From Tumors to Neurons: Mass Spectrometry Imaging in Spatial Lipidomics

Abstract

Lipids are fundamental biomolecules that regulate cellular structure, energy metabolism, and signaling, and their dysregulation is increasingly implicated in the pathogenesis of cancer and neurological disorders. Although conventional lipidomics has provided valuable insights into global lipid composition, it lacks spatial information essential for understanding tissue-level heterogeneity. Mass spectrometry imaging (MSI) has emerged as a transformative, label-free analytical platform that enables spatially resolved molecular mapping of lipids directly within biological tissues. Utilizing complementary ionization techniques such as matrix-assisted laser desorption/ionization (MALDI), desorption electrospray ionization (DESI), and secondary ion mass spectrometry (SIMS), MSI allows simultaneous detection of hundreds to thousands of lipid species while preserving their two- and three-dimensional spatial context. Recent technological advances have significantly improved spatial resolution, lipid identification, and biological interpretation through integration with multimodal imaging and machine learning approaches. In cancer research, spatial lipidomics have revealed heterogeneous lipid distributions within tumor microenvironments, providing insights into metabolic reprogramming, tumor progression, and therapeutic resistance. In neuroscience, MSI-based neurolipidomics has enabled region-specific characterization of lipid alterations associated with neurodegeneration, neuroinflammation, and myelin pathology. Despite ongoing challenges related to standardization, isomeric lipid discrimination, and data integration, MSI continues to reshape our understanding of lipid biology. This review highlights recent methodological innovations and biological applications of MSI, underscoring its growing impact on spatial lipidomics in cancer and neuroscience.