Mass spectrometry imaging for spatially resolved multi-omics molecular mapping

Bressan, D., Battistoni, G. & Hannon, G. J. The dawn of spatial omics. Science 381. https://doi.org/10.1126/science.abq4964 (2023).Vandereyken, K., Sifrim, A., Thienpont, B. & Voet, T. Methods and applications for single-cell and spatial multi-omics. Nat. Rev. Genet. 24, 494–515 (2023).Article 
CAS 
PubMed 

Google Scholar 
Babu, M. & Snyder, M. Multi-omics profiling for health. Mol. Cell. Proteom. 22. https://doi.org/10.1016/j.mcpro.2023.100561 (2023).Wagner, A., Regev, A. & Yosef, N. Revealing the vectors of cellular identity with single-cell genomics. Nat. Biotechnol. 34, 1145–1160 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Tian, L. Y., Chen, F. & Macosko, E. Z. The expanding vistas of spatial transcriptomics. Nat. Biotechnol. 41, 773–782 (2023).Article 
CAS 
PubMed 

Google Scholar 
Zhang, H., Delafield, D. G. & Li, L. J. Mass spectrometry imaging: the rise of spatially resolved single-cell omics. Nat. Methods 20, 327–330 (2023).Article 
CAS 
PubMed 

Google Scholar 
Akbari, B., Huber, B. R. & Sherman, J. H. Unlocking the hidden depths: multi-modal integration of imaging mass spectrometry-based and molecular imaging techniques. Critic. Rev. Anal. Chem. https://doi.org/10.1080/10408347.2023.2266838 (2023).Crosetto, N., Bienko, M. & van Oudenaarden, A. Spatially resolved transcriptomics and beyond. Nat. Rev. Genet. 16, 57–66 (2015).Article 
CAS 
PubMed 

Google Scholar 
Hsieh, W. C. et al. Spatial multi-omics analyses of the tumor immune microenvironment. J. Biomed. Sci. 29. https://doi.org/10.1186/s12929-022-00879-y (2022).Zhang, H. et al. Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging. Nat. Commun. 14. https://doi.org/10.1038/s41467-023-40512-6 (2023).Bien, T., Koerfer, K., Schwenzfeier, J., Dreisewerd, K. & Soltwisch, J. Mass spectrometry imaging to explore molecular heterogeneity in cell culture. Proc. Natl Acad. Sci. USA 119, e2114365119 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Merdas, M. et al. On-tissue chemical derivatization reagents for matrix-assisted laser desorption/ionization mass spectrometry imaging. J. Mass Spectrom. 56. https://doi.org/10.1002/jms.4731 (2021).Harkin, C. et al. On-tissue chemical derivatization in mass spectrometry imaging. Mass Spectrom. Rev. 41, 662–694 (2022).Article 
CAS 
PubMed 

Google Scholar 
Lu, H. Y., Zhang, H. & Li, L. J. Chemical tagging mass spectrometry: an approach for single-cell omics. Anal. Bioanal. Chem. https://doi.org/10.1007/s00216-023-04850-0 (2023)Qian, Y., Guo, X. Y., Wang, Y. F., Ouyang, Z. & Ma, X. X. Mobility-modulated sequential dissociation analysis enables structural lipidomics in mass spectrometry imaging. Angew. Chem. Int. Ed. https://doi.org/10.1002/anie.202312275 (2023).Jiang, L. X. et al. Nanospray Desorption Electrospray Ionization (Nano-DESI) mass spectrometry imaging with high ion mobility resolution. J. Am. Soc. Mass Spectrom. 34, 1798–1804 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Soltwisch, J. et al. MALDI-2 on a trapped ion mobility quadrupole time-of-flight instrument for rapid mass spectrometry imaging and ion mobility separation of complex lipid profiles. Anal. Chem. 92, 8697–8703 (2020).Article 
CAS 
PubMed 

Google Scholar 
Garza, K. Y. et al. Desorption electrospray ionization mass spectrometry imaging of proteins directly from biological tissue sections. Anal. Chem. 90, 7785–7789 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Seeley, E. H. & Caprioli, R. M. 3D imaging by mass spectrometry: a new frontier. Anal. Chem. 84, 2105–2110 (2012).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Zhao, C. & Cai, Z. W. Three-dimensional quantitative mass spectrometry imaging in complex system: from subcellular to whole organism. Mass Spectrom. Rev. 41, 469–487 (2022).Article 
CAS 
PubMed 

Google Scholar 
Li, X. P. et al. Nanoscale three-dimensional imaging of drug distributions in single cells via laser desorption post-ionization mass spectrometry. J. Am. Chem. Soc. 143, 21648–21656 (2021).Article 
CAS 
PubMed 

Google Scholar 
Kompauer, M., Heiles, S. & Spengler, B. Atmospheric pressure MALDI mass spectrometry imaging of tissues and cells at 1.4-mu m lateral resolution. Nat. Methods 14, 90–96 (2017).Article 
CAS 
PubMed 

