Fiducial Markers for Combined 3-Dimensional Mass Spectrometric and Optical Tissue Imaging

• Published in: Analytical chemistry (Washington) 2012-02, Vol.84 (4), p.1817-1823
• Main Authors: Chughtai, Kamila, Jiang, Lu, Greenwood, Tiffany R, Klinkert, Ivo, Amstalden van Hove, Erika R, Heeren, Ron M. A, Glunde, Kristine
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Animals; Azo Compounds; Benzoxazines; Biological and medical sciences; Biomarkers, Tumor - analysis; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Bromphenol Blue; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chemistry; Exact sciences and technology; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Humans; Image Interpretation, Computer-Assisted; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Mass Spectrometry; Mice; Molecular and cellular biology; Molecular structure; Morphology; Oxazines; Proteins; Spectrometric and optical methods; Tomography, X-Ray Computed; Transplantation, Heterologous; Tumor Cells, Cultured
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/ac203373h

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.