Spatially Resolved Metabolomics: From Metabolite Mapping to Function Visualising

Overview

Journal Clin Transl Med

Publisher Wiley

Specialty General Medicine

Date 2024 Oct 26

PMID 39456123

Authors

Xinyue Min

Yiran Zhao

Meng Yu

Wenchao Zhang

Xinyi Jiang

Kaijing Guo

Xiangyi Wang

Jianpeng Huang

Tong Li

Lixin Sun

Jiuming He

Affiliations

Soon will be listed here.

Abstract

Mass spectrometry imaging (MSI)-based spatially resolved metabolomics addresses the limitations inherent in traditional liquid chromatography-tandem mass spectrometry (LC-MS)-based metabolomics, particularly the loss of spatial context within heterogeneous tissues. MSI not only enhances our understanding of disease aetiology but also aids in the identification of biomarkers and the assessment of drug toxicity and therapeutic efficacy by converting invisible metabolites and biological networks into visually rendered image data. In this comprehensive review, we illuminate the key advancements in MSI-driven spatially resolved metabolomics over the past few years. We first outline recent innovations in preprocessing methodologies and MSI instrumentation that improve the sensitivity and comprehensiveness of metabolite detection. We then delve into the progress made in functional visualization techniques, which enhance the precision of metabolite identification and annotation. Ultimately, we discuss the significant potential applications of spatially resolved metabolomics technology in translational medicine and drug development, offering new perspectives for future research and clinical translation. HIGHLIGHTS: MSI-driven spatial metabolomics preserves metabolite spatial information, enhancing disease analysis and biomarker discovery. Advances in MSI technology improve detection sensitivity and accuracy, expanding bioanalytical applications. Enhanced visualization techniques refine metabolite identification and spatial distribution analysis. Integration of MSI with AI promises to advance precision medicine and accelerate drug development.

References

Vijayalakshmi K, Shankar V, Bain R, Nolley R, Sonn G, Kao C . Identification of diagnostic metabolic signatures in clear cell renal cell carcinoma using mass spectrometry imaging. Int J Cancer. 2019; 147(1):256-265. PMC: 8571954. DOI: 10.1002/ijc.32843. View

Bakker B, Vaes R, Aberle M, Welbers T, Hankemeier T, Rensen S . Preparing ductal epithelial organoids for high-spatial-resolution molecular profiling using mass spectrometry imaging. Nat Protoc. 2022; 17(4):962-979. DOI: 10.1038/s41596-021-00661-8. View

Molina-Millan L, Korber A, Flinders B, Cillero-Pastor B, Cuypers E, Heeren R . MALDI-2 Mass Spectrometry for Synthetic Polymer Analysis. Macromolecules. 2023; 56(19):7729-7736. PMC: 10569092. DOI: 10.1021/acs.macromol.3c01401. View

Baquer G, Semente L, Rafols P, Martin-Saiz L, Bookmeyer C, Fernandez J . rMSIfragment: improving MALDI-MSI lipidomics through automated in-source fragment annotation. J Cheminform. 2023; 15(1):80. PMC: 10504721. DOI: 10.1186/s13321-023-00756-2. View

He J, Sun C, Li T, Luo Z, Huang L, Song X . Erratum: A Sensitive and Wide Coverage Ambient Mass Spectrometry Imaging Method for Functional Metabolites Based Molecular Histology. Adv Sci (Weinh). 2019; 6(1):1802201. PMC: 6325592. DOI: 10.1002/advs.201802201. View

Xie Y, Castro D, Rubakhin S, Trinklein T, Sweedler J, Lam F . Multiscale biochemical mapping of the brain through deep-learning-enhanced high-throughput mass spectrometry. Nat Methods. 2024; 21(3):521-530. PMC: 10927565. DOI: 10.1038/s41592-024-02171-3. View

Yang C, Wu R, Liu H, Qin L, Chen L, Xu H . Polyacrylamide gel as a new embedding medium for the enhancement of metabolite MALDI imaging. Chem Commun (Camb). 2023; 59(26):3842-3845. DOI: 10.1039/d2cc07075h. View

Eisenstein M . Seven technologies to watch in 2022. Nature. 2022; 601(7894):658-661. DOI: 10.1038/d41586-022-00163-x. View

Mittal P, Condina M, Klingler-Hoffmann M, Kaur G, Oehler M, Sieber O . Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging. Cancers (Basel). 2021; 13(21). PMC: 8582378. DOI: 10.3390/cancers13215388. View

10.