Google Scholar 
Niehaus, M., Soltwisch, J., Belov, M. E. & Dreisewerd, K. Transmission-mode MALDI-2 mass spectrometry imaging of cells and tissues at subcellular resolution. Nat. Methods 16, 925–931 (2019).Article 
CAS 
PubMed 

Google Scholar 
Castro, D. C., Xie, Y. R., Rubakhin, S. S., Romanova, E. V. & Sweedler, J. V. Image-guided MALDI mass spectrometry for high-throughput single-organelle characterization. Nat. Methods 18, 1233–1238 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Rappez, L. et al. SpaceM reveals metabolic states of single cells. Nat. Methods 18, 799–805 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Passarelli, M. K. et al. The 3D OrbiSIMS-label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power. Nat. Methods 14, 1175–1183 (2017).Article 
CAS 
PubMed 

Google Scholar 
Yuan, Z. Y. et al. SEAM is a spatial single nuclear metabolomics method for dissecting tissue microenvironment. Nat. Methods 18, 1223–1232 (2021).Article 
CAS 
PubMed 

Google Scholar 
Wiseman, J. M., Ifa, D. R., Song, Q. Y. & Cooks, R. G. Tissue imaging at atmospheric pressure using desorption electrospray ionization (DESI) mass spectrometry. Angew. Chem. Int. Ed. 45, 7188–7192 (2006).Article 
CAS 

Google Scholar 
Wiseman, J. M. et al. Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues. Proc. Natl Acad. Sci. USA 105, 18120–18125 (2008).Article 
PubMed 
PubMed Central 

Google Scholar 
Li, L. J., Garden, R. W. & Sweedler, J. V. Single-cell MALDI: a new tool for direct peptide profiling. Trends Biotechnol. 18, 151–160 (2000).Article 
CAS 
PubMed 

Google Scholar 
Capolupo, L. et al. Sphingolipids control dermal fibroblast heterogeneity. Science 376, eabh1623, https://doi.org/10.1126/science.abh1623 (2022).Article 
CAS 
PubMed 

Google Scholar 
Moore, J. L. & Charkoftaki, G. A guide to MALDI imaging mass spectrometry for tissues. J. Proteome Res. 22, 3401–3417 (2023).Article 
CAS 
PubMed 

Google Scholar 
Borisov, R. S., Matveeva, M. D. & Zaikin, V. G. Reactive matrices for analytical Matrix-Assisted Laser Desorption/Ionization (MALDI) mass spectrometry. Critic. Rev. Anal. Chem. https://doi.org/10.1080/10408347.2021.2001309 (2021).Zhou, Q. Q., Fulop, A. & Hopf, C. Recent developments of novel matrices and on-tissue chemical derivatization reagents for MALDI-MSI. Anal. Bioanal. Chem. 413, 2599–2617 (2021).Article 
CAS 
PubMed 

Google Scholar 
Qiao, Z. & Lissel, F. MALDI matrices for the analysis of low molecular weight compounds: rational design, challenges and perspectives. Chem. Asian J. 16, 868–878 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Soltwisch, J. et al. Mass spectrometry imaging with laser-induced postionization. Science 348, 211–215 (2015).Article 
CAS 
PubMed 

Google Scholar 
McKinnon, J. C. et al. Enhancing metabolite coverage in MALDI-MSI using laser post-ionisation (MALDI-2). Anal. Methods https://doi.org/10.1039/d3ay01046e (2023).Article 
PubMed 

Google Scholar 
McPhail, D. S. Applications of Secondary Ion Mass Spectrometry (SIMS) in materials science. J. Mater. Sci. 41, 873–903 (2006).Heide, P. V. D. Secondary Ion Mass Spectrometry (John Wiley & Sons, Inc., 2014).Vickerman, J. C. ToF-SIMS: surface analysis by mass spectrometry (SurfaceSpectra, 2001).Huang, D. et al. Secondary ion mass spectrometry: the application in the analysis of atmospheric particulate matter. Anal. Chim. Acta 989, 1–14 (2017).Article 
CAS 
PubMed 

Google Scholar 
Li, K., Liu, J., Grovenor, C. R. M. & Moore, K. L. NanoSIMS imaging and analysis in materials science. Annu. Rev. Anal. Chem. 13, 273–292 (2020).Article 
CAS 

Google Scholar 
Brunet, M. A. & Kraft, M. L. Toward understanding the subcellular distributions of cholesterol and sphingolipids using high-resolution NanoSIMS imaging. Acc. Chem. Res. 56, 752–762 (2023).Article 
CAS 
PubMed 

