Quantitative Mapping of Liver Hypoxia in Living Mice Using Time-Resolved Wide-Field Phosphorescence Lifetime Imaging

Abstract

Hypoxia has been identified to contribute the pathogenesis of a wide range of liver diseases, and therefore, quantitative mapping of liver hypoxia is important for providing critical information in the diagnosis and treatment of hepatic diseases. However, the existing imaging methods are unsuitable to quantitatively assess liver hypoxia due to the need of liver-specific contrast agents and be easily affected by other imaging factors. Here, a time-resolved lifetime-based imaging method is established for quantitative mapping of the distribution of hypoxia in the livers of mice by combining a wide-field luminescence lifetime imaging system with an oxygen-sensitive nanoprobe. It is shown that the method is suitable for real-time quantification of the change of oxygen pressure in the process of hepatic ischemia-reperfusion of the mouse. Moreover, the developed lifetime imaging methodology is used to quantitatively map liver hypoxia regions in the mouse model of orthotopic liver tumor, where the average oxygen pressure in tumorous liver is far below the normal liver.