PEDIATRIC RADIOLOGY / REVIEW PAPER
Iron overload in paediatric oncology: the role of radiology in diagnosing and monitoring secondary haemochromatosis
1
2nd Department of Radiology, Medical University of Gdansk, Poland
2
Department of Neurophysiology, Neuropsychology, and Neuroinformatics, Medical University of Gdansk, Poland
3
1st Department of Radiology, Medical University of Gdansk, Poland
Submission date: 2025-06-16
Final revision date: 2025-08-11
Acceptance date: 2025-08-12
Publication date: 2025-11-13
Corresponding author
Pol J Radiol, 2025; 90: 543-550
KEYWORDS
MRIpaediatric oncologyhepatic iron overloadsecondary haemochromatosispancreatic iron overloadspleen iron overload
TOPICS
ABSTRACT
Secondary haemochromatosis among paediatric oncologic patients is associated with various long-term complications. The liver is the most important organ for assessment of iron overload because the iron concentration is linearly correlated with total body iron stores.
In the paediatric population, liver biopsy is considered too invasive for routine use. Therefore, evaluation of iron overload with magnetic resonance imaging is an alternative method.
Reliable assessment of iron burden is necessary for early detection and severity grading. In the last 2 decades multiple methods for iron quantification with magnetic resonance imaging (MRI) have been developed. Both gradient-echo and spin-echo imaging, including signal intensity ratio and relaxometry strategies, are in clinical use. However, there are no universally accepted MRI protocols for paediatric oncology patients suspected of secondary haemochromatosis. If diagnosed and treated early, haemochromatosis progression can be distinctively altered.
Iron overload impacts hepatocytes, pancreas’s beta cells, heart, and spleen. Each organ displays distinct patterns of iron distribution, which require targeted imaging methods. This review will address the importance of using magnetic resonance imaging for iron measurements, as well as the evaluation for the liver, pancreas, and spleen.
REFERENCES (51)
1.
Sait S, Zaghloul N, Patel A, Shah T, Iacobas I, Calderwood S. Transfusion related iron overload in pediatric oncology patients treated at a tertiary care centre and treatment with chelation therapy. Pediatr Blood Cancer 2014; 61: 2319-2320.
2.
Das S, Misra A, Kashyap A, Meena S, Singh A, Aggarwal KC. Study of transfusion-related iron overload (trio) in pediatric patients with hematological malignancy and bone marrow failure syndromes. Am J Blood Res 2021; 11: 384-390.
3.
Gandon Y, Olivié D, Guyader D, Aubé C, Oberti F, Sebille V, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004; 363: 357-362.
4.
İdilman İS, Akata D, Özmen MN, Karçaaltıncaba M. Different forms of iron accumulation in the liver on MRI. Diagn Interv Radiol 2016; 22: 22. DOI: 10.5152/dir.2015.15094.
5.
Rose C, Vandevenne P, Bourgeois E, Cambier N, Ernst O. Liver iron content assessment by routine and simple magnetic resonance imaging procedure in highly transfused patients. Eur J Haematol 2006; 77: 145-149.
6.
Paisant A, Boulic A, Bardou-Jacquet E, Bannier E, d’Assignies G, Lainé F, et al. Assessment of liver iron overload by 3 T MRI. Abdom Radiol (NY) 2017; 42: 1713. DOI: 10.1007/S00261-017-1077-8.
7.
Alexopoulou E, Stripeli F, Baras P, Seimenis I, Kattamis A, Ladis V, et al. R2 relaxometry with MRI for the quantification of tissue iron overload in beta-thalassemic patients. J Magn Reson Imaging 2006; 23: 163-170.
8.
Henninger B, Zoller H, Rauch S, Finkenstedt A, Schocke M, Jaschke W, et al. R2* relaxometry for the quantification of hepatic iron overload: biopsy-based calibration and comparison with the literature. Rofo 2015; 187: 472-479.
9.
Hankins JS, McCarville MB, Loeffler RB, Smeltzer MP, Onciu M, Hoffer FA, et al. R2* magnetic resonance imaging of the liver in patients with iron overload. Blood 2009; 113: 4853-4855.
10.
Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD, 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.
11.
Garbowski MW, Carpenter JP, Smith G, Roughton M, Alam MH, He T, et al. Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron concentration and comparison with R2 Ferriscan. J Cardiovasc Magn Reson 2014; 16. DOI: 10.1186/1532-429X-16-40.
12.
Hernando D, Cook RJ, Qazi N, Longhurst CA, Diamond CA, Reeder SB. Complex confounder-corrected R2* mapping for liver iron quantification with MRI. Eur Radiol 2021; 31: 264-275.
13.
d’Assignies G, Paisant A, Bardou-Jacquet E, Boulic A, Bannier E, Lainé F, et al. Non-invasive measurement of liver iron concentration using 3-Tesla magnetic resonance imaging: validation against biopsy. Eur Radiol 2018; 28: 2022-2030.
