 1135-1146.
5.	Guyader D， Gandon Y. Quantification of iron overload[J]. Bull Acad Natl Med， 2000， 184(2)：337-347.
6.	Pakbaz Z， Fischer R， Fung E， et al. Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients[J]. Pediatr Blood Cancer， 2007， 49(3)：329-332.
7.	Angelucci E， Barosi G， Camaschella C， et al. Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders[J]. Haematologica， 2008， 93(5)： 741-752.
8.	Imbert-Bismut F， Charlotte F， Turlin B， et al. Low hepatic iron concentration：evaluation of two complementary methods，colorimetric assay and iron histological scoring[J]. J Clin Pathol， 1999， 52(6)： 430-434.
9.	Angelucci E， Brittenham GM， McLaren CE， et al. Hepatic iron concentration and total body iron stores in thalassemia major[J]. N Engl J Med， 2000， 343(5)：327-331.
10.	Barry M. Liver iron concentration， stainable iron， and total body storage iron[J]. Gut， 1974， 15(5)： 411-415.
11.	Valberg LS， Simon JB， Manley PN， et al. Distribution of storage iron as body stores expand in patients with hemochromatosis[J]. J Lab Clin Med， 1975， 86(3)：479-489.
12.	Bassett ML， Halliday JW， Powell LW. Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis[J]. Hepatology， 1986， 6(1)：24-29.
13.	Deugnier YM， Turlin B， Powell LW， et al. Differentiationbetween heterozygotes and homozygotes in genetic hemochromatosis by means of a histological hepatic iron index：a study of 192 cases[J]. Hepatology， 1993， 17(1)：30-34.
14.	Scheuer PJ， Williams R， Muir AR. Hepatic pathology in relativesof patients with hemochromatosis[J]. J Pathol Bacteriol， 1962， 84：53-64.
15.	Ludwig J， Batts KP， Moyer TP， et al. Liver biopsy diagnosis of homozygous hemochromatosis： a diagnostic algorithm[J]. Mayo Clin Proc， 1993， 68(3)：263-267.
16.	Deugnier YM， Loréal O， Turlin B， et al. Liver pathology in genetic hemochromatosis：a review of 135 homozygous cases and their bioclinical correlations[J]. Gastroenterology， 1992， 102(6)：2050-2059.
17.	Ludwig J， Hashimoto E， Porayko MK， et al. Hemosiderosis in cirrhosis：a study of 447 native livers[J]. Gastroenterology， 1997， 112(3)：882-888.
18.	Guyader D， Gandon Y， Deugnier Y， et al. Evaluation of computedtomography in the assessment of liver iron overload：a study of 46 cases of idiopathic hemochromatosis[J]. Gastroenterology， 1989， 97(3)： 737-743.
19.	Howard JM， Ghent CN， Carey LS， et al. Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload[J]. Gastroenterology， 1983， 84(2)：209-215.
20.	Houang MT， Arozena X， Skalicka A， et al. Correlation between computed tomographic values and liver iron content in thalassaemia major with iron overload[J]. Lancet， 1979， 1(8130)： 1322-1323.
21.	Goldberg HI， Cann CE， Moss AA， et al. Noninvasive quantitation of liver iron in dogs with hemochromatosis using dual-energy CT scanning[J]. Invest Radiol， 1982， 17(4)：375-380.
22.	Fischer MA， Reiner CS， Raptis D， et al. Quantification of liver iron content with CT-added value of dual-energy[J]. Eur Radiol，2011， 21(8)： 1727-1732.
23.	Goldman IS， Winkler ML， Raper SE， et al. Increased hepatic density and phospholipidosis due to amiodarone[J]. AJR Am J Roentgenol， 1985， 144(3)：541-546.
24.	De Maria M， De Simone G， Laconi A， et al. Gold storage in the liver：appearance on CT scans[J]. Radiology， 1986， 159(2)：355-356.
25.	Gomori JM， Horev G， Tamary H， et al. Hepatic iron overload：quantitative MR imaging[J]. Radiology， 1991， 179(2)：367-369.
26.	Farrell DE， Tripp JH， Zanzucchi PE， et al. Magnetic measurement of human iron stores[J]. IEEE Trans Magnetics， 1980， 16(5)： 818-823.
