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European Radiology

, Volume 28, Issue 10, pp 4455–4464 | Cite as

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

  • Tobias Getzin
  • Faikah Gueler
  • Björn Hartleben
  • Marcel Gutberlet
  • Anja Thorenz
  • Rongjun Chen
  • Martin Meier
  • Jan Hinrich Bräsen
  • Thorsten Derlin
  • Dagmar Hartung
  • Hannah A. S. Lang
  • Hermann Haller
  • Frank Wacker
  • Song Rong
  • Katja Hueper
Magnetic Resonance

Abstract

Objective

To evaluate Gd-EOB-DTPA-enhanced MRI for quantitative assessment of liver organ damage after hepatic ischaemia reperfusion injury (IRI) in mice.

Methods

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.

Results

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.

Conclusion

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.

Key Points

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.

Keywords

Gadolinium ethoxybenzyl DTPA Magnetic resonance imaging Liver Ischaemia reperfusion injury Mice 

Abbreviations

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

ATP

Adenosine triphosphate

B6

C57Bl/6JHan-ztm

CT

Computed tomography

FLASH

3D-fast low angle shot

Gd-EOB-DTPA

Gadolinium ethoxybenzyl Diethylenetriaminepentaacetic acid

IRI

Ischaemia reperfusion injury

MRI

Magnetic resonance imaging

MRP2

Multidrug resistance-associated protein 2

OATP1

Organic anion-transporting polypeptide 1

PAS

Periodic acid Schiff

SD

Standard deviation

Notes

Acknowledgements

We thank Christian Bergen, Herle Chlebusch and Las Kaehler for their excellent technical support.

Funding

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

Guarantor

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.

Informed consent

Written informed consent was not required for this study because of the nature of the study, which was experimental. No patient data is included.

Ethical approval

Approval from the institutional animal care committee was obtained.

Methodology

• experimental

• performed at one institution

Supplementary material

330_2018_5380_MOESM1_ESM.docx (113 kb)
ESM 1 (DOCX 113 kb)

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Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Tobias Getzin
    • 1
  • Faikah Gueler
    • 2
  • Björn Hartleben
    • 3
  • Marcel Gutberlet
    • 1
  • Anja Thorenz
    • 2
  • Rongjun Chen
    • 2
  • Martin Meier
    • 4
  • Jan Hinrich Bräsen
    • 3
  • Thorsten Derlin
    • 5
  • Dagmar Hartung
    • 1
  • Hannah A. S. Lang
    • 1
  • Hermann Haller
    • 2
  • Frank Wacker
    • 1
  • Song Rong
    • 2
    • 6
  • Katja Hueper
    • 1
  1. 1.Diagnostic and Interventional RadiologyHannover Medical SchoolHannoverGermany
  2. 2.NephrologyHannover Medical SchoolHannoverGermany
  3. 3.PathologyHannover Medical SchoolHannoverGermany
  4. 4.Institue for Laboratory Animal ScienceHannover Medical SchoolHannoverGermany
  5. 5.Nuclear MedicineHannover Medical SchoolHannoverGermany
  6. 6.The Transplantation Center of the Affiliated HospitalZunyi Medical CollegeZunyiChina

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