Google Scholar 
Schaepe, K. et al. Secondary ion mass spectrometry (Elsevier, 2020).Le, M. T. et al. Simultaneous multiplexed imaging of biomolecules in transgenic mouse brain tissues using mass spectrometry imaging: a multi-omic approach. Anal. Chem. 94, 9297–9305 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Tian, H. et al. Successive High-Resolution (H(2)O)(n)-GCIB and C(60)-SIMS imaging integrates multi-omics in different cell types in breast cancer tissue. Anal. Chem. 93, 8143–8151 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Kotowska, A. M. et al. Protein identification by 3D OrbiSIMS to facilitate in situ imaging and depth profiling. Nat. Commun. 11, 5832 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Passarelli, M. K. et al. The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power. Nat. Methods 14, 1175–1183 (2017).Article 
CAS 
PubMed 

Google Scholar 
Pareek, V., Tian, H., Winograd, N. & Benkovic, S. J. Metabolomics and mass spectrometry imaging reveal channeled de novo purine synthesis in cells. Science 368, 283–290 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Keren, L. et al. MIBI-TOF: a multiplexed imaging platform relates cellular phenotypes and tissue structure. Sci. Adv. 5, eaax5851 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Keren, L. et al. A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 174, 1373–1387.e1319 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Angelo, M. et al. Multiplexed ion beam imaging of human breast tumors. Nat. Med. 20, 436–442 (2014).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Moon, D. W. et al. Multiplex protein imaging with secondary ion mass spectrometry using metal oxide nanoparticle-conjugated antibodies. ACS Appl. Mater. Interfaces 12, 18056–18064 (2020).Article 
CAS 
PubMed 

Google Scholar 
Wirtz, T. et al. Towards secondary ion mass spectrometry on the helium ion microscope: an experimental and simulation based feasibility study with He<SUP>+</SUP> and Ne<SUP>+</SUP> bombardment. Appl. Phys. Lett. 101. https://doi.org/10.1063/1.4739240 (2012).Audinot, J. N. et al. Highest resolution chemical imaging based on secondary ion mass spectrometry performed on the helium ion microscope. Rep. Progress Phys. 84. https://doi.org/10.1088/1361-6633/ac1e32 (2021).Sparvero, L. J. et al. Direct mapping of phospholipid ferroptotic death signals in cells and tissues by Gas Cluster Ion Beam Secondary Ion Mass Spectrometry (GCIB-SIMS). Angew. Chem. Int. Ed. 60, 11784–11788 (2021).Article 
CAS 

Google Scholar 
Campbell, D. I., Ferreira, C. R., Eberlin, L. S. & Cooks, R. G. Improved spatial resolution in the imaging of biological tissue using desorption electrospray ionization. Anal. Bioanal. Chem. 404, 389–398 (2012).Article 
CAS 
PubMed 

Google Scholar 
Laskin, J., Heath, B. S., Roach, P. J., Cazares, L. & Semmes, O. J. Tissue imaging using nanospray desorption electrospray ionization mass spectrometry. Anal. Chem. 84, 141–148 (2012).Article 
CAS 
PubMed 

Google Scholar 
Yin, R. C., Burnum-Johnson, K. E., Sun, X. F., Dey, S. K. & Laskin, J. High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry. Nat. Protoc. 14, 3445–3470 (2019).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Yang, M. et al. Nano-DESI mass spectrometry imaging of proteoforms in biological tissues with high spatial resolution. Anal. Chem. 95, 5214–5222 (2023).Article 
CAS 
PubMed 

Google Scholar 
Unsihuay, D. et al. Imaging and analysis of isomeric unsaturated lipids through online photochemical derivatization of carbon-carbon double bonds. Angew. Chem. Int. Ed. 60, 7559–7563 (2021).Article 
CAS 

Google Scholar 
Hale, O. J. & Cooper, H. J. Native mass spectrometry imaging of proteins and protein complexes by Nano-DESI. Anal. Chem. 93, 4619–4627 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Yang, M. X. et al. Proteoform-selective imaging of tissues using mass spectrometry. Angew. Chem. Int. Ed. 61. https://doi.org/10.1002/anie.202200721 (2022).Luo, Z. G. et al. Air flow-assisted ionization imaging mass spectrometry method for easy whole-body molecular imaging under ambient conditions. Anal. Chem. 85, 2977–2982 (2013).Article 
CAS 
PubMed 

Google Scholar 
He, M. J. et al. Comparing DESI-MSI and MALDI-MSI mediated spatial metabolomics and their applications in cancer studies. Front. Oncol. 12. https://doi.org/10.3389/fonc.2022.891018 (2022).Wang, H. A. O. et al. Fast chemical imaging at high spatial resolution by laser ablation inductively coupled plasma mass spectrometry. Anal. Chem. 85, 10107–10116 (2013).Article 
CAS 
PubMed 

Google Scholar 
Kuznetsov, I. et al. Three-dimensional nanoscale molecular imaging by extreme ultraviolet laser ablation mass spectrometry. Nat. Commun. 6. https://doi.org/10.1038/ncomms7944 (2015).Müller, W. H., Verdin, A., De Pauw, E., Malherbe, C. & Eppe, G. Surface-assisted laser desorption/ionization mass spectrometry imaging: a review. Mass Spectrom. Rev. 41, 373–420 (2022).Article 
PubMed 

