Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice

Tomomi Yamada, Atsushi Obata, Yuto Kashiwagi, Takemi Rokugawa, Shuuichi Matsushima, Tadateru Hamada, Hiroshi Watabe, Koji Abe

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Objective: The purpose of this study is to investigate the correlation between the liver kinetics of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and liver histopathology in a mouse model of NASH by using dynamic contrast-enhanced MRI. Materials and methods: Twenty male C57/BL6 mice aged 8 weeks were fed a methionine-choline-deficient (MCD) diet for 2, 4 and 6 weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6 weeks after the MCD feeding. The signal intensity of the liver was obtained from dynamic MR images and relative enhancement (RE), and the time to maximum RE (Tmax) and half-life of elimination RE (T1/2) were calculated. After MRI scan, histopathological scores of hepatic steatosis and inflammation and blood biochemistry data, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were obtained. Results: Plasma AST and ALT levels were significantly increased in mice fed MCD. Histopathological scores indicated that steatohepatitis progressed with the MCD feeding period from 2 to 6 weeks, but significant fibrosis was observed only in mice fed MCD for 6 weeks. Gd-EOB-DTPA-enhanced MRI showed that Tmax was significantly prolonged in the livers of the 6-week group compared to the control group (control, 4.0 ± 0.7 min; MCD 6w, 12.1 ± 1.6 min), although there was no alteration in the 2- and 4-week groups. T1/2 was significantly prolonged in mice fed MCD for 4 and 6 weeks compared to the control group (control, 19.9 ± 2.0 min; MCD 4w, 46.7 ± 8.7 min; MCD 6w, 65.4 ± 8.8 min). The parameters of Gd-EOB-DTPA kinetics (Tmax and T1/2) in the liver were positively correlated with the liver histopathological score (steatosis vs Tmax, rho = 0.69, P = 0.0007; inflammation vs Tmax, rho = 0.66, P = 0.00155; steatosis vs T1/2, rho = 0.77, P <0.0001; inflammation vs T1/2, rho = 0.73, P = 0.0003). Conclusions: The liver kinetics of Gd-EOB-DTPA correlated well with the inflammation score in the mouse model of NASH, suggesting the possibility of detecting the steatohepatitis stage without fibrosis by Gd-EOB-DTPA-enhanced MR imaging.

Original languageEnglish
Pages (from-to)724-729
Number of pages6
JournalMagnetic Resonance Imaging
Volume34
Issue number6
DOIs
Publication statusPublished - Jul 1 2016
Externally publishedYes

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Pentetic Acid
Gadolinium
Choline
Methionine
Liver
Inflammation
Imaging techniques
Acids
Fatty Liver
Aspartate Aminotransferases
Alanine Transaminase
Magnetic resonance imaging
Kinetics
Fibrosis
Non-alcoholic Fatty Liver Disease
Image Enhancement
Control Groups
Biochemistry
Nutrition
Half-Life

Keywords

  • Dynamic contrast-enhanced-magnetic resonance imaging
  • Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid
  • Methionine-choline-deficient (MCD) diet
  • Mouse
  • Nonalcoholic steatohepatitis

ASJC Scopus subject areas

  • Biophysics
  • Radiology Nuclear Medicine and imaging
  • Biomedical Engineering

Cite this

Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice. / Yamada, Tomomi; Obata, Atsushi; Kashiwagi, Yuto; Rokugawa, Takemi; Matsushima, Shuuichi; Hamada, Tadateru; Watabe, Hiroshi; Abe, Koji.

In: Magnetic Resonance Imaging, Vol. 34, No. 6, 01.07.2016, p. 724-729.

Research output: Contribution to journalArticle

Yamada, T, Obata, A, Kashiwagi, Y, Rokugawa, T, Matsushima, S, Hamada, T, Watabe, H & Abe, K 2016, 'Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice', Magnetic Resonance Imaging, vol. 34, no. 6, pp. 724-729. https://doi.org/10.1016/j.mri.2016.03.009
Yamada, Tomomi ; Obata, Atsushi ; Kashiwagi, Yuto ; Rokugawa, Takemi ; Matsushima, Shuuichi ; Hamada, Tadateru ; Watabe, Hiroshi ; Abe, Koji. / Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice. In: Magnetic Resonance Imaging. 2016 ; Vol. 34, No. 6. pp. 724-729.
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T1 - Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice

AU - Yamada, Tomomi

AU - Obata, Atsushi

AU - Kashiwagi, Yuto

AU - Rokugawa, Takemi

AU - Matsushima, Shuuichi

AU - Hamada, Tadateru

AU - Watabe, Hiroshi

AU - Abe, Koji

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N2 - Objective: The purpose of this study is to investigate the correlation between the liver kinetics of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and liver histopathology in a mouse model of NASH by using dynamic contrast-enhanced MRI. Materials and methods: Twenty male C57/BL6 mice aged 8 weeks were fed a methionine-choline-deficient (MCD) diet for 2, 4 and 6 weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6 weeks after the MCD feeding. The signal intensity of the liver was obtained from dynamic MR images and relative enhancement (RE), and the time to maximum RE (Tmax) and half-life of elimination RE (T1/2) were calculated. After MRI scan, histopathological scores of hepatic steatosis and inflammation and blood biochemistry data, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were obtained. Results: Plasma AST and ALT levels were significantly increased in mice fed MCD. Histopathological scores indicated that steatohepatitis progressed with the MCD feeding period from 2 to 6 weeks, but significant fibrosis was observed only in mice fed MCD for 6 weeks. Gd-EOB-DTPA-enhanced MRI showed that Tmax was significantly prolonged in the livers of the 6-week group compared to the control group (control, 4.0 ± 0.7 min; MCD 6w, 12.1 ± 1.6 min), although there was no alteration in the 2- and 4-week groups. T1/2 was significantly prolonged in mice fed MCD for 4 and 6 weeks compared to the control group (control, 19.9 ± 2.0 min; MCD 4w, 46.7 ± 8.7 min; MCD 6w, 65.4 ± 8.8 min). The parameters of Gd-EOB-DTPA kinetics (Tmax and T1/2) in the liver were positively correlated with the liver histopathological score (steatosis vs Tmax, rho = 0.69, P = 0.0007; inflammation vs Tmax, rho = 0.66, P = 0.00155; steatosis vs T1/2, rho = 0.77, P <0.0001; inflammation vs T1/2, rho = 0.73, P = 0.0003). Conclusions: The liver kinetics of Gd-EOB-DTPA correlated well with the inflammation score in the mouse model of NASH, suggesting the possibility of detecting the steatohepatitis stage without fibrosis by Gd-EOB-DTPA-enhanced MR imaging.

AB - Objective: The purpose of this study is to investigate the correlation between the liver kinetics of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and liver histopathology in a mouse model of NASH by using dynamic contrast-enhanced MRI. Materials and methods: Twenty male C57/BL6 mice aged 8 weeks were fed a methionine-choline-deficient (MCD) diet for 2, 4 and 6 weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6 weeks after the MCD feeding. The signal intensity of the liver was obtained from dynamic MR images and relative enhancement (RE), and the time to maximum RE (Tmax) and half-life of elimination RE (T1/2) were calculated. After MRI scan, histopathological scores of hepatic steatosis and inflammation and blood biochemistry data, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were obtained. Results: Plasma AST and ALT levels were significantly increased in mice fed MCD. Histopathological scores indicated that steatohepatitis progressed with the MCD feeding period from 2 to 6 weeks, but significant fibrosis was observed only in mice fed MCD for 6 weeks. Gd-EOB-DTPA-enhanced MRI showed that Tmax was significantly prolonged in the livers of the 6-week group compared to the control group (control, 4.0 ± 0.7 min; MCD 6w, 12.1 ± 1.6 min), although there was no alteration in the 2- and 4-week groups. T1/2 was significantly prolonged in mice fed MCD for 4 and 6 weeks compared to the control group (control, 19.9 ± 2.0 min; MCD 4w, 46.7 ± 8.7 min; MCD 6w, 65.4 ± 8.8 min). The parameters of Gd-EOB-DTPA kinetics (Tmax and T1/2) in the liver were positively correlated with the liver histopathological score (steatosis vs Tmax, rho = 0.69, P = 0.0007; inflammation vs Tmax, rho = 0.66, P = 0.00155; steatosis vs T1/2, rho = 0.77, P <0.0001; inflammation vs T1/2, rho = 0.73, P = 0.0003). Conclusions: The liver kinetics of Gd-EOB-DTPA correlated well with the inflammation score in the mouse model of NASH, suggesting the possibility of detecting the steatohepatitis stage without fibrosis by Gd-EOB-DTPA-enhanced MR imaging.

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KW - Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid

KW - Methionine-choline-deficient (MCD) diet

KW - Mouse

KW - Nonalcoholic steatohepatitis

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