Mass Spectrometry Imaging (MSI) has emerged as a powerful analytical technique, improving the field of spatial omics by providing high-resolution molecular information in biological tissues. We have explored the integration of matrix-assisted laser desorption/ionization (MALDI)-MSI to study the spatial distribution of metabolites and lipids, shedding light on the molecular complexity within the brain, particularly Parkinson’s disease (PD). Key objectives include the development of robust methodologies for the acquisition, processing, and interpretation of spatial omics data. By implementing cuttingedge mass spectrometry technologies and computational approaches, we aim to enhance the sensitivity, specificity, and spatial resolution of MALDI-MSI, enabling the detection and annotation of a wide array of metabolites and lipids with high precision.
We use ultrahigh mass resolution Fourier-transform ion cyclotron resonance (FTICR) MALDI-MSI for the comprehensive mapping of neurotransmitter networks in specific brain regions. We developed a reactive MALDI matrix (FMP-10) to facilitate the covalent charge-tagging of molecules containing phenolic hydroxyl and/or primary or secondary amine groups, including dopaminergic and serotonergic neurotransmitters and their associated metabolites [1,2]. Hence, it improved the detection limit toward lowabundance neurotransmitters and facilitated the simultaneous imaging of neurotransmitter systems in fine structures of the brain. Furthermore, it is challenging to map neuropeptide changes across and within brain regions because of their low in vivo concentrations and complex post-translational processing. Thus, we developed and evaluated a method to image multiple neuropeptides simultaneously in tissue sections [3]. We also established a spatial omics approach that combines histology, MALDI-MSI and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions [4]. The workflow is compatible with commercially available Visium glass slides. The presented approach provides a further level of multimodality when studying small molecules in a tissue context. We illustrated the capabilities of the developed methods on PD brain samples from human post-mortem tissue and animal experimental models.
This study explores the application of MALDI-MSI in elucidating spatial heterogeneity within tissues, emphasizing its potential in biomarker discovery, disease characterization, and understanding the functional implications of metabolite and lipid distributions. The integration of spatial omics data provides a multidimensional perspective, revealing the spatial relationships between molecular species and their biological context.
References:
[1] Shariatgorji et al., Nat Methods. 2019, 16:1021-1028. [2] Shariatgorji et al., Nat Protoc. 2021, 16(7):3298-3321. [3] Hulme et al., Neurobiol Dis. 2020, 137, 104738. [4] Vicari et al., Nat Biotechnol. 2023, doi: 10.1038/s41587-023-01937-y.
