[en] Iron accumulation is observed in liver and spleen during hemochromatosis and important neurodegenerative diseases involve iron overload in brain. Storage of iron is ensured by ferritin, which contains a magnetic core. It causes a darkening on T2-weighted MR images. This work aims at improving the understanding of the NMR relaxation of iron loaded human tissues, which is necessary to develop protocols of iron content measurements by MRI.
Relaxation times measurements on brain, liver and spleen samples were realized at different magnetic fields. Iron content was determined by atomic emission spectroscopy. For all samples, the longitudinal relaxation rate (1/T1) of tissue protons decreases with the magnetic field up to 1 T, independently of iron content, while their transverse relaxation rate (1/T2) strongly increases with the field, either linearly, quadratically or a combination thereof. The extent of the inter-echo time dependence of 1/T2 also varies according to the sample. A combination of theoretical models is necessary to describe relaxation of iron containing tissues. This can be due to the presence, inside tissues, of ferritin clusters of different sizes and densities. When considering all samples, a correlation (r2=0.6) between 1/T1 and iron concentration is observed at 7.0 T. In contrast the correlation between 1/T2 and iron content is poor, even at high field (r2=0.14 at 7.0 T). Our results show that MRI methods based on T1 or T2 measurements will easily detect an iron overloading at high magnetic field, but won't provide an accurate quantification of tissue iron content at low iron concentrations.
Hocq, Aline ; Université de Mons > Faculté de Médecine et de Pharmacie > Physique biomédicale
Luhmer, Michel
Saussez, Sven ; Université de Mons > Faculté de Médecine et de Pharmacie > Service d'Anatomie humaine et Oncologie expérimentale
Louryan, S
Gillis, Pierre ; Université de Mons > Administration > Extension de l'Université ASBL ; Université de Mons > Faculté des Sciences > FS - Service du Doyen
Gossuin, Yves ; Université de Mons > Faculté de Médecine et de Pharmacie > Service de Physique biomédicale
Language :
English
Title :
Effect of magnetic field and iron content on NMR proton relaxation of liver, spleen and brain tissues
Publication date :
01 March 2015
Journal title :
Contrast Media and Molecular Imaging
ISSN :
1555-4309
Publisher :
John Wiley & Sons, Hoboken, United States - New Jersey
Volume :
10
Pages :
144-152
Peer reviewed :
Peer Reviewed verified by ORBi
Research unit :
M104 - Physique biomédicale
Research institute :
R550 - Institut des Sciences et Technologies de la Santé
Rasalkar DD, Chu WCW, Cheng FWT, Paunipagar BK, Shing MK, Li CK. Atypical location of germinoma in basal ganglia in adolescents: radiological features and treatment outcomes. Br J Radiol 2010; 83: 261-267.
Gossuin Y, Roch A, Muller RN, Gillis P, Lo Bue F. Anomalous nuclear magnetic relaxation of aqueous solutions of ferritin: an unprecedented first-order mechanism. Magn Reson Med 2002; 48: 959-964.
Brooks RA, Moiny F, Gillis P. On T2-shortening by weakly magnetized particles: the chemical exchange model. Magn Reson Med 2001; 45: 1014-1020.
Yablonskiy DY, Haacke EM. Theory of NMR signal behavior in magnetically inhomogeneous tissues: the static dephasing regime. Magn Reson Med 1994; 32: 749-763.
Gilles C, Bonville P, Wong KKW, Mann S. Non-Langevin behaviour of the uncompensated magnetization in nanoparticles of artificial ferritin. Eur Phys J B 2000; 17: 417-427.
Bartzokis G, Beckson M, Hance DB, Marx P, Foster JA, Marder SR. MR evaluation of age-related increase of brain iron in young adult and older normal males. Magn Reson Imag 1997; 15(1): 29-35.
Bartzokis G, Tishler TA. MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer's and Huntington's disease. Cell Mol Biol 2000; 46: 821-833.
