LIVER

Hepatic ³¹P MRS in rat models of chronic liver disease: assessing the extent and progression of disease

I R Corbin¹, R Buist², J Peeling³, M Zhang⁴, J Uhanova⁴, G Y Minuk¹

¹ Section of Hepatology, Department of Medicine, and Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada
² Department of Radiology, University of Manitoba, Winnipeg, Canada
³ Department of Pharmacology and Therapeutics, and Department of Radiology, University of Manitoba, Winnipeg, Canada
⁴ Section of Hepatology, Department of Medicine, University of Manitoba, Winnipeg, Canada

Correspondence to:
Correspondence to:
Dr G Y Minuk, John Buhler Research Centre, 803F-715 McDermot Ave, Winnipeg, Manitoba R3E 3P4, Canada;
gminuk{at}cc.umanitoba.ca

Background: Hepatic adenosine triphosphate (ATP) levels are an accurate reflection of functioning hepatic mass following surgical resections and acute liver injury.

Objective: To determine whether hepatic ATP levels can serve as a non-invasive means of documenting progression of chronic liver disease to cirrhosis.

Methods: In vivo phosphorus-31 magnetic resonance spectroscopy (³¹P MRS) was performed in three animal models of chronic liver disease. Sixty six adult Sprague- Dawley rats were subjected to either thioacetamide, carbon tetrachloride (CCl₄), or common bile duct ligation (CBDL) to induce liver disease (n=35, 21, and 10, respectively). Serial MRS examinations, blood samples, and liver biopsies (when appropriate) were obtained throughout and/or on completion of the study.

Results: Over the course of the chronic liver disease, a progressive decrease in hepatic ATP levels was consistently observed in each model. The findings were most striking when end stage liver disease (cirrhosis) was established. The reduction in hepatic ATP levels correlated with significant changes in serum albumin concentrations (CCl₄ and CBDL models) and the extent of hepatocyte loss seen histologically (all models).

Conclusion: The results of this study indicate that during progression of chronic liver disease to cirrhosis, there is a progressive reduction in hepatic ATP levels. In addition, changes in hepatic ATP levels correlate with changes in liver function and histology. Thus hepatic ³¹P MRS provides a non-invasive means of documenting the severity and progression of parenchymal and cholestatic models of chronic liver disease in rats.

Keywords: liver; magnetic resonance spectroscopy; liver disease; cirrhosis; rat

Abbreviations: ³¹P-MRS, phosphorus-31 magnetic resonance spectroscopy; ATP, adenosine triphosphate; Pi, inorganic phosphate; PME, phosphomonoesters; PDE, phosphodiesters; TAA, thioacetamide; CCl₄, carbon tetrachloride; CBDL, common bile duct ligation; MDP, methylene diphosphonic acid; ROI, region of interest; TR, repetition time; TE, echo time; FOV, field of view; AST, aspartate aminotransferase; LCAR, liver cell area ratio; PE, phosphoenthaolamine; PC, phosphocholine

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