Eisenquantifizierung mittels MRT bei Eisenüberladung

Zusammenfassung

Eisen ist als essenzielles Spurenelement in viele Stoffwechselaktivitäten involviert. Wie wichtig eine optimale Eisenversorgung ist zeigt, dass nach WHO Angaben ca. 30 % der Weltbevölkerung an einer eisenmangelbedingten Anämie leidet. Dagegen ist die hereditäre Hämochromatose die häufigste monogen vererbte Erkrankung (Prävalenz homozygoter Merkmalsträger in Deutschland 1:200 – 300). Während die Diagnostik und Therapie einer Eisenmangelanämie einem relativ einfachen Prozedere unterliegen, stellen die Diagnose und insbesondere die Quantifizierung der Organeisenüberladung eine ungleich schwerere Herausforderung dar. Dies ist von großer klinischer Bedeutung, da die Gesamtkonzentration des Körper- bzw. Organeisens der ausschlaggebende Parameter für die Prognose bei Eisenüberladungen ist. So wurde 2001 auf dem Internationalen Workshop des NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) dokumentiert, dass ein klarer klinischer Nutzen für die nicht invasive, quantitative, sichere und akkurate Bestimmung des Körpereisengehalts zur Verbesserung der Diagnose und Therapie bei Eisenüberladungskrankheiten besteht.

Abstract

Iron as an essential nutrient is involved in multiple metabolic activities. The importance of a sufficient iron supply is stressed by the fact that, according to WHO data, about 30 % of the global population suffers from iron deficiency and resulting anemia. In contrast, hereditary hemochromatosis is the most common monogeneous inherited disease (prevalence of homozygous genotype 1:200 – 300 in Germany). While iron-induced anemia can be handled by relatively simple diagnostic and therapeutic management, the diagnosis and quantification of organ iron overload is far more challenging. This is of great clinical impact, as the overall body and organ iron concentration is the crucial prognostic parameter in iron overload disease. In 2001 the international workshop of NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) concluded that a quantitative, noninvasive, safe, and accurate approach for the assessment of body iron storage is needed to improve the diagnosis and management of patients with iron overload.

