MRI Measures of Murine Liver Fibrosis

Diana M Lindquist; Elizabeth M Fugate; Jiang Wang; Akanksha Sharma; Chandrashekhar R Gandhi; Jonathan R Dillman

doi:10.1002/jmri.27601

MRI Measures of Murine Liver Fibrosis

J Magn Reson Imaging. 2021 Sep;54(3):739-749. doi: 10.1002/jmri.27601. Epub 2021 Mar 18.

Authors

Diana M Lindquist^{1

2}, Elizabeth M Fugate¹, Jiang Wang³, Akanksha Sharma⁴, Chandrashekhar R Gandhi⁴, Jonathan R Dillman^{1

2}

Affiliations

¹ Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
² Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
³ Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
⁴ Division of Pediatric Gastroenterology, Hepatology & Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

PMID: 33738856
DOI: 10.1002/jmri.27601

Abstract

Background: An imaging method that allows quantitative fibrosis estimates is needed to facilitate the diagnosis of chronic liver disease. Amide proton transfer (APT) and tissue sodium concentration (TSC) estimates could meet this need.

Hypothesis: APT and TSC estimates correlate with fibrosis in a mouse model of chronic liver disease.

Study type: Prospective.

Phantoms/animal model: Male C57Bl/6 mice given CCl₄ or vehicle (N = 8 each) twice weekly for 16 weeks.

Field strength/sequence: Liver T₁ (Look-Locker gradient recalled echo [GRE] sequence), T₂ (multiecho spin echo sequence), T_1rho (fast spin echo sequence with 500 Hz spin locking pulse), and APT (GRE sequence with off-resonance pulses) data were acquired at 7 T at 12 and 16 weeks. Liver sodium data (multiple echo GRE sequence) were acquired at 12 weeks at 9.4 T.

Assessment: Liver proton T₁ , T₂ , T_1rho , APT, sodium T₂ *, and TSC were calculated. Histological measures included Sirius Red, hematoxylin and eosin, liver hydroxyproline content, and serum alanine transaminase (ALT).

Statistical tests: Welch's two-sided t-test was used to test for differences between control and CCl₄ -treated groups for serum ALT, hydroxyproline, Sirius Red staining, T₁ , T₂ , T_1rho , APT, TSC, and sodium T₂ *. Pearson's correlations between liver T₁ , APT, TSC, or sodium T₂ * with Sirius Red staining and hydroxyproline levels were calculated.

Results: APT was significantly different (P < 0.05) between groups in the left liver lobe at 16 weeks (CCl₄ : 8.0% ± 1.2%, controls: 6.2% ± 1.0%), as were average liver TSC at 12 weeks (CCl₄ : 38 mM ± 5 mM, controls: 27 mM ± 2 mM), and average sodium liver T₂ * at 12 weeks (CCl₄ : 10 msec ± 1.0 msec, controls: 12 msec ± 1.9 msec). APT, TSC, and sodium T₂ * correlated significantly (P < 0.05) with Sirius Red staining and hydroxyproline levels.

Data conclusion: Liver TSC and APT significantly correlated with histopathologic markers of fibrosis in this mouse model.

Evidence level: 1 TECHNICAL EFFICACY: Stage 3.

Keywords: amide proton transfer; animal model; liver fibrosis; magnetic resonance imaging; sodium.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Liver / diagnostic imaging
Liver / pathology
Liver Cirrhosis* / diagnostic imaging
Liver Cirrhosis* / pathology
Magnetic Resonance Imaging*
Male
Mice
Phantoms, Imaging
Prospective Studies