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Automatic Coregistration of High-Resolution MALDI-MSI and Raman Imaging Applied to Cardiac Tissue of Fabry Disease
Johann Dierks1, Eike Ulrich Brockmann1, Anahi-Paula Arias-Loza2
1Leibniz-Institut Für Analytische Wissenschaften─ISAS─e.V., Bunsen-Kirchhoff Straße 11, 44139 Dortmund, Germany.
Analytical Chemistry
|June 4, 2026
Summary
This study introduces a new multimodal imaging technique combining Raman spectroscopy and mass spectrometry imaging to detect molecular changes in tissues. The method successfully identified globotriaosylceramide accumulation in Fabry disease mouse models.
Area of Science:
- Biomedical Imaging
- Molecular Pathology
- Spectroscopy and Mass Spectrometry
Background:
- Early molecular changes in tissues are vital for disease diagnosis and understanding disease mechanisms.
- Conventional methods struggle to detect localized, low-molecular-weight compounds.
- Label-free imaging offers a promising alternative for comprehensive molecular profiling.
Purpose of the Study:
- To establish and validate a multimodal imaging approach integrating Raman spectroscopy and atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-MALDI-MSI).
- To detect and characterize globotriaosylceramide (Gb3) accumulation in cardiac tissue of Fabry disease mouse models.
- To correlate molecular findings with physiological alterations in cardiac tissue.
Main Methods:
- Integration of Raman microscopy (2 μm pixel size) and AP-MALDI-MSI (5 μm pixel size) for label-free molecular profiling of a single tissue section.
- Application to murine models of Fabry disease (GLA knockout and Gb3 synthase overexpression).
- Development of an automated coregistration algorithm for precise overlay of Raman and AP-MALDI-MSI data (5.1 ± 1.6 μm precision).
Main Results:
- Successfully detected heterogeneous globotriaosylceramide (Gb3) lipoform expression in cardiac tissue with high spatial resolution.
- Revealed significantly increased Gb3 content in mice with GLA knockout and Gb3 synthase overexpression compared to controls.
- Identified tissue components like nuclei, collagen, and lipids using Raman microscopy, providing physiological context.
Conclusions:
- The developed multimodal imaging approach enables sensitive and specific detection of molecular alterations in tissues.
- This technique is effective for studying lipid accumulation in genetic diseases like Fabry disease.
- The integration of Raman spectroscopy and AP-MALDI-MSI provides comprehensive molecular and spatial information for disease research.
