Evaluation of combined workflows for multimodal mass spectrometry imaging of elements and lipids from the same tissue section

Anal Bioanal Chem. 2025 Jan 20. doi: 10.1007/s00216-024-05696-w. Online ahead of print.

Abstract

The wide range of mass spectrometry imaging (MSI) technologies enables the spatial distributions of many analyte classes to be investigated. However, as each approach is best suited to certain analytes, combinations of different MSI techniques are increasingly being explored to obtain more chemical information from a sample. In many cases, performing a sequential analysis of the same tissue section is ideal to enable a direct correlation of multimodal data. In this work, we explored different workflows that allow sequential lipid and elemental imaging on the same tissue section using atmospheric pressure laser desorption/ionisation-plasma post-ionisation-MSI (AP-MALDI-PPI-MSI) and laser ablation-inductively coupled plasma-MSI (LA-ICP-MSI), respectively. It is found that performing lipid imaging first using matrix-coated samples, followed by elemental imaging on matrix-coated samples, provides high-quality MSI datasets for both lipids and elements, with the resulting distributions being similar to those obtained when each is performed in isolation. The effect of matrix removal prior to elemental imaging, and of performing elemental imaging first were also investigated but found to generally yield lower quality elemental imaging data but comparable lipid imaging data. Finally, we used the ability to acquire both elemental and lipid imaging data from the same section to investigate the spatial correlations between different lipids (including ceramides, phosphatidylethanolamine, and hexosylceramides) and elements within mouse brain tissue.

Keywords: Elemental analysis; Lipid analysis; Mass spectrometry imaging; Multimodal imaging; Single tissue section.