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Issue 4, 2016
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A multimodal imaging workflow to visualize metal mixtures in the human placenta and explore colocalization with biological response markers

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Abstract

Fetal exposure to essential and toxic metals can influence life-long health trajectories. The placenta regulates chemical transmission from maternal circulation to the fetus and itself exhibits a complex response to environmental stressors. The placenta can thus be a useful matrix to monitor metal exposures and stress responses in utero, but strategies to explore the biologic effects of metal mixtures in this organ are not well-developed. In this proof-of-concept study, we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to measure the distributions of multiple metals in placental tissue from a low-birth-weight pregnancy, and we developed an approach to identify the components of metal mixtures that colocalized with biological response markers. Our novel workflow, which includes custom-developed software tools and algorithms for spatial outlier identification and background subtraction in multidimensional elemental image stacks, enables rapid image processing and seamless integration of data from elemental imaging and immunohistochemistry. Using quantitative spatial statistics, we identified distinct patterns of metal accumulation at sites of inflammation. Broadly, our multiplexed approach can be used to explore the mechanisms mediating complex metal exposures and biologic responses within placentae and other tissue types. Our LA-ICP-MS image processing workflow can be accessed through our interactive R Shiny application 'shinyImaging', which is available at https://mniedz.shinyapps.io/shinyImaging/ or through our laboratory's website, http://labs.icahn.mssm.edu/lautenberglab/research-areas/.

Graphical abstract: A multimodal imaging workflow to visualize metal mixtures in the human placenta and explore colocalization with biological response markers

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Publication details

The article was received on 14 Jan 2016, accepted on 07 Mar 2016 and first published on 10 Mar 2016


Article type: Paper
DOI: 10.1039/C6MT00010J
Author version available: Download Author version (PDF)
Citation: Metallomics, 2016,8, 444-452
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    A multimodal imaging workflow to visualize metal mixtures in the human placenta and explore colocalization with biological response markers

    M. M. Niedzwiecki, C. Austin, R. Remark, M. Merad, S. Gnjatic, G. Estrada-Gutierrez, A. Espejel-Nuñez, H. Borboa-Olivares, M. Guzman-Huerta, R. J. Wright, R. O. Wright and M. Arora, Metallomics, 2016, 8, 444
    DOI: 10.1039/C6MT00010J

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