Samal J, Palomino T, Chen J, Muddiman D, Segura T . Enhanced Detection of Charged -Glycans in the Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometric Imaging. Anal Chem. 2023; 95(29):10913-10920. PMC: 10640919. DOI: 10.1021/acs.analchem.3c00494. View

11.

Shi Y, Hu H, Hao Q, Wu R, Wang L, Qin L . Michler's ethylketone as a novel negative-ion matrix for the enhancement of lipid MALDI tissue imaging. Chem Commun (Camb). 2021; 58(5):633-636. DOI: 10.1039/d1cc05718a. View

12.

Chen Y, Hu D, Zhao L, Tang W, Li B . Unraveling metabolic alterations in transgenic mouse model of Alzheimer's disease using MALDI MS imaging with 4-aminocinnoline-3-carboxamide matrix. Anal Chim Acta. 2022; 1192:339337. DOI: 10.1016/j.aca.2021.339337. View

13.

Handler A, Pedersen G, Troensegaard Nielsen K, Janfelt C, Pedersen A, Clench M . Quantitative MALDI mass spectrometry imaging for exploring cutaneous drug delivery of tofacitinib in human skin. Eur J Pharm Biopharm. 2020; 159:1-10. DOI: 10.1016/j.ejpb.2020.12.008. View

14.

Duivenvoorden A, Claes B, van der Vloet L, Lubbers T, Glunde K, Olde Damink S . Lipidomic Phenotyping Of Human Small Intestinal Organoids Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging. Anal Chem. 2023; 95(50):18443-18450. PMC: 10733903. DOI: 10.1021/acs.analchem.3c03543. View

15.

He J, Tang F, Luo Z, Chen Y, Xu J, Zhang R . Air flow assisted ionization for remote sampling of ambient mass spectrometry and its application. Rapid Commun Mass Spectrom. 2011; 25(7):843-50. DOI: 10.1002/rcm.4920. View

16.

Stutts W, Knuth M, Ekelof M, Mahapatra D, Kullman S, Muddiman D . Methods for Cryosectioning and Mass Spectrometry Imaging of Whole-Body Zebrafish. J Am Soc Mass Spectrom. 2020; 31(4):768-772. PMC: 9375048. DOI: 10.1021/jasms.9b00097. View

17.

Sjovall P, Gregoire S, Wargniez W, Skedung L, Luengo G . 3D Molecular Imaging of Stratum Corneum by Mass Spectrometry Suggests Distinct Distribution of Cholesteryl Esters Compared to Other Skin Lipids. Int J Mol Sci. 2022; 23(22). PMC: 9694581. DOI: 10.3390/ijms232213799. View

18.

Jin B, Pang X, Zang Q, Ga M, Xu J, Luo Z . Spatiotemporally resolved metabolomics and isotope tracing reveal CNS drug targets. Acta Pharm Sin B. 2023; 13(4):1699-1710. PMC: 10149982. DOI: 10.1016/j.apsb.2022.11.011. View

19.

Li Q, Bai J, Ma Y, Sun Y, Zhou W, Wang Z . Pharmacometabolomics and mass spectrometry imaging approach to reveal the neurochemical mechanisms of . J Pharm Anal. 2024; 14(7):100973. PMC: 11340588. DOI: 10.1016/j.jpha.2024.100973. View

20.

Heijs B, Potthoff A, Soltwisch J, Dreisewerd K . MALDI-2 for the Enhanced Analysis of -Linked Glycans by Mass Spectrometry Imaging. Anal Chem. 2020; 92(20):13904-13911. PMC: 7581013. DOI: 10.1021/acs.analchem.0c02732. View