Integrating IDEAL‐IQ Sequence with Mass Spectrometry Imaging for Profiling Lipid‐Related Metabolic Reprogramming of Acute Kidney Injury

Abstract To visualize lipid metabolic reprogramming in acute kidney injury (AKI), the iterative decomposition of water and fat with echo asymmetry and least‐squares estimation quantitation (IDEAL‐IQ) is integrated with matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI). Based on PDFF values, triglyceride (TG) are significantly upregulated in the renal medulla of the AKI group. Interestingly, this spatial molecular information is further supplemented with MALDI‐MSI. Meanwhile, the mechanisms underlying TG dysregulation are investigated by assessing mitochondrial morphology, oxidative stress levels, and gene expression using real‐time quantitative PCR analysis. Furthermore, 38 differential lipid molecules, apart from TGs, are successfully screened and identified in the whole kidneys between the control and AKI groups. The biosynthesis of glycerophospholipid is the most obvious metabolic pathway. Moreover, in situ spatial lipid alterations based on the structural heterogeneity are characterized by auto‐segmentation. The downregulation of phosphatidylethanolamine (PE) (e.g., PE 34:2) and upregulation of phosphatidylcholine (PC), phosphatidylserine (PS), and sphingomyelin (SM) are found in the renal cortex from the AKI group. However, in the renal medulla, PC, PS, and SM display remarkable reduction due to the increased vulnerability in this region. Taken together, the findings offer promising insights into the development of a novel diagnostic tool for AKI.