Mass spectrometric imaging of lipids using desorption electrospray ionization

Abstract

Desorption electrospray ionization (DESI), a relatively new ambient ionization technique used in mass spectrometry (MS), allows for the direct analysis of samples such as thin tissue sections, to be conducted outside of vacuum in the ambient environment and often without sample preparation. DESI-MS has been used in order to systematically characterize phospholipids, which are abundant species in biological tissue samples. Lipids play important biological roles and differences in lipid compositions have been seen in diseases such as cancer and Alzheimer's disease. Imaging of thin tissue sections exploits the ability of DESI-MS to study these lipids directly in the biological matrix. In imaging MS (IMS), a mass spectrum is recorded at each pixel while moving the surface containing the sample so that the entire sample area is covered. The information in these mass spectra can be combined to create a 2D chemical image of the sample, combining information on spatial distribution with information on chemical identity from the characteristic ions in the mass spectra. DESI-MS has been used to image a variety of tissue samples including human liver adenocarcinoma, rat brain, human breast tissue and canine abdominal tumor tissue. Comparisons between diseased and normal tissue are made in these studies.

Fig. 1

Desorption electrospray ionization (DESI). (a) Schematic of DESI; (b) schematic of tissue imaging analysis using DESI.

Fig. 2

(a) Lipid profile of porcine brain extract in negative mode spraying 1:1 methanol/water. (b) MS/MS of m/z 888 from (a); (1) [M−H–galactose sulfate–C₁₆H₃₀O]⁻; (2) [M−H–H₂O–C₂₂H₄₃CH=C=O]⁻; (3) [M−H–C₁₆H₃₀O]⁻. Adapted from original figure by Manicke et al. [44] with permission from Elsevier, copyright 2008.

Fig. 3

Schematic representation of imaging experiment. Each pixel on the tissue surface results in a unique MS spectrum.

Fig. 4

Positive ion DESI mass spectra for metastatic human liver adenocarcinoma tissue, spraying methanol/water (1:1, v/v) with 0.1% NH₄OH added. (a) Representative DESI mass spectrum from nontumor region of the tissue. (b) Representative DESI mass spectrum from cancerous region of the tissue. Adapted from original figure by Wiseman et al. [46] with permission from Wiley–VHC, copyright 2005.

Fig. 5

Images of selected lipid molecular ions [M−H]⁻ from a rat brain tissue section. (a) Optical image of the coronal section of the rate brain. cc = corpos callosum; CPu = striatum; Cbc = celebral cortex; LV= lateral ventricle; aca = anterior part of anterior commissure. (b–i) Ion images of selected lipid species. Reprinted from Wiseman et al. [31] with permission from Wiley–VCH, copyright 2006.

Fig. 6

Human breast tissue section showing negative ion mass spectrometry images. (A) Distribution of m/z 887 in normal tissue. (B) Distribution of m/z 885 in normal tissue. (C) Distribution of m/z 887 in invasive DC. (D) Distribution of m/z 885 in invasive DC. Unpublished data; false colors show intensity; tissue shown is approx. 6 mm by 4.2 mm by 10 µm.

Fig. 7

Canine abdominal tumor tissue showing (a) optical image of tissue section and (b)–(d) the negative ion mass spectrometry images of the molecules. (b) Molecular ion m/z 826. (c) Molecular ion m/z 795. (d) Molecular ion m/z 738.