Schenck JF. Imaging of brain iron by magnetic resonance: T2 relaxation at different field strengths. J Neurol Sci 1995; 134: 10-18.
Ziv K, Meir G, Harmelin A, Shimoni E, Klein E, Neeman M. Ferritin as a reporter gene for MRI: chronic liver over expression of h-ferritin during dietary iron supplementation and aging. NMR Biomed 2010; 23: 523-531.
Bulte JWM, Miller GF, Vymazal J, Brooks RA, Frank JA. Hepatic hemosiderosis in non-human primates: quantification of liver iron using different field strengths. Magn Reson Med 1997; 37: 530-536.
Vymazal J, Brooks RA, Baumgarner C, Tran V, Katz D, Bulte JWM, Bauminger ER, Di Chiro G. The relation between brain iron and NMR relaxation times: an in vitro study. Magn Reson Med 1996; 35: 56-61.
Bizzi A, Brooks RA, Brunetti A, Hill JM, Alger JR, Miletich RS, Francavilla TL, Di Chiro G. Role of iron and ferritin in MR imaging of the brain: a study in primates at different field strengths. Radiology 1990; 177: 59-65.
Oros-Peusquens AM, Laurila M, Shah NJ. Magnetic field dependence of the distribution of NMR relaxation times in the living human brain. Magn Reson Mater Phys 2008; 21: 131- 147.
Gossuin Y, Gillis P, Muller RN, Hocq A. Relaxation by clustered ferritin: a model for ferritin-induced relaxation in vivo. NMR Biomed 2007; 20: 749-756.
Mitsumori F, Watanabe H, Takaya N, Garwood M, Auerbach EJ, Michaeli S, Mangia S. Toward understanding transverse relaxation in human brain through its field dependence. Magn Reson Med 2012; 68: 947-953.
Hardy PA, Gash D, Yokel R, Andersen A, Ai Y, Zhang ZM. Correlation of R2 with total iron concentration in the brains of rhesus monkeys. J Magn Reson Imag 2005; 21: 118- 127.
House JH, St Pierre TG, Kowdley KV, Montine T, Connor J, Beard J, Berger J, Siddaiah N, Shankland E, Jin L-W. Correlation of proton transverse relaxation rates (R2) with iron concentrations in postmortem brain tissue from Alzheimer's disease patients. Magn Reson Med 2007; 57: 172-180.
House MJ, St Pierre TG, McLean C. 1.4T study of proton magnetic relaxation rates, iron concentrations, and plaque burden in Alzheimer's disease and control postmortem brain tissue. Magn Reson Med 2008; 60: 41-52.
Song R, Lin W, Chen Q, Asakura T, Wehrli FW, Song HK. Relationships between MR transverse relaxation parameters R2*, R2 and R2' and hepatic iron content in thalassemic mice at 1.5 T and 3 T. NMR Biomed 2008; 21: 574-580.
Vymazal J, Righini A, Brooks RA, Canesi M, Mariani C, Leonardi M, Pezzoli G. T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. Radiology 1999; 211: 489-495.
Gelman N, Gorell JM, Barker PB, Savage RM, Spickler EM, Windham JP, Knight RA. MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation rates and relation to estimated iron content. Radiology 1999; 210: 759-767.
Gelman N, Ewing JR, Gorell JM, Spickler EM, Solomon EG. Interregional variation of longitudinal relaxation rates in human brain at 3.0 T: relation to estimated iron and water contents. Magn Reson Med 2001; 45: 71-79.
Hikita T, Abe K, Sakoda S, Tanaka H, Murase K, Fujita N. Determination of transverse relaxation rate for estimating iron deposits in central nervous system. Neurosci Res 2005; 51: 67-71.
Mitsumori F, Watanabe H, Takaya N, Garwood M. Apparent transverse relaxation rate in human brain varies linearly with tissue iron concentration at 4.7 T. Magn Reson Med 2007; 58: 1054-1060.