27.	Brittenham GM， Farrell DE， Harris JW， et al. Magnetic-susceptibility measurement of human iron stores[J]. N Engl J Med， 1982， 307(27)： 1671-1675.
28.	Sheth S. SQUID biosusceptometry in the measurement of hepatic iron[J]. Pediatr Radiol， 2003， 33(6)： 373-377.
29.	Nielsen P， Engelhardt R， Düllmann J， et al. Non-invasive liver iron quantification by SQUID-biosusceptometry and serum ferritiniron as new diagnostic parameters in hereditary hemochromatosis[J]. Blood Cells Mol Dis， 2002， 29(3)： 451-458.
30.	Fischer R， Tiemann CD， Engelhardt R， et al. Assessment of iron stores in children with transfusion siderosis by biomagnetic liver susceptometry[J]. Am J Hematol， 1999， 60(4)：289-299.
31.	Fischer R， Piga A， Harmatz P， et al. Monitoring long-termefficacy of iron chelation treatment with biomagnetic liver susceptometry[J]. Ann N Y Acad Sci， 2005， 1054： 350-357.
32.	Idbaih A， Boukobza M， Crassard I， et al. MRI of clot in cerebralvenous thrombosis：high diagnostic value of susceptibility-weighted images[J]. Stroke， 2006， 37(4)：991-995.
33.	Nielsen P， Engelhardt R， Duerken M， et al. Using SQUID biomagnetic liver susceptometry in the treatment of thalassemia and other iron loading diseases[J]. Transfus Sci， 2000， 23(3)：257-258.
34.	Gandon Y， Olivié D， Guyader D， et al. Non-invasive assessment of hepatic iron stores by MRI[J]. Lancet， 2004， 363(9406)：357-362.
35.	Jensen PD. Evaluation of iron overload[J]. Br J Haematol， 2004， 124(6)：697-711.
36.	Jensen PD， Jensen FT， Christensen T， et al. Non-invasiveassessment of tissue iron overload in the liver by magnetic resonanceimaging[J]. Br J Haematol， 1994， 87(1)： 171-184.
37.	Bonkovsky HL， Rubin RB， Cable EE， et al. Hepatic ironconcentration：noninvasive estimation by means of MR imaging techniques[J]. Radiology， 1999， 212(1)： 227-234.
38.	Papakonstantinou OG， Maris TG， Kostaridou V， et al. Assessment of liver iron overload by T2-quantitative magnetic resonance imaging：correlation of T2-QMRI measurements with serumferritin concentration and histologic grading of siderosis[J]. Magn Reson Imaging， 1995， 13(7)： 967-977.
39.	Anderson LJ， Holden S， Davis B， et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload[J]. Eur Heart J， 2001， 22(23)： 2171-2179.
40.	Ernst O， Sergent G， Bonvarlet P， et al. Hepatic iron overload：diognosis and quantification with MR imaging[J]. AJR Am J Roentgenol， 1997， 168(5)：1205-1208.
41.	Queiroz-Andrade M， Blasbalg R， Ortega CD， et al. MR Imagingfindings of iron overload[J]. Radiographics， 2009， 29(6)：1575-1589.
42.	Tziomalos K， Perifanis V. Liver iron content determination by magnetic resonance imaging[J]. World J Gastroenterol， 2010， 16(13)： 1587-1597.
43.	Westwood M， Anderson LJ， Firmin DN， et al. A single breath-hold multiecho T2* cardiovascular magnetic resonance technique for diagnosis of myocardial iron overload[J]. J Magn Reson Imaging， 2003， 18(1)：33-39.
44.	Hankins JS， McCarville MB， Loeffler RB，et al. R2* magnetic resonance imaging of the liver in patients with iron overload[J]. Blood， 2009， 113(20)：4853-4855.
45.	Wood JC， Enriquez C， Ghugre N， et al. MRI R2 and R2* mappingaccurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients[J]. Blood， 2005， 106(4)：1460-1465.
46.	St Pierre TG， Clark PR， Chua-Anusorn W. Single spin-echo protontransverse relaxometry of iron loaded-liver[J]. NMR Biomed，2004， 17(7)： 446-458.