Key words

MR-functional imaging - iron overload - iron quantification - relaxometry

• Literatur

• 1 Brittenham GM, Badman DG. Noninvasive measurement of iron: report of an NIDDK workshop. Blood 2003; 101: 15-19
• 2 Papanikolaou G, Tzilianos M, Christakis JI et al. Hepcidin in iron overload disorders. Blood 2005; 105: 4103-4105
• 3 Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann N Y Acad Sci 1998; 850: 191-201
• 4 Siddique A, Kowdley KV. Review article: the iron overload syndromes. Aliment Pharmacol Ther 2012; 35: 876-893
• 5 Feder JN, Gnirke A, Thomas W et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996; 13: 399-408
• 6 Pietrangelo A. Hereditary hemochromatosis – a new look at an old disease. N Engl J Med 2004; 350: 2383-2397
• 7 Strohmeyer G, Niederau C, Stremmel W. Survival and causes of death in hemochromatosis. Observations in 163 patients. Ann N Y Acad Sci 1988; 526: 245-257
• 8 Pietrangelo A. Hereditary hemochromatosis. Biochim Biophys Acta 2006; 1763: 700-710
• 9 Cario H, Stahnke K, Sander S et al. Epidemiological situation and treatment of patients with thalassemia major in Germany: results of the German multicenter beta-thalassemia study. Ann Hematol 2000; 79: 7-12
• 10 Seldrum S, Pierard S, Moniotte S et al. Iron overload in polytransfused patients without heart failure is associated with subclinical alterations of systolic left ventricular function using cardiovascular magnetic resonance tagging. J Cardiovasc Magn Reson 2011; 13: 23
• 11 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. Pediatr Blood Cancer 2007; 49: 329-332
• 12 Harmatz P, Butensky E, Quirolo K et al. Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy. Blood 2000; 96: 76-79
• 13 Nielsen P, Engelhardt R, Dullmann J et al. Non-invasive liver iron quantification by SQUID-biosusceptometry and serum ferritin iron as new diagnostic parameters in hereditary hemochromatosis. Blood Cells Mol Dis 2002; 29: 451-458
• 14 Butensky E, Fischer R, Hudes M et al. Variability in hepatic iron concentration in percutaneous needle biopsy specimens from patients with transfusional hemosiderosis. Am J Clin Pathol 2005; 123: 146-152
• 15 de Bucourt M, Busse R, Zada O et al. CT-guided biopsies: quality, complications and impact on treatment: a retrospective initial quality control. Fortschr Röntgenstr 2011; 183: 842-848
• 16 Marinelli M, Cuneo S, Gianesin B et al. Non-invasive measurement of iron overload in the human body. IEEE 2006; 16: 1513-1518
• 17 Fischer R, Harmatz P, Nielsen P. Does liver biopsy overestimate liver iron concentration?. Blood 2006; 108: 1775-1776 ; author reply 1776
• 18 Taylor BA, Loeffler RB, Song R et al. Simultaneous field and R2 mapping to quantify liver iron content using autoregressive moving average modeling. J Magn Reson Imaging 2012; 35: 1125-1132
• 19 Wang ZJ, Fischer R, Chu Z et al. Assessment of cardiac iron by MRI susceptometry and R2* in patients with thalassemia. Magn Reson Imaging 2010; 28: 363-371
• 20 Stark DD, Bass NM, Moss AA et al. Nuclear magnetic resonance imaging of experimentally induced liver disease. Radiology 1983; 148: 743-751
• 21 Wood JC, Ghugre N. Magnetic resonance imaging assessment of excess iron in thalassemia, sickle cell disease and other iron overload diseases. Hemoglobin 2008; 32: 85-96
• 22 Ghugre NR, Coates TD, Nelson MD et al. Mechanisms of tissue-iron relaxivity: nuclear magnetic resonance studies of human liver biopsy specimens. Magn Reson Med 2005; 54: 1185-1193
• 23 Anderson LJ, Holden S, Davis B et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 2001; 22: 2171-2179
• 24 Engelhardt R, Langkowski JH, Fischer R et al. Liver iron quantification: studies in aqueous iron solutions, iron overloaded rats, and patients with hereditary hemochromatosis. Magn Reson Imaging 1994; 12: 999-1007
• 25 Wood JC, Otto-Duessel M, Aguilar M et al. Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy. Circulation 2005; 112: 535-543
• 26 Chavhan GB, Babyn PS, Thomas B et al. Principles, techniques, and applications of T2*-based MR imaging and its special applications. Radiographics 2009; 29: 1433-1449
• 27 Stark DD, Moseley ME, Bacon BR et al. Magnetic resonance imaging and spectroscopy of hepatic iron overload. Radiology 1985; 154: 137-142
• 28 Jensen JH, Tang H, Tosti CL et al. Separate MRI quantification of dispersed (ferritin-like) and aggregated (hemosiderin-like) storage iron. Magn Reson Med 2010; 63: 1201-1209
• 29 Gandon Y, Guyader D, Heautot JF et al. Hemochromatosis: diagnosis and quantification of liver iron with gradient-echo MR imaging. Radiology 1994; 193: 533-538
• 30 Sheth S, Tang H, Jensen JH et al. Methods for noninvasive measurement of tissue iron in Cooley's anemia. Ann N Y Acad Sci 2005; 1054: 358-372
