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The results demonstrate a highly complementary localization of cholesterol and phosphatidylcholine over dimensions from millimeter to micrometer range

Mass spectrometric imaging of lipids in brain tissue.

ANALYTICAL CHEMISTRY, no. 15 (2004): 4271-4278

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摘要

The spatial distributions of various specific lipids in freeze-dried mouse brain sections were monitored using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Mouse brain sections were prepared by cryosectioning, rinsing in 0.15 M NH3HCOO, and freeze-drying, after which the samples were analyzed directly by TOF-SIMS, using Au-3...更多

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简介
  • Positive and negative TOF-SIMS spectra of the tissue surface contained peaks from quasimolecular ions of a variety of specific lipids, including cholesterol, sulfatides, phosphatidylinositols, and phosphatidylcholines.
  • Images showing the spatial signal intensity distributions of specific ions were recorded across analysis areas ranging from 100 × 100 μm2 to 9 × 9 mm2.
重点内容
  • The development of a new generation of cluster ion sources, notably Au3+ and C60+, has recently been shown to improve the analytical situation significantly when used as primary ion sources in TOF-SIMS; the secondary ion yield of large organic molecules is increased by several orders of magnitude, as compared to when conventional primary ion sources (Ga+, Ar+, etc.) are used
  • In this work, imaging TOF-SIMS is used to analyze the spatial distribution of several specific lipids on the surface of mouse brain sections
  • The high-mass region (>600 u) contains a multitude of peaks that can be assigned to quasimolecular ions of specific lipids
  • The assignments were based on (i) comparison with published electrospray ionization mass spectra,22-27 (ii) comparison with TOF-SIMS spectra recorded on reference samples containing the pure lipid substances, and (iii) calculation of the exact masses and isotope distributions of the different substances
  • (iii) High-quality ion images, showing the spatial distributions of specific lipids on the sample surface, were obtained at a maximum lateral resolution of ∼1 μm, covering analysis areas ranging from 100 × 100 μm2 to 9 × 9 mm2
结果
  • The advantages of using a Au cluster primary ion source in the TOF-SIMS analysis of phospholipids and peptides have recently been demonstrated.13 Images showing the lateral distributions of cholesterol and phospholipids in mouse
  • In this work, imaging TOF-SIMS is used to analyze the spatial distribution of several specific lipids on the surface of mouse brain sections.
  • The cholesterol, phosphatidylinositol (PI), and sulfatide (ST) images correspond to quasimolecular ion peaks and, represent the distributions of specific lipids on the sample surface.
  • The spectrum from the phosphocholine-rich region is, in contrast, dominated by peaks corresponding to three different phosphatidylcholines, while the spectrum from the intermediate area shows similar signal intensities from cholesterol and phosphatidylcholine.
  • The results presented in this work demonstrate the capability of TOF-SIMS to provide spatial information about specific lipids and other organic substances in biological samples.
  • (i) Detailed information about the spatial distributions of specific lipids in freeze-dried tissue sections can be obtained at submicrometer resolutions using TOF-SIMS with Au3+ ions as primary ions.
  • (iii) High-quality ion images, showing the spatial distributions of specific lipids on the sample surface, were obtained at a maximum lateral resolution of ∼1 μm, covering analysis areas ranging from 100 × 100 μm2 to 9 × 9 mm2.
结论
  • (iv) TOF-SIMS spectra from white and gray matter regions, respectively, showed large differences in the relative peak intensities from different lipids.
  • Spectra from white matter regions were dominated by cholesterol-related peaks, while the spectra from gray matter regions showed strong signals from other lipids, including sulfatides, phosphatidylinositols, and phosphatidylcholines.
总结
  • Positive and negative TOF-SIMS spectra of the tissue surface contained peaks from quasimolecular ions of a variety of specific lipids, including cholesterol, sulfatides, phosphatidylinositols, and phosphatidylcholines.
  • Images showing the spatial signal intensity distributions of specific ions were recorded across analysis areas ranging from 100 × 100 μm2 to 9 × 9 mm2.
  • The advantages of using a Au cluster primary ion source in the TOF-SIMS analysis of phospholipids and peptides have recently been demonstrated.13 Images showing the lateral distributions of cholesterol and phospholipids in mouse
  • In this work, imaging TOF-SIMS is used to analyze the spatial distribution of several specific lipids on the surface of mouse brain sections.
  • The cholesterol, phosphatidylinositol (PI), and sulfatide (ST) images correspond to quasimolecular ion peaks and, represent the distributions of specific lipids on the sample surface.
  • The spectrum from the phosphocholine-rich region is, in contrast, dominated by peaks corresponding to three different phosphatidylcholines, while the spectrum from the intermediate area shows similar signal intensities from cholesterol and phosphatidylcholine.
  • The results presented in this work demonstrate the capability of TOF-SIMS to provide spatial information about specific lipids and other organic substances in biological samples.
  • (i) Detailed information about the spatial distributions of specific lipids in freeze-dried tissue sections can be obtained at submicrometer resolutions using TOF-SIMS with Au3+ ions as primary ions.
  • (iii) High-quality ion images, showing the spatial distributions of specific lipids on the sample surface, were obtained at a maximum lateral resolution of ∼1 μm, covering analysis areas ranging from 100 × 100 μm2 to 9 × 9 mm2.
  • (iv) TOF-SIMS spectra from white and gray matter regions, respectively, showed large differences in the relative peak intensities from different lipids.
  • Spectra from white matter regions were dominated by cholesterol-related peaks, while the spectra from gray matter regions showed strong signals from other lipids, including sulfatides, phosphatidylinositols, and phosphatidylcholines.
表格
  • Table1: Peak Assignments in Negative and Positive TOF-SIMS Spectra of Mouse Brain Section peak mass (u)
Download tables as Excel
基金
  • Financial support from the Swedish Government, Ministry of Industry (P.S. and J.L.), and AFA (B.J.) is gratefully acknowledged. Received for review April 23, 2004
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