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Updated: Aug 11, 2026
Capturing Small Molecule Communication Between Tissues and Cells Using Imaging Mass Spectrometry
Published on: April 3, 2019
MALDI mass spectrometry imaging across spatial scales in toxicology: tissue evidence, cellular heterogeneity, and
Yuang Qin1, Jie Lian2, Honggang Nie3
1School of Investigation, People's Public Security University of China, Beijing, 100038, China.
Abstract:
Toxicological responses are inherently spatially heterogeneous, yet conventional analytical strategies generally rely on homogenized samples and therefore provide limited information on where xenobiotics accumulate, which tissue regions or cellular populations are preferentially affected, and how local molecular perturbations relate to pathology and mechanism. Mass spectrometry imaging (MSI) addresses this limitation by enabling label-free, multiplexed, and spatially resolved detection of xenobiotics, metabolites, lipids, peptides, and proteins directly in biological specimens. In this review, we examine the role of MSI in spatial toxicology, with particular emphasis on matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) as a practical core platform for many current tissue-level and emerging cellular-scale toxicology studies. We first discuss why MSI is analytically well suited for spatial toxicology and compare the major MSI platforms in terms of molecular coverage, spatial resolution, and toxicological applicability. We then summarize representative applications at the tissue level, where MSI has already shown clear value in mapping xenobiotic localization, lesion-associated molecular remodeling, and organ-specific toxicity. Next, we discuss cellular-scale MSI and the transition toward true single-cell analysis, emphasizing that current progress is driven more by workflow development, multimodal integration, and computational advances than by routine toxicological deployment. Finally, using per- and polyfluoroalkyl substances as a focused case study, we illustrate how MSI can connect tissue burden, regional bioaccumulation, and localized biochemical response. Overall, MSI is becoming a key analytical framework for mechanistic spatial toxicology, although broader impact will depend on further advances in standardization, annotation confidence, quantification, and multimodal interpretation.
Insights
Mass spectrometry imaging (MSI) overcomes limitations of traditional toxicology by mapping xenobiotics and molecular changes in tissues. This spatial toxicology approach reveals how chemicals affect specific cells and organs, advancing mechanistic understanding.
Area of Science:
- Spatial toxicology
- Analytical chemistry
- Biomolecular analysis
Background:
- Conventional toxicology relies on homogenized samples, losing spatial information on xenobiotic accumulation and tissue effects.
- Understanding the spatial distribution of xenobiotics and their impact on tissue at a molecular level is crucial for mechanistic toxicology.
Purpose of the Study:
- To review the role and applications of mass spectrometry imaging (MSI) in spatial toxicology.
- To highlight matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) as a core platform for tissue and cellular toxicology.
- To discuss the potential and challenges of MSI for advancing mechanistic toxicology.
Main Methods:
- Review of existing literature on MSI applications in toxicology.
- Comparison of different MSI platforms for molecular coverage, spatial resolution, and toxicological relevance.
- Case study using per- and polyfluoroalkyl substances (PFAS) to illustrate MSI capabilities.
Main Results:
- MSI enables label-free, spatially resolved detection of xenobiotics, metabolites, and proteins in biological tissues.
- Tissue-level MSI applications demonstrate value in mapping xenobiotic localization, molecular remodeling, and organ-specific toxicity.
- Emerging cellular-scale MSI shows promise but requires further workflow and computational development for routine toxicological use.
Conclusions:
- MSI is a powerful tool for mechanistic spatial toxicology, providing insights into chemical exposure and biological response.
- Further advancements in standardization, annotation, quantification, and multimodal integration are needed for broader MSI adoption in toxicology.
- MSI, particularly MALDI-MSI, is pivotal for understanding localized biochemical responses and tissue burden in toxicological studies.