Google Scholar 
Chen, W. T., Tomalová, I., Preisler, J. & Changa, H. T. Analysis of biomolecules through surface-assisted laser desorption/ionization mass spectrometry employing nanomaterials. J. Chin. Chem. Soc. 58, 769–778 (2011).Article 
CAS 

Google Scholar 
Lu, M. et al. Nanomaterials as assisted matrix of laser desorption/ionization time-of-flight mass spectrometry for the analysis of small molecules. Nanomaterials 7. https://doi.org/10.3390/nano7040087 (2017).Stolee, J. A. & Vertes, A. Toward single-cell analysis by plume collimation in laser ablation electrospray ionization mass spectrometry. Anal. Chem. 85, 3592–3598 (2013).Article 
CAS 
PubMed 

Google Scholar 
Kulkarni, P., Wilschut, R. A., Verhoeven, K. J. F., van der Putten, W. H. & Garbeva, P. LAESI mass spectrometry imaging as a tool to differentiate the root metabolome of native and range-expanding plant species. Planta 248, 1515–1523 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Swales, J. G. et al. Spatial quantitation of drugs in tissues using liquid extraction surface analysis mass spectrometry imaging. Sci. Rep. 6. https://doi.org/10.1038/srep37648 (2016).Kertesz, V. & Van Berkel, G. J. Sampling reliability, spatial resolution, spatial precision, and extraction efficiency in droplet-based liquid microjunction surface sampling. Rapid Commun. Mass Spectrom. 28, 1553–1560 (2014).Article 
CAS 
PubMed 

Google Scholar 
Swales, J. G. et al. Mapping drug distribution in brain tissue using liquid extraction surface analysis mass spectrometry imaging. Anal. Chem. 87, 10146–10152 (2015).Article 
CAS 
PubMed 

Google Scholar 
Giesen, C. et al. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat. Methods 11, 417–422 (2014).Article 
CAS 
PubMed 

Google Scholar 
Jackson, H. W. et al. The single-cell pathology landscape of breast cancer. Nature 578, 615–620 (2020).Article 
CAS 
PubMed 

Google Scholar 
Kuett, L. et al. Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment. Nat. Cancer 3, 122–133 (2022).Article 
CAS 
PubMed 

Google Scholar 
Bandura, D. R. et al. Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal. Chem. 81, 6813–6822 (2009).Article 
CAS 
PubMed 

Google Scholar 
Rendeiro, A. F. et al. The spatial landscape of lung pathology during COVID-19 progression. Nature 593, 564–569 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ptacek, J. et al. Multiplexed ion beam imaging (MIBI) for characterization of the tumor microenvironment across tumor types. Lab. Investig. 100, 1111–1123 (2020).Article 
CAS 
PubMed 

Google Scholar 
Rovira-Clavé, X. et al. Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging. Nature Communications 12. https://doi.org/10.1038/s41467-021-24822-1 (2021).Yagnik, G., Liu, Z. Y., Rothschild, K. J. & Lim, M. J. Highly multiplexed immunohistochemical MALDI-MS imaging of biomarkers in tissues. J. Am. Soc. Mass Spectrom. 32, 977–988 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Thiery, G. et al. Multiplex target protein imaging in tissue sections by mass spectrometry-TAMSIM. Rapid Commun. Mass Spectrom. 21, 823–829 (2007).Article 
CAS 
PubMed 

Google Scholar 
Song, X., Zang, Q., Li, C., Zhou, T. & Zare, R. N. Immuno-desorption electrospray ionization mass spectrometry imaging identifies functional macromolecules by using microdroplet‐cleavable mass tags. Angew. Chem. Int. Ed. 62. https://doi.org/10.1002/anie.202216969 (2023)Thiery, G. et al. Improvements of targeted multiplex mass spectrometry imaging. Proteomics 8, 3725–3734 (2008).Article 
CAS 
PubMed 

Google Scholar 
Lim, M. J. et al. MALDI HiPLEX-IHC: multiomic and multimodal imaging of targeted intact proteins in tissues. Front. Chem. 11, 1182404 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Lemaire, R. et al. Tag-Mass: specific molecular imaging of transcriptome and proteome by mass spectrometry based on photocleavable tag. J. Proteome Res. 6, 2057–2067 (2007).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Olejnik, J. et al. Photocleavable peptide-DNA conjugates: synthesis and applications to DNA analysis using MALDI-MS. Nucleic Acids Res. 27, 4626–4631 (1999).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Bergman, H. M., Lundin, E., Andersson, M. & Lanekoff, I. Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization. Analyst 141, 3686–3695 (2016).Article 
CAS 
PubMed 

Google Scholar 
Zhang, Y., Buchberger, A., Muthuvel, G. & Li, L. Expression and distribution of neuropeptides in the nervous system of the crab Carcinus maenas and their roles in environmental stress. Proteomics 15, 3969–3979 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ryan, D. J., Spraggins, J. M. & Caprioli, R. M. Protein identification strategies in MALDI imaging mass spectrometry: a brief review. Curr. Opin. Chem. Biol. 48, 64–72 (2019).Article 
CAS 
PubMed 

