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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

  • Magnetic Resonance
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European Radiology Aims and scope Submit manuscript

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.

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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

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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.

Author information

Author notes

  1. Tobias Getzin and Faikah Gueler contributed equally

Authors and Affiliations

  1. Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Tobias Getzin, Marcel Gutberlet, Dagmar Hartung, Hannah A. S. Lang, Frank Wacker & Katja Hueper

  2. Nephrology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Faikah Gueler, Anja Thorenz, Rongjun Chen, Hermann Haller & Song Rong

  3. Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Björn Hartleben & Jan Hinrich Bräsen

  4. Institue for Laboratory Animal Science, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Martin Meier

  5. Nuclear Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Thorsten Derlin

  6. The Transplantation Center of the Affiliated Hospital, Zunyi Medical College, Zunyi, China

    Song Rong

Authors
  1. Tobias Getzin
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Corresponding author

Correspondence to Katja Hueper.

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The scientific guarantor of this publication is Dr. Katja Hueper.

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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

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

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Approval from the institutional animal care committee was obtained.

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Getzin, T., Gueler, F., Hartleben, B. et al. 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. Eur Radiol 28, 4455–4464 (2018). https://doi.org/10.1007/s00330-018-5380-8

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  • DOI: https://doi.org/10.1007/s00330-018-5380-8

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