14.
Storey P, Thompson AA, Carqueville CL, Wood JC, De Freitas RA, Rigsby CK. R2* imaging of transfusional iron burden at 3T and comparison with 1.5T. J Magn Reson Imaging 2007; 25: 540-547.
15.
Hernando D, Kramer JH, Reeder SB. Multipeak fat-corrected complex R2* relaxometry: theory, optimization, and clinical validation. Magn Reson Med 2013; 70: 1319-1331.
16.
Aslan E, Luo JW, Lesage A, Paquin P, Cerny M, Chin ASL, et al. MRI-based R2* mapping in patients with suspected or known iron overload. Abdom Radiol (NY) 2021; 46: 2505-2515.
17.
Henninger B, Plaikner M, Zoller H, Viveiros A, Kannengiesser S, Jaschke W, et al. Performance of different Dixon-based methods for MR liver iron assessment in comparison to a biopsy-validated R2* relaxometry method. Eur Radiol 2021; 31: 2252-2262.
18.
Colgan TJ, Zhao R, Roberts NT, Hernando D, Reeder SB. Limits of fat quantification in the presence of iron overload. J Magn Reson Imaging 2021; 54: 1166-1174.
19.
Argyropoulou MI, Astrakas L. MRI evaluation of tissue iron burden in patients with beta-thalassaemia major. Pediatr Radiol 2007; 37: 1191-1200.
20.
Argyropoulou MI, Kiortsis DN, Astrakas L, Metafratzi Z, Chalissos N, Efremidis SC. Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: a T2 relaxometry study. Eur Radiol 2007; 17: 3025-3030.
21.
Holmqvist AS, Olsen JH, Andersen KK, Licht SDF, Hjorth L, Garwicz S, et al. Adult life after childhood cancer in Scandinavia: diabetes mellitus following treatment for cancer in childhood. Eur J Cancer 2014; 50: 1169-1175.
22.
Trovillion EM, Schubert L, Dietz AC. Iron overload in survivors of childhood cancer. J Pediatr Hematol Oncol 2018; 40: 396-400.
23.
Sawicka-Zukowska M, Kretowska-Grunwald A, Kania A, Topczewska M, Niewinski H, Bany M, et al. Iron overload in children with acute lymphoblastic and acute myeloblastic leukemia – experience of one center. Cancers (Basel) 2024; 16. DOI: 10.3390/cancers16020367.
24.
Queiroz-Andrade M, Blasbalg R, Ortega CD, Rodstein MAM, Baroni RH, Rocha MS, et al. MR imaging findings of iron overload. Radiographics 2009; 29: 1575-1589.
25.
Papakonstantinou OG, Maris TG, Kostaridou V, Gouliamos AD, Koutoulas GK, Kalovidouris AE, et al. Assessment of liver iron overload by T2-quantitative magnetic resonance imaging: correlation of T2-QMRI measurements with serum ferritin concentration and histologic grading of siderosis. Magn Reson Imaging 1995; 13: 967-977.
26.
Ernst O, Sergent G, Bonvarlet P, Canva-Delcambre V, Paris JC, L’Herminé C. Hepatic iron overload: Diagnosis and quantification with MR imaging. Am J Roentgenol 1997; 168: 1205-1218.
27.
St. Pierre TG, Clark PR, Chua-Anusorn W, Fleming AJ, Jeffrey GP, Olynyk JK, et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005; 105: 855-861.
28.
Hoe HG, Git KA, Loh CK, Abdul Latiff Z, Hong J, Abdul Hamid H, et al. Magnetic resonance imaging T2* of the pancreas value using an online software tool and correlate with T2* value of myocardium and liver among patients with transfusion-dependent thalassemia major. Front Radiol 2022; 2: 943102. DOI: 10.3389/FRADI.2022.943102.
29.
Meloni A, Pistoia L, Putti MC, Longo F, Corigliano E, Ricchi P, et al. Pancreatic iron in pediatric transfusion-dependent beta-thalassemia patients: A longitudinal MRI study. Pediatr Blood Cancer 2024; 71: e30923. DOI: 10.1002/PBC.30923.
30.
Papakonstantinou O, Ladis V, Kostaridou S, Maris T, Berdousi H, Kattamis C, 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.
31.
Pfeifer CD, Schoennagel BP, Grosse R, Wang ZJ, Graessner J, Niel-sen P, et al. Pancreatic iron and fat assessment by MRI-R2* in patients with iron overload diseases. J Magn Res Imaging 2015; 42: 196-203.
32.
Giamanco N, Warwick AB, Crouch G. Identifying iron overload in pediatric oncology patients. Blood 2014; 124: 2682. DOI: 10.1182/BLOOD.V124.21.2682.2682.
33.
