Special Section on Fluorescence Molecular Imaging Honoring Prof. Roger Tsien, a Pioneer in Biomedical Optics

Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury

[+] Author Affiliations
Camilla A. Thorling, Michael S. Roberts

University of South Australia, School of Pharmacy and Medical Science, City East Campus, Adelaide, South Australia 5000, Australia

University of Queensland, Therapeutics Research Centre, School of Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia

Xin Liu, Washington Y. Sanchez

University of Queensland, Therapeutics Research Centre, School of Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia

Frank J. Burczynski

University of Manitoba, Faculty of Pharmacy, Winnipeg, Manitoba R3E0T5, Canada

Linda M. Fletcher

Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Brisbane, Queensland 4102, Australia

J. Biomed. Opt. 18(10), 101306 (Jun 28, 2013). doi:10.1117/1.JBO.18.10.101306
History: Received December 28, 2012; Revised May 23, 2013; Accepted May 23, 2013
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Abstract.  The liver is important in the biotransformation of various drugs, where hepatic transporters facilitate uptake and excretion. Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery, and the developing oxidative stress can lead to graft failure. We used intravital multiphoton tomography, with fluorescence lifetime imaging, to characterize metabolic damage associated with hepatic I/R injury and to model the distribution of fluorescein as a measure of liver function. In addition to measuring a significant increase in serum alanine transaminase levels, characteristic of hepatic I/R injury, a decrease in the averaged weighted lifetime of reduced nicotinamide adenine dinucleotide phosphate was observed, which can be attributed to a changed metabolic redox state of the hepatocytes. I/R injury was associated with delayed uptake and excretion of fluorescein and elevated area-under-the-curve within the hepatocytes compared to sham (i.e., untreated control) as visualized and modeled using images recorded by intravital multiphoton tomography. High-performance liquid chromatography analysis showed no differences in plasma or bile concentrations of fluorescein. Finally, altered fluorescein distribution was associated with acute changes in the expression of liver transport proteins. In summary, multiphoton intravital imaging is an effective approach to measure liver function and is more sensitive in contrasting the impact of I/R injury than measuring plasma and bile concentrations of fluorescein.

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© 2013 Society of Photo-Optical Instrumentation Engineers

Citation

Camilla A. Thorling ; Xin Liu ; Frank J. Burczynski ; Linda M. Fletcher ; Michael S. Roberts, et al.
"Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury", J. Biomed. Opt. 18(10), 101306 (Jun 28, 2013). ; http://dx.doi.org/10.1117/1.JBO.18.10.101306


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