Spatial Profiling of Elements through Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) is widely used for biomolecular mapping but has not been extensively applied for direct element imaging. Established techniques such as LA-ICP-MS and SIMS provide high sensitivity for elemental analysis but lack the ability to simultaneously map elements and biomolecules. Here, we demonstrate the feasibility of MALDI MSI for direct spatial element profiling across multiple biological contexts. We optimized MALDI MSI parameters─including laser power, ionization conditions, and mass resolving power─to enable the detection of endogenous and exogenous elements such as Fe, Ca, Gd, Pt, and Cl. Using a combination of high-resolution FTICR-MS and timsTOF MSI, we assessed ionization efficiency, spectral fidelity, and isotopic accuracy. The method was applied to murine developmental models, genetic metal accumulation disorders, and platinum-based chemotherapy distributions in tumors. Our results demonstrate that MALDI MSI enables element detection while preserving spatial integrity. Computational modeling and spectral similarity analysis confirmed the reliability of isotopologue distributions. These findings establish MALDI MSI as a viable alternative for high-resolution element imaging, offering a complementary approach to LA-ICP-MS and SIMS by integrating atomic and biomolecular spatial distributions. This method expands the analytical capabilities of MALDI MSI and opens new avenues for metallomics, pharmacokinetics, and disease biomarker research.