Skip to main content
Top
Published in: Magnetic Resonance Materials in Physics, Biology and Medicine 3/2013

01-06-2013 | Research Article

Delayed hepatic signal recovery on ferucarbotran-enhanced magnetic resonance images: an experimental study in rat livers with gadolinium chloride-induced Kupffer cell damage

Authors: Toshihiro Furuta, Masayuki Yamaguchi, Ryutaro Nakagami, Masaaki Akahane, Manabu Minami, Kuni Ohtomo, Noriyuki Moriyama, Hirofumi Fujii

Published in: Magnetic Resonance Materials in Physics, Biology and Medicine | Issue 3/2013

Login to get access

Abstract

Objective

Hepatic signal recovery, rather than reduction, in ferucarbotran-enhanced magnetic resonance imaging (MRI) is a potential diagnostic marker of liver damage. We investigated hepatic signal recovery in rats with gadolinium chloride (GdCl3)-induced Kupffer cell (KC) damage.

Materials and methods

Twelve rats received 8 μmol iron/kg of ferucarbotran 1 day after 0–7.5 mg/kg GdCl3 injection (experiment A). Another 12 rats received ferucarbotran followed by GdCl3 injection 6 h later (experiment B). In each experiment, three rats without GdCl3 (“no injury group”) served as control. Another six rats received GdCl3 alone without ferucarbotran. Hepatic signals were assessed on T 2 * -weighted images for up to 29 days. Iron deposits were histologically examined on day 29.

Results

Hepatic signal recovery was delayed in a GdCl3 dose-dependent manner in experiment A. Gadolinium chloride alone reduced hepatic signal 15 % during this experiment. Hepatic signal recovery was delayed only in rats that received 7.5 mg/kg GdCl3 in experiment B. Hepatic signals negatively correlated with iron deposits in KCs and hepatocytes.