47.	Argyropoulou MI， Astrakas L. MRI evaluation of tissue iron burdenin patients with beta-thalassaemia major[J]. Pediatr Radiol， 2007， 37(12)： 1191-1200.
48.	Haacke EM， Reichenbach JR. Susceptibility weighted imaging in MRI：basic concepts and clinical applications[M]. Hoboken， New Jersey：John Wiley&Sons， 2011：10.
49.	Angelucci E， Giovagnoni A， Valeri G， et al. Limitations of magnetic resonance imaging in measurement of hepatic iron[J]. Blood， 1997， 90(12)： 4736-4742.
50.	Reichenbach JR， Venkatesan R， Schillinger DJ， et al. Small vesselsin the human brain：MR venography with deoxyhemoglobin as an intrinsic contrast agent[J]. Radiology， 1997， 204(1)：272-277.
51.	Haacke EM， Xu Y， Cheng YC， et al. Susceptibility weighted imaging (SWI)[J]. Magn Reson Med， 2004， 52(3)： 612-618.
52.	Dai Y， Zeng M， Li R， et al. Improving detection of siderotic nodules in cirrhotic liver with a multi-breath-hold susceptibility weighted imaging technique[J]. J Magn Reson Imaging， 2011， 34(2)： 318-325.
53.	Tao R， Zhang J， Dai Y， et al. An in vitro and in vivo analysisof the correlation between susceptibility-weighted imaging phase values and R2* in cirrhotic livers[J]. PLoS One， 2012， 7(9)： e45477.
54.	Haacke EM， Miao Y， Liu M， et al. Correlation of putative iron content as represented by changes in R2* and phase with age in deep gray matter of healthy adults[J]. J Magn Reson Imaging， 2010， 32(3)： 561-576.

1. Borgna-Pignatti C， Castriota-Scanderbeg A. Methods for evaluatingiron stores and efficacy of chelation in transfusional hemosiderosis[J]. Haematologica， 1991， 76(5)：409-413.
2. Batts KP. Iron overload syndromes and the liver[J]. Mod Pathol， 2007， 20(1)： 31-39.
3. Hentze MW， Muckenthaler MU， Andrews NC. Balancing acts：molecular control of mammalian iron metabolism[J]. Cell， 2004， 117(3)： 285-297.
4. Rund D， Rachmilewitz E. Beta-thalassemia[J]. N Engl J Med， 2005， 353(11)： 1135-1146.
5. Guyader D， Gandon Y. Quantification of iron overload[J]. Bull Acad Natl Med， 2000， 184(2)：337-347.
6. Pakbaz Z， Fischer R， Fung E， et al. Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients[J]. Pediatr Blood Cancer， 2007， 49(3)：329-332.
7. Angelucci E， Barosi G， Camaschella C， et al. Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders[J]. Haematologica， 2008， 93(5)： 741-752.
8. Imbert-Bismut F， Charlotte F， Turlin B， et al. Low hepatic iron concentration：evaluation of two complementary methods，colorimetric assay and iron histological scoring[J]. J Clin Pathol， 1999， 52(6)： 430-434.
9. Angelucci E， Brittenham GM， McLaren CE， et al. Hepatic iron concentration and total body iron stores in thalassemia major[J]. N Engl J Med， 2000， 343(5)：327-331.
10. Barry M. Liver iron concentration， stainable iron， and total body storage iron[J]. Gut， 1974， 15(5)： 411-415.
11. Valberg LS， Simon JB， Manley PN， et al. Distribution of storage iron as body stores expand in patients with hemochromatosis[J]. J Lab Clin Med， 1975， 86(3)：479-489.
12. Bassett ML， Halliday JW， Powell LW. Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis[J]. Hepatology， 1986， 6(1)：24-29.
13. Deugnier YM， Turlin B， Powell LW， et al. Differentiationbetween heterozygotes and homozygotes in genetic hemochromatosis by means of a histological hepatic iron index：a study of 192 cases[J]. Hepatology， 1993， 17(1)：30-34.
14. Scheuer PJ， Williams R， Muir AR. Hepatic pathology in relativesof patients with hemochromatosis[J]. J Pathol Bacteriol， 1962， 84：53-64.
