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Anal Chem. 2018 Nov 6;90(21):12404-12413. doi: 10.1021/acs.analchem.8b02885. Epub 2018 Oct 16.

Next Generation Histology-Directed Imaging Mass Spectrometry Driven by Autofluorescence Microscopy.

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Center for Infectious Disease Research , formerly Seattle Biomedical Research Institute, Seattle , Washington 98109 , United States.
Department of Global Health , University of Washington , Seattle , Washington 98195 , United States.
Delft Center for Systems and Control (DCSC) , Delft University of Technology , 2628 CD , Delft , The Netherlands.


Histology-directed imaging mass spectrometry (IMS) is a spatially targeted IMS acquisition method informed by expert annotation that provides rapid molecular characterization of select tissue structures. The expert annotations are usually determined on digital whole slide images of histological stains where the staining preparation is incompatible with optimal IMS preparation, necessitating serial sections: one for annotation, one for IMS. Registration is then used to align staining annotations onto the IMS tissue section. Herein, we report a next-generation histology-directed platform implementing IMS-compatible autofluorescence (AF) microscopy taken prior to any staining or IMS. The platform enables two histology-directed workflows, one that improves the registration process between two separate tissue sections using automated, computational monomodal AF-to-AF microscopy image registration, and a registration-free approach that utilizes AF directly to identify ROIs and acquire IMS on the same section. The registration approach is fully automated and delivers state of the art accuracy in histology-directed workflows for transfer of annotations (∼3-10 μm based on 4 organs from 2 species) while the direct AF approach is registration-free, allowing targeting of the finest structures visible by AF microscopy. We demonstrate the platform in biologically relevant case studies of liver stage malaria and human kidney disease with spatially targeted acquisition of sparsely distributed (composing less than one tenth of 1% of the tissue section area) malaria infected mouse hepatocytes and glomeruli in the human kidney case study.

[Available on 2019-11-06]
[Indexed for MEDLINE]

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