title: Fiducial markers for combined 3-dimensional mass spectrometric and optical tissue imaging.
abstract: Mass spectrometric imaging (MSI) has become widely used in the analysis of a variety of biological surfaces. Biological samples are spatially, morphologically, and metabolically complex. Multimodal molecular imaging is an emerging approach that is capable of dealing with this complexity. In a multimodal approach, different imaging modalities can provide precise information about the local molecular composition of the surfaces. Images obtained by MSI can be coregistered with images obtained by other molecular imaging techniques such as microscopic images of fluorescent protein expression or histologically stained sections. In order to properly coregister images from different modalities, each tissue section must contain points of reference, which are visible in all data sets. Here, we report a newly developed coregistration technique using fiducial markers such as cresyl violet, Ponceau S, and bromophenol blue that possess a combination of optical and molecular properties that result in a clear mass spectrometric signature. We describe these fiducial markers and demonstrate an application that allows accurate coregistration and 3-dimensional reconstruction of serial histological and fluorescent microscopic images with MSI images of thin tissue sections from a breast tumor model.
authors.affiliation: FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: Kamila
authors.initials: K
authors.lastname: Chughtai
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.forename: Tiffany R
authors.initials: TR
authors.lastname: Greenwood
authors.forename: Ivo
authors.initials: I
authors.lastname: Klinkert
authors.forename: Erika R
authors.initials: ER
authors.lastname: Amstalden van Hove
authors.forename: Ron M A
authors.initials: RM
authors.lastname: Heeren
authors.forename: Kristine
authors.initials: K
authors.lastname: Glunde
mesh_terms: D000818:Animals; D001391:Azo Compounds; D048588:Benzoxazines; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D001978:Bromphenol Blue; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D013058:Mass Spectrometry; D051379:Mice; D010078:Oxazines; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D001391:Azo Compounds; D048588:Benzoxazines; D014408:Biomarkers, Tumor; D010078:Oxazines; D001978:Bromphenol Blue; C028911:cresyl violet; C032756:ponceau S