15. Ludwig J， Batts KP， Moyer TP， et al. Liver biopsy diagnosis of homozygous hemochromatosis： a diagnostic algorithm[J]. Mayo Clin Proc， 1993， 68(3)：263-267.
16. Deugnier YM， Loréal O， Turlin B， et al. Liver pathology in genetic hemochromatosis：a review of 135 homozygous cases and their bioclinical correlations[J]. Gastroenterology， 1992， 102(6)：2050-2059.
17. Ludwig J， Hashimoto E， Porayko MK， et al. Hemosiderosis in cirrhosis：a study of 447 native livers[J]. Gastroenterology， 1997， 112(3)：882-888.
18. Guyader D， Gandon Y， Deugnier Y， et al. Evaluation of computedtomography in the assessment of liver iron overload：a study of 46 cases of idiopathic hemochromatosis[J]. Gastroenterology， 1989， 97(3)： 737-743.
19. Howard JM， Ghent CN， Carey LS， et al. Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload[J]. Gastroenterology， 1983， 84(2)：209-215.
20. Houang MT， Arozena X， Skalicka A， et al. Correlation between computed tomographic values and liver iron content in thalassaemia major with iron overload[J]. Lancet， 1979， 1(8130)： 1322-1323.
21. Goldberg HI， Cann CE， Moss AA， et al. Noninvasive quantitation of liver iron in dogs with hemochromatosis using dual-energy CT scanning[J]. Invest Radiol， 1982， 17(4)：375-380.
22. Fischer MA， Reiner CS， Raptis D， et al. Quantification of liver iron content with CT-added value of dual-energy[J]. Eur Radiol，2011， 21(8)： 1727-1732.
23. Goldman IS， Winkler ML， Raper SE， et al. Increased hepatic density and phospholipidosis due to amiodarone[J]. AJR Am J Roentgenol， 1985， 144(3)：541-546.
24. De Maria M， De Simone G， Laconi A， et al. Gold storage in the liver：appearance on CT scans[J]. Radiology， 1986， 159(2)：355-356.
25. Gomori JM， Horev G， Tamary H， et al. Hepatic iron overload：quantitative MR imaging[J]. Radiology， 1991， 179(2)：367-369.
26. Farrell DE， Tripp JH， Zanzucchi PE， et al. Magnetic measurement of human iron stores[J]. IEEE Trans Magnetics， 1980， 16(5)： 818-823.
27. Brittenham GM， Farrell DE， Harris JW， et al. Magnetic-susceptibility measurement of human iron stores[J]. N Engl J Med， 1982， 307(27)： 1671-1675.
28. Sheth S. SQUID biosusceptometry in the measurement of hepatic iron[J]. Pediatr Radiol， 2003， 33(6)： 373-377.
29. Nielsen P， Engelhardt R， Düllmann J， et al. Non-invasive liver iron quantification by SQUID-biosusceptometry and serum ferritiniron as new diagnostic parameters in hereditary hemochromatosis[J]. Blood Cells Mol Dis， 2002， 29(3)： 451-458.
30. Fischer R， Tiemann CD， Engelhardt R， et al. Assessment of iron stores in children with transfusion siderosis by biomagnetic liver susceptometry[J]. Am J Hematol， 1999， 60(4)：289-299.
31. Fischer R， Piga A， Harmatz P， et al. Monitoring long-termefficacy of iron chelation treatment with biomagnetic liver susceptometry[J]. Ann N Y Acad Sci， 2005， 1054： 350-357.
32. Idbaih A， Boukobza M， Crassard I， et al. MRI of clot in cerebralvenous thrombosis：high diagnostic value of susceptibility-weighted images[J]. Stroke， 2006， 37(4)：991-995.
33. Nielsen P， Engelhardt R， Duerken M， et al. Using SQUID biomagnetic liver susceptometry in the treatment of thalassemia and other iron loading diseases[J]. Transfus Sci， 2000， 23(3)：257-258.
34. Gandon Y， Olivié D， Guyader D， et al. Non-invasive assessment of hepatic iron stores by MRI[J]. Lancet， 2004， 363(9406)：357-362.
