Advancing atherosclerosis research: The Power of lipid imaging with MALDI-MSI

Atherosclerosis is a chronic inflammatory disease that is one of the leading causes of mortality globally. It is characterized by the formation of atheromatous plaques in the intima layer of larger arteries. The (fibro-)fatty plaques usually develop asymptomatically within the vessel until a serious event such as myocardial infarction or stroke occurs. Lipids play a pivotal role in disease progression, but while the causal role of cholesterol is beyond doubt, the distribution of numerous other lipids within the heterogeneous layers of atherosclerotic plaques, and their biological function remain unclear. A deeper understanding of the pathophysiological progression of the disease for prognostics, diagnostics, treatment, and prevention is of great need. Mass spectrometry imaging (MSI), in particular with matrix-assisted laser desorption/ionization (MALDI) offers an unprecedented untargeted characterization of the physiological microenvironment, unraveling the spatial distribution of numerous biochemical compounds. MALDI-MSI offers an advantageous balance of sample preparation, chemical sensitivity, and spatial resolution, and thus has been established as a key technology in modern biomedical analysis. This review focuses on the analysis of lipids in atherosclerotic lesions with MALDI-MSI, for which the past years showed major developments in the spatial characterization of lipids and their interaction within atherosclerotic plaques. We will cover main contributions with a focus on the recent decade, elaborate possibilities, limitations, main findings, and recent developments from sample handling to instrumentation, and estimate current challenges and potentials of MALDI-MSI with respect to a clinical application.