European Society of Toxicologic Pathology-Pathology 2.0 Mass Spectrometry Imaging Special Interest Group: Mass Spectrometry Imaging in Diagnostic and Toxicologic Pathology for Label-Free Detection of Molecules-From Basics to Practical Applications

Mass Spectrometry Imaging (MSI) is a powerful tool to understand molecular pathophysiology and therapeutic and toxicity mechanisms, as well as for patient stratification and precision medicine. MSI, a label-free technique offering detailed spatial information on a large number of molecules in different tissues, encompasses various techniques including Matrix-Assisted Laser Desorption Ionization (MALDI), Desorption Electrospray Ionization (DESI), and Secondary Ion Mass Spectrometry (SIMS) that can be applied in diagnostic and toxicologic pathology. Given the utmost importance of high-quality samples, pathologists play a pivotal role in providing comprehensive pathobiology and histopathology knowledge, as well as information on tissue sampling, orientation, morphology, endogenous biomarkers, and pathogenesis, which are crucial for the correct interpretation of targeted experiments. This article introduces MSI and its fundamentals, and reports on case examples, determining the best suited technology to address research questions. High-level principles and characteristics of the most used modalities for spatial metabolomics, lipidomics and proteomics, sensitivity and specific requirements for sample procurement and preparation are discussed. MSI applications for projects focused on drug metabolism, nonclinical safety assessment, and pharmacokinetics/pharmacodynamics and various diagnostic pathology cases from nonclinical and clinical settings are showcased.