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 language | English |
|---|---|
| Pages (from-to) | 724-729 |
| Number of pages | 6 |
| Journal | Magnetic Resonance Imaging |
| Volume | 34 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jul 1 2016 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
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
PY - 2016/7/1
Y1 - 2016/7/1
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.
KW - Dynamic contrast-enhanced-magnetic resonance imaging
KW - Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid
KW - Methionine-choline-deficient (MCD) diet
KW - Mouse
KW - Nonalcoholic steatohepatitis
UR - http://www.scopus.com/inward/record.url?scp=84962690395&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962690395&partnerID=8YFLogxK
U2 - 10.1016/j.mri.2016.03.009
DO - 10.1016/j.mri.2016.03.009
M3 - Article
C2 - 26979540
AN - SCOPUS:84962690395
VL - 34
SP - 724
EP - 729
JO - Magnetic Resonance Imaging
JF - Magnetic Resonance Imaging
SN - 0730-725X
IS - 6
ER -