Google Scholar 
Dilillo, M. et al. Mass spectrometry imaging, laser capture microdissection, and LC-MS/MS of the same tissue section. J. Proteome Res. 16, 2993–3001 (2017).Article 
CAS 
PubMed 

Google Scholar 
Randall, E. C., Race, A. M., Cooper, H. J. & Bunch, J. MALDI imaging of liquid extraction surface analysis sampled tissue. Anal. Chem. 88, 8433–8440 (2016).Article 
CAS 
PubMed 

Google Scholar 
Spraggins, J. M. et al. MALDI FTICR IMS of intact proteins: Using mass accuracy to link protein images with proteomics data. J. Am. Soc. Mass Spectrom. 26, 947–985 (2015).Article 

Google Scholar 
Yang, M. et al. Proteoform-selective imaging of tissues using mass spectrometry. Angew. Chem. Int. Ed. 61, e202200721 (2022).Article 
CAS 

Google Scholar 
McGee, J. P. et al. Automated imaging and identification of proteoforms directly from ovarian cancer tissue. Nat. Commun. 14. https://doi.org/10.1038/s41467-023-42208-3 (2023).Zhang, H. et al. Quantification and molecular imaging of fatty acid isomers from complex biological samples by mass spectrometry. Chem. Sci. 12, 8115–8122 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Sun, R., Tang, W., Li, P. & Li, B. Development of an efficient on-tissue epoxidation reaction mediated by urea hydrogen peroxide for MALDI MS/MS imaging of lipid C═C location isomers. Anal. Chem. 95, 16004–16012 (2023).Article 
CAS 
PubMed 

Google Scholar 
Guo, X. et al. Tandem mass spectrometry imaging enables high definition for mapping lipids in tissues. Angew. Chem. Int. Ed. 62. https://doi.org/10.1002/anie.202214804 (2023).Guo, X. et al. MS3 imaging enables the simultaneous analysis of phospholipid C═C and sn-position isomers in tissues. Anal. Chem. 96, 4259–4265 (2024).Article 
CAS 
PubMed 

Google Scholar 
Mavroudakis, L. & Lanekoff, I. Identification and imaging of prostaglandin isomers utilizing MS3 product ions and silver cationization. J. Am. Soc. Mass Spectrom. 34, 2341–2349 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Kernalléguen, A. et al. Synthetic cannabinoid isomers characterization by MALDI-MS3 imaging: application to single scalp hair. Anal. Chim. Acta 1041, 87–93 (2018).Article 
PubMed 

Google Scholar 
Takeo, E. et al. Tandem mass spectrometry imaging reveals distinct accumulation patterns of steroid structural isomers in human adrenal glands. Anal. Chem. 91, 8918–8925 (2019).Article 
CAS 
PubMed 

Google Scholar 
Lamont, L. et al. Quantitative mass spectrometry imaging of drugs and metabolites: a multiplatform comparison. Anal. Bioanal. Chem. 413, 2779–2791 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Weigand, M. R. et al. Lipid isobar and isomer imaging using nanospray desorption electrospray ionization combined with triple quadrupole mass spectrometry. Anal. Chem. https://doi.org/10.1021/acs.analchem.3c04705 (2023).Nizioł, J. et al. Localization of metabolites of human kidney tissue with infrared laser-based selected reaction monitoring mass spectrometry imaging and Silver-109 nanoparticle-based surface assisted laser desorption/ionization mass spectrometry imaging. Anal. Chem. 92, 4251–4258 (2020).Article 
PubMed 
PubMed Central 

Google Scholar 
Lamont, L. et al. Targeted drug and metabolite imaging: desorption electrospray ionization combined with triple quadrupole mass spectrometry. Anal. Chem. 90, 13229–13235 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Li, K. W., Gonzalez-Lozano, M. A., Koopmans, F. & Smit, A. B. Recent developments in Data Independent Acquisition (DIA) mass spectrometry: application of quantitative analysis of the brain proteome. Front. Mol. Neurosci. 13. https://doi.org/10.3389/fnmol.2020.564446 (2020).Ellis, S. R. et al. Automated, parallel mass spectrometry imaging and structural identification of lipids. Nat. Methods 15, 515–518 (2018).Article 
CAS 
PubMed 

Google Scholar 
Morosi, L. et al. MSIpixel: a fully automated pipeline for compound annotation and quantitation in mass spectrometry imaging experiments. Brief. Bioinform. 25. https://doi.org/10.1093/bib/bbad463 (2024).Heuckeroth, S. et al. On-tissue dataset-dependent MALDI-TIMS-MS2 bioimaging. Nat. Commun. 14. https://doi.org/10.1038/s41467-023-43298-9 (2023)Zhao, C. et al. Molecular network strategy in multi-omics and mass spectrometry imaging. Curr. Opin. Chem. Biol. 70. https://doi.org/10.1016/j.cbpa.2022.102199 (2022).Verbeeck, N., Caprioli, R. M. & van de Plas, R. Unsupervised machine learning for exploratory data analysis in imaging mass spectrometry. Mass Spectrom. Rev. 39, 245–291 (2020).Article 
CAS 
PubMed 

