Gd-EOB-DTPA-enhanced MRI for quantitative assessment of liver organ damage after partial hepatic ischaemia reperfusion injury: correlation with histology and serum biomarkers of liver cell injury
To evaluate Gd-EOB-DTPA-enhanced MRI for quantitative assessment of liver organ damage after hepatic ischaemia reperfusion injury (IRI) in mice.
Partial hepatic IRI was induced in C57Bl/6 mice (n = 31) for 35, 45, 60 and 90 min. Gd-EOB-DTPA-enhanced MRI was performed 1 day after surgery using a 3D-FLASH sequence. A subgroup of n = 9 animals with 60 min IRI underwent follow-up with MRI and histology 7 days after IRI. The total liver volume was determined by manual segmentation of the entire liver. The volume of functional, contrast-enhanced liver parenchyma was quantified by a region growing algorithm (visual threshold) and an automated segmentation (Otsu’s method). The percentages of functional, contrast-enhanced and damaged non-enhanced parenchyma were calculated according to these volumes. MRI data was correlated with serum liver enzyme concentrations and histologically quantified organ damage using periodic acid–Schiff (PAS) staining.
The percentage of functional (contrasted) liver parenchyma decreased significantly with increasing ischaemia times (control, 94.4 ± 3.3%; 35 min IRI, 89.3 ± 4.1%; 45 min IRI, 87.9 ± 3.3%; 60 min IRI, 68 ± 10.5%, p < 0.001 vs. control; 90 min IRI, 55.9 ± 11.5%, p < 0.001 vs. control). The percentage of non-contrasted liver parenchyma correlated with histologically quantified liver organ damage (r = 0.637, p < 0.01) and serum liver enzyme elevations (AST r = 0.577, p < 0.01; ALT r = 0.536, p < 0.05). Follow-up MRI visualized recovery of functional liver parenchyma (71.5 ± 8.7% vs. 84 ± 2.1%, p < 0.05), consistent with less histological organ damage on day 7.
We demonstrated the feasibility of Gd-EOB-DTPA-enhanced MRI for non-invasive quantification of damaged liver parenchyma following IRI in mice. This novel methodology may refine the characterization of liver disease and could have application in future studies targeting liver organ damage.
• Prolonged ischaemia times in partial liver IRI increase liver organ damage.
• Gd-EOB-DTPA-enhanced MRI at hepatobiliary phase identifies damaged liver volume after hepatic IRI.
• Damaged liver parenchyma quantified with MRI correlates with histological liver damage.
• Hepatobiliary phase Gd-EOB-DTPA-enhanced MRI enables non-invasive assessment of recovery from liver injury.
KeywordsGadolinium ethoxybenzyl DTPA Magnetic resonance imaging Liver Ischaemia reperfusion injury Mice
3D-fast low angle shot
Gadolinium ethoxybenzyl Diethylenetriaminepentaacetic acid
Ischaemia reperfusion injury
Magnetic resonance imaging
Multidrug resistance-associated protein 2
Organic anion-transporting polypeptide 1
Periodic acid Schiff
We thank Christian Bergen, Herle Chlebusch and Las Kaehler for their excellent technical support.
This study has received funding by Hannover Medical School (Junge Akademie Program) as well as REBIRTH Cluster of Excellence of Hannover Medical School.
Compliance with ethical standards
The scientific guarantor of this publication is Dr. Katja Hueper.
Conflict of interest
The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.
Statistics and biometry
No complex statistical methods were necessary for this paper.
Written informed consent was not required for this study because of the nature of the study, which was experimental. No patient data is included.
Approval from the institutional animal care committee was obtained.
• performed at one institution
- 20.Portnoy S, Bishop J, Dazai J et al (2008) Characterization of signal ehnacement following the intraperitoneal injection of gadolinium based contrast agents. Proc 16th Sci Meet Int Soc Magn Reson Med Toronto 54:3206Google Scholar
- 23.Chouker A, Lizak M, Schimel D et al (2008) Comparison of Fenestra VC contrast-enhanced computed tomography imaging with gadopentetate dimeglumine and ferucarbotran magnetic resonance imaging for the in vivo evaluation of murine liver damage after ischaemia and reperfusion. Invest Radiol 43:77–91CrossRefGoogle Scholar