New Technique Combines Imaging Mass Spectrometry and Microscopy for Enhanced Molecular Visualization

A team of researchers from Vanderbilt University in Nashville, USA, has developed a new approach that combines imaging mass spectrometry (IMS) with microscopy to provide more enhanced and interpretable molecular visualization of tissue samples. The new contour mapping approach allows IMS ion intensity distributions to be combined with stained microscopy images to create more informative molecular contour maps. The team applied this approach to imaging data from Staphylococcus aureus-infected murine kidney and found that contour maps of certain lipids colocalizing with regions of infection provided enhanced visualization of lipid distributions and spatial gradients in and around the bacterial abscess as compared to traditional heatmaps.

Close up microscope equipment for research experiments in science laboratory | Image Credit: © Soonthorn - stock.adobe.com

The researchers also used non-negative matrix factorization (NMF) to group hundreds of individual ion images into a smaller subset of representative patterns. The contour maps of these multivariate NMF images revealed distinct molecular profiles of the major abscesses and surrounding immune response. Moreover, the contour mapping workflow enabled a molecular visualization of the transition zone at the host–pathogen interface, providing potential clues about the spatial molecular dynamics beyond what histological staining alone provides.

NMF is a mathematical technique used to decompose a non-negative matrix into two non-negative matrices, where the product of these matrices approximates the original matrix. NMF is often used in data analysis and machine learning applications, where it can be used to identify patterns and extract features from complex data sets. The technique works by minimizing the difference between the original matrix and the product of the two factor matrices, subject to the constraint that all elements in the matrices must be non-negative. The resulting factor matrices can be used to identify clusters or groups within the data, or to extract meaningful features or components that can be used for further analysis or modeling.

IMS provides untargeted, highly multiplexed maps of molecular distributions in tissue, while microscopy provides greater context. However, heatmaps commonly used to present IMS ion images are limited in their ability to visualize subtle quantitative differences and distribution gradients. Contour mapping, on the other hand, uses information from IMS ion intensity distributions and stained microscopy to create more informative and interpretable molecular contour maps.

In conclusion, the new IMS-based contour mapping approach developed by the team provides an innovative way to augment classical stained microscopy images, providing a more comprehensive and interpretable visualization of IMS-microscopy multimodal molecular imaging data sets. The findings have been published in the Journal of the American Society for Mass Spectrometry (1).

Reference

(1) Sharman, K.; Patterson, N. H.; Migas, L. G.; Neumann, E. K.; Allen, J.; Gibson-Corley, K. N.; Spraggins, J. M.; Van de Plas, R.; Skaar, E. P; Caprioli, R. M. MALDI IMS-Derived Molecular Contour Maps: Augmenting Histology Whole-Slide Images. J. Am. Soc. Mass Spectrom. 2023. DOI: https://doi.org/10.1021/jasms.2c00370