Multiple selected ion monitoring mode for sensitive imaging of eicosanoids in tissues using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry

Nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) enables sensitive label-free mapping of multiple classes of molecules in biological samples. Previously, we demonstrated that combining nano-DESI MSI with selected ion monitoring (SIM) increases the sensitivity of the technique in a narrow m/z range. In this study, we use a series of adjacent multiple SIM (mSIM) windows to acquire nano-DESI MSI data with high sensitivity over a broader m/z range. We demonstrate that this approach substantially improves the quality of imaging data obtained for low-abundance eicosanoids, important lipid mediators derived from eicosapolyenoic acid products of arachidonic acid oxidation. Despite their importance as mediators of inflammation, asthma, fever, pain, hypertension, and stroke, eicosanoids have not been extensively investigated using MSI. This is mainly attributed to their low ionization efficiency and low, subnanomolar, concentrations in tissue, which make it difficult to detect these species in MSI experiments alongside abundant phospholipids. We demonstrate substantial enhancements in the signal-to-noise ratios (S/N) of eicosanoids using imaging in mSIM mode. We have also developed data processing and visualization tools to support this type of MSI data acquisition. S/N enhancements observed in mSIM mode are independent of the properties of analytes making this approach applicable to other low-abundance species in biological and environmental samples.