Conclusion

Hepatic signal recovery on ferucarbotran-enhanced MRI was delayed in the context of GdCl3-induced KC damage due to increased hepatic iron deposits. Hepatic signal recovery may be used as a clinical marker of KC damage in liver disorders, including radiation-induced hepatitis.
Literature
1.
go back to reference Lawaczeck R, Bauer H, Frenzel T, Hasegawa M, Ito Y, Kito K, Miwa N, Tsutsui H, Vogler H, Weinmann HJ (1997) Magnetic iron oxide particles coated with carboxydextran for parenteral administration and liver contrasting. Pre-clinical profile of SH U555A. Acta Radiol 38:584–597PubMed Lawaczeck R, Bauer H, Frenzel T, Hasegawa M, Ito Y, Kito K, Miwa N, Tsutsui H, Vogler H, Weinmann HJ (1997) Magnetic iron oxide particles coated with carboxydextran for parenteral administration and liver contrasting. Pre-clinical profile of SH U555A. Acta Radiol 38:584–597PubMed
2.
go back to reference Kato N, Ihara S, Tsujimoto T, Miyazawa T (2002) Effect of resovist on rats with different severities of liver cirrhosis. Invest Radiol 37:292–298PubMedCrossRef Kato N, Ihara S, Tsujimoto T, Miyazawa T (2002) Effect of resovist on rats with different severities of liver cirrhosis. Invest Radiol 37:292–298PubMedCrossRef
3.
go back to reference Clement O, Muhler A, Vexler VS, Rosenau W, Berthezene Y, Kuwatsuru R, Brasch RC (1992) Evaluation of radiation-induced liver injury with MR imaging: comparison of hepatocellular and reticuloendothelial contrast agents. Radiology 185:163–168PubMed Clement O, Muhler A, Vexler VS, Rosenau W, Berthezene Y, Kuwatsuru R, Brasch RC (1992) Evaluation of radiation-induced liver injury with MR imaging: comparison of hepatocellular and reticuloendothelial contrast agents. Radiology 185:163–168PubMed
4.
go back to reference Tomita K, Tanimoto A, Irie R, Kikuchi M, Yokoyama H, Teratani T, Suzuki T, Taguchi T, Noguchi M, Ohkura T, Hibi T (2008) Evaluating the severity of nonalcoholic steatohepatitis with superparamagnetic iron oxide-enhanced magnetic resonance imaging. J Magn Reson Imaging 28:1444–1450PubMedCrossRef Tomita K, Tanimoto A, Irie R, Kikuchi M, Yokoyama H, Teratani T, Suzuki T, Taguchi T, Noguchi M, Ohkura T, Hibi T (2008) Evaluating the severity of nonalcoholic steatohepatitis with superparamagnetic iron oxide-enhanced magnetic resonance imaging. J Magn Reson Imaging 28:1444–1450PubMedCrossRef
5.
go back to reference Tanimoto A, Oshio K, Suematsu M, Pouliquen D, Stark DD (2001) Relaxation effects of clustered particles. J Magn Reson Imaging 14:72–77PubMedCrossRef Tanimoto A, Oshio K, Suematsu M, Pouliquen D, Stark DD (2001) Relaxation effects of clustered particles. J Magn Reson Imaging 14:72–77PubMedCrossRef
6.
go back to reference Tanimoto A, Yuasa Y, Shinmoto H, Jinzaki M, Imai Y, Okuda S, Kuribayashi S (2002) Superparamagnetic iron oxide-mediated hepatic signal intensity change in patients with and without cirrhosis: pulse sequence effects and Kupffer cell function. Radiology 222:661–666PubMedCrossRef Tanimoto A, Yuasa Y, Shinmoto H, Jinzaki M, Imai Y, Okuda S, Kuribayashi S (2002) Superparamagnetic iron oxide-mediated hepatic signal intensity change in patients with and without cirrhosis: pulse sequence effects and Kupffer cell function. Radiology 222:661–666PubMedCrossRef
7.
go back to reference Mori K, Fukuda K, Asaoka H, Ueda T, Kunimatsu A, Okamoto Y, Nasu K, Fukunaga K, Morishita Y, Minami M (2009) Radiofrequency ablation of the liver: determination of ablative margin at MR imaging with impaired clearance of ferucarbotran—feasibility study. Radiology 251:557–565PubMedCrossRef Mori K, Fukuda K, Asaoka H, Ueda T, Kunimatsu A, Okamoto Y, Nasu K, Fukunaga K, Morishita Y, Minami M (2009) Radiofrequency ablation of the liver: determination of ablative margin at MR imaging with impaired clearance of ferucarbotran—feasibility study. Radiology 251:557–565PubMedCrossRef
8.
go back to reference Hardonk MJ, Dijkhuis FW, Hulstaert CE, Koudstaal J (1992) Heterogeneity of rat liver and spleen macrophages in gadolinium chloride-induced elimination and repopulation. J Leukoc Biol 52:296–302PubMed Hardonk MJ, Dijkhuis FW, Hulstaert CE, Koudstaal J (1992) Heterogeneity of rat liver and spleen macrophages in gadolinium chloride-induced elimination and repopulation. J Leukoc Biol 52:296–302PubMed
9.
go back to reference Ide M, Kuwamura M, Kotani T, Sawamoto O, Yamate J (2005) Effects of gadolinium chloride (GdCl3) on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions. J Comp Pathol 133:92–102PubMedCrossRef Ide M, Kuwamura M, Kotani T, Sawamoto O, Yamate J (2005) Effects of gadolinium chloride (GdCl3) on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions. J Comp Pathol 133:92–102PubMedCrossRef
10.
go back to reference Lee CM, Yeoh GC, Olynyk JK (2004) Differential effects of gadolinium chloride on Kupffer cells in vivo and in vitro. Int J Biochem Cell Biol 36:481–488PubMedCrossRef Lee CM, Yeoh GC, Olynyk JK (2004) Differential effects of gadolinium chloride on Kupffer cells in vivo and in vitro. Int J Biochem Cell Biol 36:481–488PubMedCrossRef
