Detection and distribution of sphingolipids in tissue by FTICR MALDI-imaging mass spectrometry

MALDI imaging mass spectrometry is an evolving technology capable of simultaneously profiling multiple analytes of interest across a tissue section and aligning their distribution to tissue histopathology. This chapter summarizes a MALDI imaging workflow for on-tissue identification of sphingolipids and glycosphingolipids using tissues derived from mouse models known to accumulate ceramides (Farber disease) and globotriaosylceramides (Fabry disease). A combination of CID and on-tissue enzyme digestions was utilized for structural confirmation prior to being added to the comprehensive sphingolipid and glycosphingolipid library. Two example case studies related to the modulation of sphingolipid metabolism are provided to illustrate the potential applications of MALDI imaging. In the first case study, distinct ceramides were visualized in relation to Lewis lung carcinoma tumors. In the second case study, tissues were derived from a tumor xenograft model treated with a drug targeting the sphingosine-1-phosphate/ceramide nexus. Representative images of ceramide and hexose ceramides in relation to cancer alone or drug distribution correlating to an increase or decrease in sphingosine-1- phosphate or ceramide species are provided. These MALDI imaging workflows can be readily adapted to assess the distribution of sphingolipids and glycosphingolipids in any tissue system of interest.