title: A multimodal imaging workflow to visualize metal mixtures in the human placenta and explore colocalization with biological response markers.
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 or through our laboratory's website, .
authors.affiliation: Exposure Biology, Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1057, New York City, New York NY 10029, USA. manish.arora@mssm.edu.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Niedzwiecki
authors.forename: Christine
authors.initials: C
authors.lastname: Austin
authors.forename: Romain
authors.initials: R
authors.lastname: Remark
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Estrada-Gutierrez
authors.forename: Aurora
authors.initials: A
authors.lastname: Espejel-Nuñez
authors.forename: Hector
authors.initials: H
authors.lastname: Borboa-Olivares
authors.forename: Mario
authors.initials: M
authors.lastname: Guzman-Huerta
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Wright
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.forename: Manish
authors.initials: M
authors.lastname: Arora
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology; D013058:Mass Spectrometry; D008670:Metals / Q000378:metabolism*; D064847:Multimodal Imaging / Q000379:methods*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D015415:Biomarkers; D008670:Metals