• 31 Alustiza JM, Artetxe J, Castiella A et al. MR quantification of hepatic iron concentration. Radiology 2004; 230: 479-484
• 32 Kaltwasser JP, Gottschalk R, Schalk KP et al. Non-invasive quantitation of liver iron-overload by magnetic resonance imaging. Br J Haematol 1990; 74: 360-363
• 33 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
• 34 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
• 35 Angelucci E, Brittenham GM, McLaren CE et al. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med 2000; 343: 327-331
• 36 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. Haematologica 2008; 93: 741-752
• 37 Gandon Y, Olivie D, Guyader D et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004; 363: 357-362
• 38 Fischer MA, Reiner CS, Raptis D et al. Quantification of liver iron content with CT-added value of dual-energy. Eur Radiol 2011; 21: 1727-1732
• 39 Korkusuz H, Abbas Raschidi B, Keese D et al. Diagnosing and Quantification of Acute Alcohol Intoxication – Comparison of Dual-Energy CT with Biochemical Analysis: Initial Experience. Fortschr Röntgenstr 2012; 184: 1126-1130
• 40 Yamamura J, Grosse R, Graessner J et al. Distribution of cardiac iron measured by magnetic resonance imaging (MRI)-R2*. J Magn Reson Imaging 2010; 32: 1104-1109
• 41 Patton N, Brown G, Leung M et al. Observational study of iron overload as assessed by magnetic resonance imaging in an adult population of transfusion-dependent patients with beta thalassaemia: significant association between low cardiac T2* < 10 ms and cardiac events. Intern Med J 2010; 40: 419-426
• 42 Borgna-Pignatti C, Rugolotto S, De Stefano P et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004; 89: 1187-1193
• 43 Tanner MA, Galanello R, Dessi C et al. Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction. J Cardiovasc Magn Reson 2008; 10: 12
• 44 Kim D, Jensen JH, Wu EX et al. Rapid monitoring of iron-chelating therapy in thalassemia major by a new cardiovascular MR measure: the reduced transverse relaxation rate. NMR Biomed 2011; 24: 771-777
• 45 Carpenter JP, He T, Kirk P et al. On T2* magnetic resonance and cardiac iron. Circulation 2011; 123: 1519-1528
• 46 Papakonstantinou O, Alexopoulou E, Economopoulos N et al. Assessment of iron distribution between liver, spleen, pancreas, bone marrow, and myocardium by means of R2 relaxometry with MRI in patients with beta-thalassemia major. J Magn Reson Imaging 2009; 29: 853-859
• 47 Roth C, Pekrun A, Bartz M et al. Short stature and failure of pubertal development in thalassaemia major: evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin secretion. Eur J Pediatr 1997; 156: 777-783
• 48 Christoforidis A, Haritandi A, Perifanis V et al. MRI for the determination of pituitary iron overload in children and young adults with beta-thalassaemia major. Eur J Radiol 2007; 62: 138-142
• 49 Argyropoulou MI, Metafratzi Z, Kiortsis DN et al. T2 relaxation rate as an index of pituitary iron overload in patients with beta-thalassemia major. Am J Roentgenol 2000; 175: 1567-1569
• 50 Au WY, Lam WW, Chu W et al. A T2* magnetic resonance imaging study of pancreatic iron overload in thalassemia major. Haematologica 2008; 93: 116-119
• 51 Papakonstantinou O, Ladis V, Kostaridou S et al. The pancreas in beta-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbances. Eur Radiol 2007; 17: 1535-1543
• 52 Noetzli LJ, Papudesi J, Coates TD et al. Pancreatic iron loading predicts cardiac iron loading in thalassemia major. Blood 2009; 114: 4021-4026
• 53 Yamamura J, Grosse R, Jarisch A et al. Pancreatic exocrine function and cardiac iron in patients with iron overload and with thalassemia. Pediatr Blood Cancer 2011; 57: 674-676
• 54 Noetzli LJ, Mittelman SD, Watanabe RM et al. Pancreatic iron and glucose dysregulation in thalassemia major. Am J Hematol 2012; 87: 155-160
• 55 De Sanctis V, De Sanctis E, Ricchieri P et al. Mild subclinical hypothyroidism in thalassaemia major: prevalence, multigated radionuclide test, clinical and laboratory long-term follow-up study. Pediatr Endocrinol Rev 2008; 6: 174-180
• 56 Schein A, Enriquez C, Coates TD et al. Magnetic resonance detection of kidney iron deposition in sickle cell disease: a marker of chronic hemolysis. J Magn Reson Imaging 2008; 28: 698-704
• 57 Mathys C, Blondin D, Wittsack HJ et al. T2’ Imaging of Native Kidneys and Renal Allografts – a Feasibility Study. Fortschr Röntgenstr 2011; 183: 112-119
• 58 Papakonstantinou O, Foufa K, Benekos O et al. Use of fat suppression in R(2) relaxometry with MRI for the quantification of tissue iron overload in beta-thalassemic patients. Magn Reson Imaging 2012; 30: 926-933
• 59 Soliman AT, Nasr I, Thabet A et al. Human chorionic gonadotropin therapy in adolescent boys with constitutional delayed puberty vs. those with beta-thalassemia major. Metabolism 2005; 54: 15-23