Chen JC, Hardy PA, Clauberg M, Joshi JG, Parravano J, Deck JHN, Henkelman RM, Becker LE, Kucharczyk W. T2 values in the human brain: comparison with quantitative assays of iron and ferritin. Radiology 1989; 173: 521-526.
St Pierre TG, Clark PR, Chua-Anusorn W. Single spin-echo proton transverse relaxometry of iron-loaded liver. NMR Biomed 2004; 17: 446-458.
House MJ, St Pierre TG, Milward EA, Bruce DG, Olynyk JK. Relationship between brain R2 and liver and serum iron concentrations in elderly men. Magn Reson Med 2010; 63: 275-281.
Thomsen C, Wiggers P, Ring-Larsen H, Christiansen E, Dalhoj J, Henriksen O, Christoffersen P. Identification of patients with hereditary haemochromatosis by magnetic resonance imaging and spectroscopic relaxation-time measurements. Magn Reson Imag 1992; 10: 867-879.
Wood JC, Fassler JD, Meade T. Mimicking liver iron overload using liposomal ferritin preparations. Magn Reson Med 2004; 51: 607-611.
Wang ZJ, Haselgrove JC, Martin MB, Hubbard AM, Li S, Loomes K, Moore JR, Zhao H, Cohen AR. Evaluation of iron overload by single voxel MRS measurement of liver T2. J Magn Reson Imag 2002; 15: 395-400.
Li TQ, Aisen AM, Hindmarsh T. Assessment of hepatic iron content using magnetic resonance imaging. Acta Radiol 2004; 45: 119-129.
St. Pierre TG, Clark PR, Chua-anusorn W, Fleming AJ, Jeffrey GP, Olynyk JK, Pootrakul P, Robins E, Linderman R. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005; 105: 855-861.
Wood JC, Enriquez C, Ghugre N, Tyzka JM Carson S, Neslon MD, Coates TD. MRI R2 and R2* mapping accurately estmates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 2005; 106: 1460-1465.
Ghugre NR, Coates TD, Nelson MD, Wood JC. Mechanisms of tissue-iron relaxivity: nuclear magnetic resonance studies of human liver biopsy specimens. Magn Reson Med 2005; 54: 1185-1193.
Brewer CJ, Coates TD, Wood JC. Spleen R2 adn R2* in iron-overloaded patients with sickle cell disease and thalassemia major. J Magn Reson Imag 2009; 29: 357-364.
Hallgren B, Sourander P. The effect of age on the non-haemin iron in the human brain. J Neurochem 1958; 3: 41-51.
Hocq A, Brouette N, Saussez S, Luhmer M, Gillis P, Gossuin Y. Variable-field relaxometry of iron-containing human tissues: a preliminary study. Contrast Media Mol Imag 2009; 4: 157-164.
Dexter DT, Wells FR, Lees AJ, Agig F, Agid Y, Jenner P, Marsden CD. Increased nigral iron content and alterations in other metal ions occuring in brain in Parkinson's disease. J Neurochem 1989; 52: 1830-1836.
Griffiths PD, Dobson BR, Jones GR, Clarke DT. Iron in the basal ganglia in Parkinson's disease: an in vitro study using extended X-ray absorption fine structure and cryoelectron microscopy. Brain 1999; 122: 667-673.
Fischer HW, Van Haverbeke Y, Rinck PA, Schmitz-Feuerhake I, Muller RN. The effect of aging and storage conditions on excised tissues as monitored by longitudinal relaxation dispersion profiles. Magn Reson Med 1989; 9: 315-324.
Clark PR, Chua-Anusorn W, St Pierre TG. Bi-exponential proton transverse relaxation rate(R2) image analysis using RF field intensity-weighted spin density projection: potential for R2 measurement of iron-loaded liver. Magn Reson Imag 2003; 21: 519-530.
Gossuin Y, Burtea C, Monseux A, Toubeau G, Roch A, Muller RN, Gillis P. Ferritin-induced relaxation in tissues: an in vitro study. J Magn Reson Med 2004; 20: 690-696.
