Mass Spectrometric Imaging of Lipids in Brain Tissue

Abstract

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 Au₃⁺ ions as primary ions. 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 results demonstrate a highly complementary localization of cholesterol and phosphatidylcholine over dimensions from millimeter to micrometer range. Characteristic spatial distributions of several other lipids, including sulfatides and phosphatidylinositols, were observed. Principal component analysis was used to localize regions of the sample surface that show common spectral features. Spectra from different such regions showed large variations in lipid ion signals, indicating large variations in the lipid composition in different regions.