Micrometric molecular histology of lipids by mass spectrometry imaging

https://doi.org/10.1016/j.cbpa.2011.04.017Get rights and content

Time-Of-Flight Secondary Ion Mass Spectrometry is compared to other mass spectrometry imaging techniques, and recent improvements of the experimental methods, driven by biological and biomedical applications, are described and discussed. This review shows that this method that can be considered as a micrometric molecular histology is particularly efficient for obtaining images of various lipid species at the surface of a tissue sample, without sample preparation, and with a routine spatial resolution of 1 μm or less.

Highlights

► Comparison of different mass spectrometry imaging methods. ► Cluster time-of-flight secondary ion mass spectrometry. ► Localization of lipids at a resolution of 1 μm or less at the surface of tissues. ► Applications of TOF-SIMS imaging to diseases inducing lipid disorders.

Introduction

Various ex vivo biological imaging methods, such as immunohistochemistry, staining or autoradiography, have been developed to obtain information on the chemical composition at the surface of tissue sections. Among them, mass spectrometry imaging (MSI) is the only one allowing to locate and identify various chemical compounds without selection a priori of a chemical class or compound [1••, 2]. Since this method does not require targeting compounds before the analysis, it makes possible to draw anatomical images of any ion detected in the mass spectra in one single experiment.

Lipids, which can be defined as fat-soluble molecules, have been for a long time considered only as energy storage and as major constituents of the cell membranes. It is now agreed that these classes of compounds are important cell signaling molecules, neurotransmitters and precursors in the regulation of various cellular functions [3]. The importance of lipids in biological sciences is illustrated by the recognition of ‘lipidomics’ as an emerging field among the ‘omics’. The eight lipid categories as defined by the Lipid Maps initiative [4], fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids and polyketides, sterol lipids and prenol lipids (see www.lipidmaps.org), can be analyzed with gas/liquid chromatography coupled to modern mass spectrometers, providing precise identification and quantification. Before their analysis, lipids have to be extracted from the sample, leading to the loss of the spatial information whereas MSI offers a direct sampling over the tissue surface [3, 5].

Section snippets

Comparison with other mass spectrometry imaging methods

Basically, in MSI, a focused beam of photons or energetic ions is used to scan over the surface of a tissue section. The size of this beam defines the size of the pixel that corresponds to each point on which a mass spectrum is recorded. The data acquisition consists in the creation of a volume whose dimensions are x and y, the two geometric dimensions of the sample, and m/z the mass-to-charge ratio of the secondary ions. Any slice of this volume along a given m/z value is an ion density map,

Experimental methods

When indicated, intensity scales of ion images correspond to a dynamic range. Relative quantification of compounds showing similar physical and chemical properties (which means detected and desorbed with the same efficiencies) between two different areas over the same sample surface and scanned under the same experimental conditions is consequently possible. The mass spectra and the peak areas extracted from the different histological regions of the sample, usually called Regions of Interest

Applications

Localization of lipids in organs of model animals proved useful for studying diseases involving lipid disorders. TOF-SIMS was also applied for imaging lipids in plant samples and, apart from lipids, for investigating the distribution of xenobiotic compounds in tissues. All the studies listed below illustrate the TOF-SIMS imaging capabilities, with spatial resolutions of 1 μm or less. Localization of lipids has been studied in the aortic wall [43] and in rat cerebellum [44]. The accumulation of

Conclusion and future prospects

TOF-SIMS bio-imaging mainly suffers from the absence of a true tandem mass analyzer, although a recent development has been made in this direction [51]. It appears that it is with the current state-of-the-art very difficult to obtain molecular mass spectrometric images well below 1 μm [52]. An increase of sensitivity could also help to make this analysis method more popular. This could be obtained with the recent advent of massive cluster ion sources which can not only increase the yields of

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

This work was supported by the Agence Nationale de la Recherche (grants ANR-09-PIRI-0012-04 MASDA-EYE and ANR-2010-BLAN-0805-01 MASS-IMAGE).

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