11.
go back to reference Ding H, Peng R, Reed E, Li QQ (2003) Effects of Kupffer cell inhibition on liver function and hepatocellular activity in mice. Int J Mol Med 12:549–557PubMed Ding H, Peng R, Reed E, Li QQ (2003) Effects of Kupffer cell inhibition on liver function and hepatocellular activity in mice. Int J Mol Med 12:549–557PubMed
12.
go back to reference Ruttinger D, Vollmar B, Wanner GA, Messmer K (1996) In vivo assessment of hepatic alterations following gadolinium chloride-induced Kupffer cell blockade. J Hepatol 25:960–967PubMedCrossRef Ruttinger D, Vollmar B, Wanner GA, Messmer K (1996) In vivo assessment of hepatic alterations following gadolinium chloride-induced Kupffer cell blockade. J Hepatol 25:960–967PubMedCrossRef
13.
go back to reference Wasserman AJ, Monticello TM, Feldman RS, Gitlitz PH, Durham SK (1996) Utilization of electron probe microanalysis in gadolinium-treated mice. Toxicol Pathol 24:588–594PubMedCrossRef Wasserman AJ, Monticello TM, Feldman RS, Gitlitz PH, Durham SK (1996) Utilization of electron probe microanalysis in gadolinium-treated mice. Toxicol Pathol 24:588–594PubMedCrossRef
14.
go back to reference Spencer AJ, Wilson SA, Batchelor J, Reid A, Rees J, Harpur E (1997) Gadolinium chloride toxicity in the rat. Toxicol Pathol 25:245–255PubMedCrossRef Spencer AJ, Wilson SA, Batchelor J, Reid A, Rees J, Harpur E (1997) Gadolinium chloride toxicity in the rat. Toxicol Pathol 25:245–255PubMedCrossRef
15.
go back to reference Spencer A, Wilson S, Harpur E (1998) Gadolinium chloride toxicity in the mouse. Hum Exp Toxicol 17:633–637PubMedCrossRef Spencer A, Wilson S, Harpur E (1998) Gadolinium chloride toxicity in the mouse. Hum Exp Toxicol 17:633–637PubMedCrossRef
16.
go back to reference Adding LC, Bannenberg GL, Gustafsson LE (2001) Basic experimental studies and clinical aspects of gadolinium salts and chelates. Cardiovasc Drug Rev 19:41–56PubMedCrossRef Adding LC, Bannenberg GL, Gustafsson LE (2001) Basic experimental studies and clinical aspects of gadolinium salts and chelates. Cardiovasc Drug Rev 19:41–56PubMedCrossRef
17.
go back to reference Nelson JE, Wilson L, Brunt EM, Yeh MM, Kleiner DE, Unalp-Arida A, Kowdley KV (2011) Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease. Hepatology 53:448–457PubMedCrossRef Nelson JE, Wilson L, Brunt EM, Yeh MM, Kleiner DE, Unalp-Arida A, Kowdley KV (2011) Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease. Hepatology 53:448–457PubMedCrossRef
18.
go back to reference Fabre M, Leroy-Willig A, Denis CV, Ba N, Schoevaert D, Guettier C, Geldwerth-Feniger D (2010) In vivo MRI and ex vivo quantification of iron and Kupffer cells demonstrate residual phagocytic activity in mouse liver after a gadolinium chloride injection. Biochimie 92:1343–1353PubMedCrossRef Fabre M, Leroy-Willig A, Denis CV, Ba N, Schoevaert D, Guettier C, Geldwerth-Feniger D (2010) In vivo MRI and ex vivo quantification of iron and Kupffer cells demonstrate residual phagocytic activity in mouse liver after a gadolinium chloride injection. Biochimie 92:1343–1353PubMedCrossRef
19.
go back to reference Moriconi F, Ahmad G, Ramadori P, Malik I, Sheikh N, Merli M, Riggio O, Dudas J, Ramadori G (2009) Phagocytosis of gadolinium chloride or zymosan induces simultaneous upregulation of hepcidin- and downregulation of hemojuvelin- and Fpn-1-gene expression in murine liver. Lab Invest 89:1252–1260PubMedCrossRef Moriconi F, Ahmad G, Ramadori P, Malik I, Sheikh N, Merli M, Riggio O, Dudas J, Ramadori G (2009) Phagocytosis of gadolinium chloride or zymosan induces simultaneous upregulation of hepcidin- and downregulation of hemojuvelin- and Fpn-1-gene expression in murine liver. Lab Invest 89:1252–1260PubMedCrossRef
20.
go back to reference Damoiseaux JG, Dopp EA, Calame W, Chao D, MacPherson GG, Dijkstra CD (1994) Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 83:140–147PubMed Damoiseaux JG, Dopp EA, Calame W, Chao D, MacPherson GG, Dijkstra CD (1994) Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 83:140–147PubMed
21.
go back to reference Dijkstra CD, Dopp EA, Joling P, Kraal G (1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 54:589–599PubMed Dijkstra CD, Dopp EA, Joling P, Kraal G (1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 54:589–599PubMed
Metadata
Title
Delayed hepatic signal recovery on ferucarbotran-enhanced magnetic resonance images: an experimental study in rat livers with gadolinium chloride-induced Kupffer cell damage
Authors
Toshihiro Furuta
Masayuki Yamaguchi
Ryutaro Nakagami
Masaaki Akahane
Manabu Minami
Kuni Ohtomo
Noriyuki Moriyama
Hirofumi Fujii
Publication date
01-06-2013
Publisher
Springer-Verlag
Published in
Magnetic Resonance Materials in Physics, Biology and Medicine / Issue 3/2013
Print ISSN: 0968-5243
Electronic ISSN: 1352-8661
DOI
https://doi.org/10.1007/s10334-012-0354-3

Other articles of this Issue 3/2013

Magnetic Resonance Materials in Physics, Biology and Medicine 3/2013 Go to the issue