Google Scholar 
Robichaud, G., Garrard, K. P., Barry, J. A. & Muddiman, D. C. MSiReader: an open-source interface to view and analyze high resolving power MS imaging files on matlab platform. J. Am. Soc. Mass Spectrom. 24, 718–721 (2013).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Bokhart, M. T., Nazari, M., Garrard, K. P. & Muddiman, D. C. MSiReader v1.0: evolving open-source mass spectrometry imaging software for targeted and untargeted analyses. J. Am. Soc. Mass Spectrom. 29, 8–16 (2018).Article 
CAS 
PubMed 

Google Scholar 
Bemis, K. D. et al. Cardinal: an R package for statistical analysis of mass spectrometry-based imaging experiments. Bioinformatics 31, 2418–2420 (2015).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Bemis, K. D. et al. Probabilistic segmentation of mass spectrometry (MS) images helps select important ions and characterize confidence in the resulting segments. Mol. Cell. Proteom. 15, 1761–1772 (2016).Article 
CAS 

Google Scholar 
Veselkov, K. et al. BASIS: high-performance bioinformatics platform for processing of large-scale mass spectrometry imaging data in chemically augmented histology. Sci. Rep. 8. https://doi.org/10.1038/s41598-018-22499-z (2018).Dong, J. et al. iMS2Net: a multiscale networking methodology to decipher metabolic synergy of organism. iScience 25. https://doi.org/10.1016/j.isci.2022.104896 (2022).Pang, X. et al. Mapping metabolic networks in the brain by ambient mass spectrometry imaging and metabolomics. Anal. Chem. 93, 6746–6754 (2021).Article 
CAS 
PubMed 

Google Scholar 
Zhao, C. et al. Breast cancer proliferation and deterioration-associated metabolic heterogeneity changes induced by exposure of bisphenol S, a widespread replacement of bisphenol A. J. Hazard. Mater. 414. https://doi.org/10.1016/j.jhazmat.2021.125391 (2021).Zhang, H., Ouyang, Z. & Zhang, W. Advances in mass spectrometry for clinical analysis: data acquisition, interpretation and information integration. Trends Anal. Chem. 169. https://doi.org/10.1016/j.trac.2023.117380 (2023).Abdelmoula, W. M. et al. Peak learning of mass spectrometry imaging data using artificial neural networks. Nat. Commun. 12. https://doi.org/10.1038/s41467-021-25744-8 (2021).Ovchinnikova, K., Stuart, L., Rakhlin, A., Nikolenko, S. & Alexandrov, T. ColocML: machine learning quantifies co-localization between mass spectrometry images. Bioinformatics 36, 3215–3224 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Guo, L. et al. Divide and conquer: a flexible deep learning strategy for exploring metabolic heterogeneity from mass spectrometry imaging data. Anal. Chem. https://doi.org/10.1021/acs.analchem.2c04045 (2022).Article 
PubMed 

Google Scholar 
Reynolds, D. A., Quatieri, T. F. & Dunn, R. B. Speaker verification using adapted Gaussian mixture models. Digital Signal Process. A Rev. J. 10, 19–41 (2000).Article 

Google Scholar 
Smets, T., De Keyser, T., Tousseyn, T., Waelkens, E. & De Moor, B. Correspondence-aware manifold learning for microscopic and spatial omics imaging: a novel data fusion method bringing mass spectrometry imaging to a cellular resolution. Anal. Chem. 93, 3452–3460 (2021).Article 
CAS 
PubMed 

Google Scholar 
Race, A. M. et al. Deep learning-based annotation transfer between molecular imaging modalities: an automated workflow for multimodal data integration. Anal. Chem. 93, 3061–3071 (2021).Article 
CAS 
PubMed 

Google Scholar 
Pezzotti, N., Höllt, T., Lelieveldt, B., Eisemann, E. & Vilanova, A. Hierarchical stochastic neighbor embedding. Comput. Graph. Forum 35, 21–30 (2016).Article 

Google Scholar 
Behrmann, J. et al. Deep learning for tumor classification in imaging mass spectrometry. Bioinformatics 34, 1215–1223 (2018).Article 
CAS 
PubMed 

Google Scholar 
Alexandrov, T. Spatial metabolomics and imaging mass spectrometry in the age of artificial intelligence. Annu. Rev. Biomed. Data Sci. 16, 40–40 (2020).
Google Scholar 
Oetjen, J. et al. Benchmark datasets for 3D MALDI- and DESI-imaging mass spectrometry. GigaScience 4. https://doi.org/10.1186/s13742-015-0059-4 (2015).Schramm, T. et al. ImzML – a common data format for the flexible exchange and processing of mass spectrometry imaging data. J. Proteom. 75, 5106–5110 (2012).Article 
CAS 