Luz Z, Meiboom S. Nuclear magnetic resonance of the protolysis of trimethylammonium ion in aqueous solution. J Chem Phys 1963; 39: 366-370.
Gillis P, Moiny F, Brooks RA. On T-2-shortening by strongly magnetized spheres: a partial refocusing model. Magn Reson Med 2002; 47: 257-263.
Ye FQ, Martin WR, Allen PS. Estimation of brain iron in vivo by means of the interecho time dependence of image contrast. Magn Reson Med 1996; 36: 153-158.
Gossuin Y, Roch A, Muller RN, Gillis P. Relaxation induced by ferritin and ferritin-like magnetic particles: the role of proton exchange. Magn Reson Med 2000; 43: 237-243.
Vuong QL, Gillis P, Gossuin Y. Monte Carlo simulation and theory of proton NMR transverse relaxation induced by aggregation of magnetic particles used as MRI contrast agents. J Magn Reson 2011; 212: 139-148.
Vuong QL, Berret JF, Fresnais J, Gossuin Y, Sandre O. A universal scaling law to predict the efficiency of magnetic nanoparticles as MRI T2-contrast agents. Adv Healthcare Mater 2012; 1: 4-14.
Quintana C, Cowley JM, Marhic C. Electron nanodiffraction and high-resolution electron microscopy studies of the structure and composition of physiological and pathological ferritin. J Struct Biol 2004; 47: 166-178.
Richter GW. A study of hemosiderosis with the aid of electron microscopy. J Exp Med 1957; 106: 203-218.
Richter GW. The cellular transformation of injected colloidal iron complexes into ferritin and hemosiderin in experimental animals: a study with the aid of electron microscopy. J Exp Med 1959; 109: 197-216.
Richter GW. The iron-loaded cell - the cytopathology of iron storage. Am J Pathol 1978; 91: 363-396.
Arstila AU, Bradford WD, Kinney TD, Trump BF. Iron metabolism. Am J Pathol 1970; 58: 419-450.
Iancu TC. Ultrastructural aspects of iron storage, transport and metabolism. J Neural Transm 2011; 118: 329-335.
Kim HS, Joo HJ, Woo JS, Choi YS, Choi SH, Kim H, Moon WK. In vivo magnetic resonance imaging of transgenic mice expressing human ferritin. Mol Imag Biol 2013; 15: 48-57.
Kondo A, Deguchi J, Okado S. Intranuclear iron deposition in hepatocytes and renal tubular cells in mice treated with ferric nitrilotriacetate. Virchows Arch 1998; 433: 543-548.
Sukerkar PA, Rezvi UG, MacRenaris KW, Patel PC, Wood JC, Meade TJ. Polystyrene microsphere-ferritin conjugates: a robust phantom for correlation of relaxivity and size distribution. Magn Reson Med 2011; 65: 522-530.
Jensen JH, Tang H, Tosti CL, Swaminathan SV, Nunez A, Hultman K, Szulc KU, Wu EX, Kim D, Sheth S, Brown TR, Brittenham GM. Separate MRI quantification of dispersed (ferritin-like) and aggregated (hemosiderin-like) storage iron. Magn Reson Med 2010; 63: 1201-1209.
Dezortova M, Herynek V, Krssak M, Kronerwetter C, Trattnig S, Hajek M. Two forms of iron as an intrinsic contrast agent in the basal ganglia of PKAN patients. Contrast Media Mol Imag 2012; 7: 509-515.
Bennett KM, Shapiro EM, Sotak CH, Koretsky AP. Controlled aggregation of ferritin to modulate MRI relaxivity. Biophys J 2008; 95: 342-351.
Ghugre NR, Wood JC. Relaxivity-iron calibration in hepatic iron overload: probing underlying biophysical mechanisms using a Monte Carlo model. Magn Reson Med 2011; 65: 837-847.
