Spatial Mapping of Lipids and Elements by Mass Microscopy and Integration with LA-ICP-MS in the Diabetic Mouse Pancreata

Significance of Topic

Mapping the spatial distribution of lipids and elemental metals in pancreatic tissue provides critical insights into endocrine function and disease mechanisms. High-resolution molecular imaging uncovers local metabolic and elemental signatures that drive islet health and dysfunction, offering potential targets for diabetes research and therapeutic monitoring.

Objectives and Study Overview

This study aimed to integrate mass microscopy imaging of lipids with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to achieve combined molecular and elemental mapping in a transgenic mouse model of diabetes. The model overexpresses mitochondrial ferritin (FtMT) in adipocytes, resulting in pronounced β-cell hyperplasia. By comparing wild-type and FtMT-overexpressing pancreata, the study sought to characterize region-specific lipid profiles and elemental distributions with micrometer-scale resolution.

Methodology and Instrumentation

Frozen mouse pancreatic sections (10 μm) were mounted on In₂O₃-SnO₂ slides.
Matrix application was automated via iMLayer™ using 2-mercaptobenzothiazole (positive mode) and 1,5-diaminonaphthalene (negative mode).
Lipid imaging was performed on the iMScope™ QT mass microscope achieving spatial resolutions down to 5–7 μm. Segmentation and multivariate analyses used IMAGEREVEAL™ MS software.
Elemental imaging utilized an imageBIO266 laser ablation system coupled to an ICPMS-2030, providing 5–50 μm resolution elemental maps.

Main Results and Discussion

Unsupervised segmentation of MALDI images distinguished islet core, α-cell regions, exocrine tissue, and vasculature. Principal component and VIP analyses identified phosphatidylcholines and sphingomyelins (e.g., SM 34:1;O₂) with significant variation across zones. FtMT-overexpressing pancreata exhibited altered lipid signatures in hyperplastic islets compared to controls.
LA-ICP-MS revealed zinc accumulation in islets, iron localization in blood vessels, and ubiquitous phosphorus. Hyperplastic islets in transgenic mice showed increased Zn signal correlating with enhanced insulin production.

Benefits and Practical Applications

• Label-free, in situ molecular imaging preserves tissue architecture and basal metabolite levels.
• Combined lipid and elemental maps enable correlation of metabolic and trace metal signatures in disease states.
• High spatial resolution enhances detection of cell-type specific biomarkers for QA/QC and preclinical studies.

Future Trends and Opportunities

Advancements may include integration with single-cell transcriptomics, deeper multiplexing of lipid classes, and clinical translation to human biopsies. Improvements in laser optics and mass analyzer sensitivity will push sub-micrometer mapping. Combining imaging modalities promises comprehensive multi-omic atlases of tissues.

Conclusion

This integrated mass microscopy and LA-ICP-MS approach delivers a powerful platform for spatially resolved lipidomics and metallomics in pancreatic research. The methodology uncovers region-specific molecular changes in diabetic models, with broad applications in disease profiling and drug development.

Reference

• Ye J. et al. Journal of Clinical Investigation, 2018;128(3):1178–1189.
• Kusminski C.M. et al. Diabetes, 2020;69(3):313–330.
• MetaboAnalyst 5.0, www.metaboanalyst.ca.