Google Scholar 
Spengler, B. Mass spectrometry imaging of biomolecular information. Anal. Chem. 87, 64–82 (2015).Article 
CAS 
PubMed 

Google Scholar 
Xu, G. & Li, J. Recent advances in mass spectrometry imaging for multiomics application in neurology. J. Comp. Neurol. 527, 2158–2169 (2019).Article 
PubMed 

Google Scholar 
Cillero-Pastor, B. & Heeren, R. M. Matrix-assisted laser desorption ionization mass spectrometry imaging for peptide and protein analyses: a critical review of on-tissue digestion. J. Proteome Res. 13, 325–335 (2014).Article 
CAS 
PubMed 

Google Scholar 
Andersson, M., Groseclose, M. R., Deutch, A. Y. & Caprioli, R. M. Imaging mass spectrometry of proteins and peptides: 3D volume reconstruction. Nat. Methods 5, 101–108 (2008).Article 
CAS 
PubMed 

Google Scholar 
Groseclose, M. R., Andersson, M., Hardesty, W. M. & Caprioli, R. M. Identification of proteins directly from tissue: in situ tryptic digestions coupled with imaging mass spectrometry. J. Mass Spectrom. 42, 254–262 (2007).Article 
CAS 
PubMed 

Google Scholar 
Heijs, B. et al. Multimodal mass spectrometry imaging of N-Glycans and proteins from the same tissue section. Anal. Chem. 88, 7745–7753 (2016).Article 
CAS 
PubMed 

Google Scholar 
Angel, P. M. et al. Mapping extracellular matrix proteins in formalin-fixed, paraffin-embedded tissues by MALDI imaging mass spectrometry. J. Proteome Res 17, 635–646 (2018).Article 
CAS 
PubMed 

Google Scholar 
Clift, C. L., Drake, R. R., Mehta, A. & Angel, P. M. Multiplexed imaging mass spectrometry of the extracellular matrix using serial enzyme digests from formalin-fixed paraffin-embedded tissue sections. Anal. Bioanal. Chem. 413, 2709–2719 (2021).Article 
CAS 
PubMed 

Google Scholar 
Clift, C. L. et al. Evaluation of therapeutic collagen-based biomaterials in the infarcted mouse heart by extracellular matrix targeted MALDI imaging mass spectrometry. J. Am. Soc. Mass Spectrom. 32, 2746–2754 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Angel, P. M. et al. Zonal regulation of collagen-type proteins and posttranslational modifications in prostatic benign and cancer tissues by imaging mass spectrometry. Prostate 80, 1071–1086 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
DelaCourt, A. T., Liang, H., Drake, R. R., Angel, P. M. & Mehta, A. S. Novel combined enzymatic approach to analyze nonsialylated N-linked Glycans through MALDI imaging mass spectrometry. J. Proteome Res. 21, 1930–1938 (2022).Article 
CAS 
PubMed 

Google Scholar 
Shariatgorji, R. et al. Spatial visualization of comprehensive brain neurotransmitter systems and neuroactive substances by selective in situ chemical derivatization mass spectrometry imaging. Nat. Protoc. 16, 3298–3321 (2021).Article 
CAS 
PubMed 

Google Scholar 
Sun, C. L., Liu, W., Geng, Y. L. & Wang, X. On-tissue derivatization strategy for mass spectrometry imaging of carboxyl-containing metabolites in biological tissues. Anal. Chem. 92, 12126–12131 (2020).Article 
CAS 
PubMed 

Google Scholar 
Wang, L. Z. et al. On-tissue chemical oxidation followed by derivatization for mass spectrometry imaging enables visualization of primary and secondary hydroxyl-containing metabolites in biological tissues. Anal. Chem. 95, 1975–1984 (2023).Article 
CAS 

Google Scholar 
Zhang, H. et al. On-tissue derivatization with Girard’s reagent P Enhances N-Glycan signals for formalin-fixed paraffin-embedded tissue sections in MALDI mass spectrometry imaging. Anal. Chem. 92, 13361–13368 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Zhang, H. et al. On-tissue amidation of sialic acid with aniline for sensitive imaging of sialylated N-glycans from FFPE tissue sections via MALDI mass spectrometry. Anal. Bioanal. Chem. 414, 5263–5274 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Holst, S. et al. Linkage-specific in situ Sialic Acid derivatization for N-Glycan mass spectrometry imaging of formalin-fixed paraffin-embedded tissues. Anal. Chem. 88, 5904–5913 (2016).Article 
CAS 
PubMed 

Google Scholar 
Waldchen, F., Spengler, B. & Heiles, S. Reactive matrix-assisted laser desorption/ionization mass spectrometry imaging using an intrinsically photoreactive paterno-buchi matrix for double-bond localization in isomeric phospholipids. J. Am. Chem. Soc. 141, 11816–11820 (2019).Article 
PubMed 

