Molecular imaging by mass spectrometry — looking beyond classical histology

Schwamborn, Kristina; Caprioli, Richard M.

doi:10.1038/nrc2917

Cited by 314 publications

(247 citation statements)

References 68 publications

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“…Well established techniques for MSI of biological tissue include SIMS [2], desorption electrospray ionization (DESI) [3], matrix assisted laser desorption/ionization (MALDI) [4,5], and laser desorption/ionization (LDI) among others. These techniques capture lipid species in the low molecular weight range, which have been shown to be closely associated with histologic or histopathologic tissue types [6][7][8][9][10]. Thus, MSI has the potential to provide fully automated, MSbased tissue identification systems for next generation chemical histology.…”

Section: Introductionmentioning

confidence: 99%

XMS: Cross-Platform Normalization Method for Multimodal Mass Spectrometric Tissue Profiling

Golf

Muirhead

Speller

et al. 2014

J. Am. Soc. Mass Spectrom.

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Abstract. Here we present a proof of concept cross-platform normalization approach to convert raw mass spectra acquired by distinct desorption ionization methods and/ or instrumental setups to cross-platform normalized analyte profiles. The initial step of the workflow is database driven peak annotation followed by summarization of peak intensities of different ions from the same molecule. The resulting compoundintensity spectra are adjusted to a method-independent intensity scale by using predetermined, compound-specific normalization factors. The method is based on the assumption that distinct MS-based platforms capture a similar set of chemical species in a biological sample, though these species may exhibit platform-specific molecular ion intensity distribution patterns. The method was validated on two sample sets of (1) porcine tissue analyzed by laser desorption ionization (LDI), desorption electrospray ionization (DESI), and rapid evaporative ionization mass spectrometric (REIMS) in combination with Fourier transformationbased mass spectrometry; and (2) healthy/cancerous colorectal tissue analyzed by DESI and REIMS with the latter being combined with time-of-flight mass spectrometry. We demonstrate the capacity of our method to reduce MS-platform specific variation resulting in (1) high inter-platform concordance coefficients of analyte intensities; (2) clear principal component based clustering of analyte profiles according to histological tissue types, irrespective of the used desorption ionization technique or mass spectrometer; and (3) accurate "blind" classification of histologic tissue types using cross-platform normalized analyte profiles.

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Section: Introductionmentioning

confidence: 99%

XMS: Cross-Platform Normalization Method for Multimodal Mass Spectrometric Tissue Profiling

Golf

Muirhead

Speller

et al. 2014

J. Am. Soc. Mass Spectrom.

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“…[1][2][3][4] Using MSI hundreds of analytes may be imaged at a single time, rather than single-substrate techniques requiring the development of additional fluorophores for traditional confocal microscopy, or staining for histology. [5][6][7] Additionally, MSI can be used in either a targeted or a discovery-based fashion, making it an attractive approach to look at the overlap between the distribution of chemical species. Presented within are methods for the growth, preparation, and matrix assisted laser desorption ionization/desorption (MALDI) imaging of small samples (~1 mm in diameter) of three-dimensional multicellular cell cultures.…”

Section: Introductionmentioning

confidence: 99%

Sample Preparation Strategies for Mass Spectrometry Imaging of 3D Cell Culture Models

Wheatcraft

Liu

Hummon

2014

JoVE

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Three dimensional cell cultures are attractive models for biological research. They combine the flexibility and cost-effectiveness of cell culture with some of the spatial and molecular complexity of tissue. For example, many cell lines form 3D structures given appropriate in vitro conditions. Colon cancer cell lines form 3D cell culture spheroids, in vitro mimics of avascular tumor nodules. While immunohistochemistry and other classical imaging methods are popular for monitoring the distribution of specific analytes, mass spectrometric imaging examines the distribution of classes of molecules in an unbiased fashion. While MALDI mass spectrometric imaging was originally developed to interrogate samples obtained from humans or animal models, this report describes the analysis of in vitro three dimensional cell cultures, including improvements in sample preparation strategies. Herein is described methods for growth, harvesting, sectioning, washing, and analysis of 3D cell cultures via matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) imaging. Using colon carcinoma 3D cell cultures as a model system, this protocol demonstrates the ability to monitor analytes in an unbiased fashion across the 3D cell culture system with MALDI-MSI.

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“…MALDI IMS is particularly superior in providing accurate spatial distribution of singly charged proteins from biological sections. [26][27][28] However, effective measurements of the MALDI IMS are greatly dependent on the quality of sample preparations, e.g. the uniformity of matrix deposition or the requirement of specialized substrates.…”

mentioning

confidence: 99%

“…[23][24][25][26] MALDI is currently the most widely used ionization sources for IMS. MALDI IMS is particularly superior in providing accurate spatial distribution of singly charged proteins from biological sections.…”

mentioning

confidence: 99%

Top-Down Atmospheric Ionization Mass Spectrometry Microscopy Combined With Proteogenomics

Hsu

Baker²,

Gaasterland³

et al. 2017

Anal. Chem.

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Mass spectrometry-based protein analysis has become an important methodology for proteogenomic mapping by providing evidence for the existence of proteins predicted at the genomic level. However, screening and identification of proteins directly on tissue samples, where histological information is preserved, remain challenging. Here we demonstrate that the ambient ionization source, nanospray desorption electrospray ionization (nanoDESI), interfaced with light microscopy allows for protein profiling directly on animal tissues at the microscopic scale. Peptide fragments for mass spectrometry analysis were obtained directly on ganglia of the medicinal leech (Hirudo medicinalis) without in-gel digestion. We found that a hypothetical protein, which is predicted by the leech genome, is highly expressed on the specialized neural cells that are uniquely found in adult sex segmental ganglia. Via this top-down analysis, a posttranslational modification (PTM) of tyrosine sulfation to this neuropeptide was resolved. This three-in-one platform, including mass spectrometry, microscopy, and genome mining, provides an effective way for mappings of proteomes under the lens of a light microscope.

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Molecular imaging by mass spectrometry — looking beyond classical histology

Cited by 314 publications

References 68 publications

XMS: Cross-Platform Normalization Method for Multimodal Mass Spectrometric Tissue Profiling

XMS: Cross-Platform Normalization Method for Multimodal Mass Spectrometric Tissue Profiling

Sample Preparation Strategies for Mass Spectrometry Imaging of 3D Cell Culture Models

Top-Down Atmospheric Ionization Mass Spectrometry Microscopy Combined With Proteogenomics

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