Matter RM, Allam KE, Sadony AM. Gradient-echo magnetic resonance imaging study of pancreatic iron overload in young Egyptian beta-thalassemia major patients and effect of splenectomy. Diabetol Metab Syndr 2010; 2: 23. DOI: DOI: 10.1186/1758-5996-2-23.
34.
Au WY, Lam WWM, Chu W, Tam S, Wong WK, Liang R, et al. A T2* magnetic resonance imaging study of pancreatic iron overload in thalassemia major. Haematologica 2008; 93: 116-119.
35.
Midiri M, Lo Casto A, Sparacia G, D’Angelo P, Malizia R, Finazzo M, et al. MR imaging of pancreatic changes in patients with transfusion-dependent beta-thalassemia major. AJR Am J Roentgenol 1999; 173: 187-192.
36.
Rostoker G, Laroudie M, Blanc R, Griuncelli M, Loridon C, Lepeytre F, et al. Histological scores validate the accuracy of hepatic iron load measured by signal intensity ratio and R2* relaxometry MRI in dialysis patients. J Clin Med 2020; 9: 17. DOI: 10.3390/JCM9010017.
37.
Papakonstantinou O, Drakonaki EE, Maris T, Vasiliadou A, Papadakis A, Gourtsoyiannis N. MR imaging of spleen in beta-thalassemia major. Abdom Imaging 2015; 40: 2777-2782.
38.
Emy PY, Levin TL, Sheth SS, Ruzal-Shapiro C, Garvin J, Berdon WE. Iron overload in reticuloendothelial systems of pediatric oncology patients who have undergone transfusions: MR observations. AJR Am J Roentgenol 1997; 168: 1011-1015.
39.
Çetinçakmak MG, Hattapoglu S, Söker M, Ekici F, Yilmaz K, Göya C, et al. Evaluation of the relationship between splenic iron overload and liver, heart and muscle features evident on T2*-weighted magnetic resonance imaging. Adv Clin Exp Med 2020; 29: 475-480.
40.
Miya T, Kondo H, Gemma A. Serum iron levels increased by cancer chemotherapy correlate the chemotherapy-induced nausea and vomiting. Int J Clin Oncol 2018; 23: 1196-1200.
41.
Wang Y, Juan L, Ma X, Wang D, Ma H, Chang Y, et al. Specific hemosiderin deposition in spleen induced by a low dose of cisplatin: altered iron metabolism and its implication as an acute hemosiderin formation model. Curr Drug Metab 2010; 11: 507. DOI: 10.2174/138920010791636149.
42.
Hershko C, Link G, Konijn AM, Cabantchik ZI. Objectives and mechanism of iron chelation therapy. Ann N Y Acad Sci 2005; 1054: 124-135.
43.
Wood JC. Magnetic resonance imaging measurement of iron overload. Curr Opin Hematol 2007; 14: 183-190.
44.
Wood JC. Use of Magnetic resonance imaging to monitor iron overload. Hematol Oncol Clin North Am 2014; 28: 747. DOI: 10.1016/J.HOC.2014.04.002.
45.
Lutz K, Von Komorowski G, Dürken M, Engelhardt R, Dinter DJ. Myocardial iron overload in transfusion-dependent pediatric patients with acute leukemia. Pediatr Blood Cancer 2008; 51: 691-693.
46.
Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 2001; 22: 2171-2179.
47.
Gandon Y, Guyader D, Heautot JF, Reda MI, Yaouanq J, Buhé T, et al. Hemochromatosis: diagnosis and quantification of liver iron with gradient-echo MR imaging. Radiology 1994; 193: 533-538.
48.
Chapchap EC, Marques M, Silva A, Alves De Assis R, Kerbauy LN, Da M, et al. Cardiac iron overload evaluation in thalassaemic patients using T2* magnetic resonance imaging following chelation therapy: a multicentre cross-sectional study. Hematol Transfus Cell Ther 2023; 45: 7-15.
49.
Reeder SB, Yokoo T, França M, Hernando D, Alberich-Bayarri Á, Alústiza JM, et al. Quantification of liver iron overload with MRI: review and guidelines from the ESGAR and SAR. Radiology 2023; 307. DOI: 10.1148/radiol.221856.
50.
Maris TG, Papakonstantinou O, Chatzimanoli V, Papadakis A, Pagonidis K, Papanikolaou N, et al. Myocardial and liver iron status using a fast T*2 quantitative MRI (T*2qMRI) technique. Magn Reson Med 2007; 57: 742-753.
51.
Schwenzer NF, MacHann J, Haap MM, Martirosian P, Schraml C, Liebig G, et al. T2* relaxometry in liver, pancreas, and spleen in a healthy cohort of one hundred twenty-nine subjects-correlation with age, gender, and serum ferritin. Invest Radiol 2008; 43: 854-860.
Share
RELATED ARTICLE
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