35. Jensen PD. Evaluation of iron overload[J]. Br J Haematol， 2004， 124(6)：697-711.
36. Jensen PD， Jensen FT， Christensen T， et al. Non-invasiveassessment of tissue iron overload in the liver by magnetic resonanceimaging[J]. Br J Haematol， 1994， 87(1)： 171-184.
37. Bonkovsky HL， Rubin RB， Cable EE， et al. Hepatic ironconcentration：noninvasive estimation by means of MR imaging techniques[J]. Radiology， 1999， 212(1)： 227-234.
38. Papakonstantinou OG， Maris TG， Kostaridou V， et al. Assessment of liver iron overload by T2-quantitative magnetic resonance imaging：correlation of T2-QMRI measurements with serumferritin concentration and histologic grading of siderosis[J]. Magn Reson Imaging， 1995， 13(7)： 967-977.
39. Anderson LJ， Holden S， Davis B， et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload[J]. Eur Heart J， 2001， 22(23)： 2171-2179.
40. Ernst O， Sergent G， Bonvarlet P， et al. Hepatic iron overload：diognosis and quantification with MR imaging[J]. AJR Am J Roentgenol， 1997， 168(5)：1205-1208.
41. Queiroz-Andrade M， Blasbalg R， Ortega CD， et al. MR Imagingfindings of iron overload[J]. Radiographics， 2009， 29(6)：1575-1589.
42. Tziomalos K， Perifanis V. Liver iron content determination by magnetic resonance imaging[J]. World J Gastroenterol， 2010， 16(13)： 1587-1597.
43. Westwood M， Anderson LJ， Firmin DN， et al. A single breath-hold multiecho T2* cardiovascular magnetic resonance technique for diagnosis of myocardial iron overload[J]. J Magn Reson Imaging， 2003， 18(1)：33-39.
44. Hankins JS， McCarville MB， Loeffler RB，et al. R2* magnetic resonance imaging of the liver in patients with iron overload[J]. Blood， 2009， 113(20)：4853-4855.
45. Wood JC， Enriquez C， Ghugre N， et al. MRI R2 and R2* mappingaccurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients[J]. Blood， 2005， 106(4)：1460-1465.
46. St Pierre TG， Clark PR， Chua-Anusorn W. Single spin-echo protontransverse relaxometry of iron loaded-liver[J]. NMR Biomed，2004， 17(7)： 446-458.
47. Argyropoulou MI， Astrakas L. MRI evaluation of tissue iron burdenin patients with beta-thalassaemia major[J]. Pediatr Radiol， 2007， 37(12)： 1191-1200.
48. Haacke EM， Reichenbach JR. Susceptibility weighted imaging in MRI：basic concepts and clinical applications[M]. Hoboken， New Jersey：John Wiley&Sons， 2011：10.
49. Angelucci E， Giovagnoni A， Valeri G， et al. Limitations of magnetic resonance imaging in measurement of hepatic iron[J]. Blood， 1997， 90(12)： 4736-4742.
50. Reichenbach JR， Venkatesan R， Schillinger DJ， et al. Small vesselsin the human brain：MR venography with deoxyhemoglobin as an intrinsic contrast agent[J]. Radiology， 1997， 204(1)：272-277.
51. Haacke EM， Xu Y， Cheng YC， et al. Susceptibility weighted imaging (SWI)[J]. Magn Reson Med， 2004， 52(3)： 612-618.
52. Dai Y， Zeng M， Li R， et al. Improving detection of siderotic nodules in cirrhotic liver with a multi-breath-hold susceptibility weighted imaging technique[J]. J Magn Reson Imaging， 2011， 34(2)： 318-325.
53. Tao R， Zhang J， Dai Y， et al. An in vitro and in vivo analysisof the correlation between susceptibility-weighted imaging phase values and R2* in cirrhotic livers[J]. PLoS One， 2012， 7(9)： e45477.
54. Haacke EM， Miao Y， Liu M， et al. Correlation of putative iron content as represented by changes in R2* and phase with age in deep gray matter of healthy adults[J]. J Magn Reson Imaging， 2010， 32(3)： 561-576.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Methods and Applications for Quantitative Measurement of Iron in Human

Abstract Full text Figures/Tables Video References Cited by

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