Google Scholar 
Deng, L. L. et al. Serpentine Ultralong Path with Extended Routing (SUPER) high resolution traveling wave ion Mobility-MS using structures for lossless ion manipulations. Anal. Chem. 89, 4628–4634 (2017).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Giles, K. et al. A cyclic ion mobility-mass spectrometry system. Anal. Chem. 91, 8564–8573 (2019).Article 
CAS 
PubMed 

Google Scholar 
Xie, C. Y. et al. Chiral derivatization-enabled discrimination and on-tissue detection of proteinogenic amino acids by ion mobility mass spectrometry. Chem. Sci. 13, 14114–14123 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Sugiyama, E. et al. Charged chiral derivatization for enantioselective imaging of d-,l-2-hydroxyglutaric acid using ion mobility spectrometry/mass spectrometry. Chem. Commun. 59. https://doi.org/10.1039/d3cc01963b (2023).Balluff, B., Hopf, C., Siegel, T. P., Grabsch, H. I. & Heeren, R. M. A. Batch effects in MALDI mass spectrometry imaging. J. Am. Soc. Mass Spectrom. 32, 628–635 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Vandenbosch, M. et al. Toward omics-scale quantitative mass spectrometry imaging of lipids in brain tissue using a multiclass internal standard mixture. Anal. Chem. https://doi.org/10.1021/acs.analchem.3c02724 (2023).Kertesz, V. & Cahill, J. F. Spatially resolved absolute quantitation in thin tissue by mass spectrometry. Anal. Bioanal. Chem. 413, 2619–2636 (2021).Article 
CAS 
PubMed 

Google Scholar 
Tobias, F. & Hummon, A. B. Considerations for MALDI-based quantitative mass spectrometry imaging studies. J. Proteome Res. 19, 3620–3630 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Stopka, S. A. et al. Chemical quantarray: a quantitative tool for mass spectrometry imaging. Anal. Chem. 95, 11243–11253 (2023).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Nezhad, Z. S., Salazar, J. P., Pryce, R. S., Munter, L. M. & Chaurand, P. Absolute quantification of cholesterol from thin tissue sections by silver-assisted laser desorption ionization mass spectrometry imaging. Anal. Bioanal. Chem. 414, 6947–6954 (2022).Article 
CAS 
PubMed 

Google Scholar 
Baquer, G. et al. What are we imaging? Software tools and experimental strategies for annotation and identification of small molecules in mass spectrometry imaging. Mass Spectrom. Rev. 42, 1927–1964 (2023).Article 
CAS 
PubMed 

Google Scholar 
Denti, V. et al. Spatial multiomics of lipids, N-Glycans, and Tryptic peptides on a single FFPE tissue section. J. Proteome Res. 21, 2798–2809 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Habenstein, J. et al. Transcriptomic, peptidomic, and mass spectrometry imaging analysis of the brain in the ant Cataglyphis nodus. J. Neurochem. 158, 391–412 (2021).Article 
CAS 
PubMed 

Google Scholar 
Liu, Y. et al. Elevation of sulfatides in ovarian cancer: an integrated transcriptomic and lipidomic analysis including tissue-imaging mass spectrometry. Mol. Cancer 9, 186 (2010).Article 
PubMed 
PubMed Central 

Google Scholar 
Flint, L. E. et al. Characterization of an aggregated three-dimensional cell culture model by multimodal mass spectrometry imaging. Anal. Chem. 92, 12538–12547 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ravi, V. M. et al. Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma. Cancer Cell 40, 639–655.e13 (2022).Article 
CAS 
PubMed 

Google Scholar 
Sabine Becker, J. Imaging of metals in biological tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS): state of the art and future developments. J. Mass Spectrom. 48, 255–268 (2013).Article 
CAS 
PubMed 

Google Scholar 
Sikora, K. N. et al. Dual mass spectrometric tissue imaging of nanocarrier distributions and their biochemical effects. Anal. Chem. 92, 2011–2018 (2020).Article 
CAS 
PubMed 

Google Scholar 
Sun, C. L. et al. Spatially resolved multi-omics highlights cell-specific metabolic remodeling and interactions in gastric cancer. Nat. Commun. 14. https://doi.org/10.1038/s41467-023-38360-5 (2023).Vicari, M. et al. Spatial multimodal analysis of transcriptomes and metabolomes in tissues. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01937-y (2023).Tian, H., Rabbani, S. S. N. E., Vickerman, J. C. & Winograd, N. Multiomics imaging using high-energy water gas cluster ion beam secondary ion mass spectrometry [(H2O) n ‑GCIB-SIMS] of frozen-hydrated cells and tissue. Anal. Chem. 93, 7808–7814 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Balluff, B., Heeren, R. M. A. & Race, A. M. An overview of image registration for aligning mass spectrometry imaging with clinically relevant imaging modalities. J. Mass Spectrom. Adv. Clin. Lab. 23, 26–38 (2022).Article 
CAS 
PubMed 

Google Scholar 

Hot Topics

Related Articles