Open AccessInflation-Fixation Method for Lipidomic Mapping of Lung Biopsies by Matrix Assisted Laser Desorption/Ionization–Mass Spectrometry Imaging
Author(s) -
Claire L. Carter,
Jace W. Jones,
Ann M. Farese,
Thomas J. MacVittie,
Maureen A. Kane
Publication year - 2016
Publication title -
analytical chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.117
H-Index - 332
eISSN - 1520-6882
pISSN - 0003-2700
DOI - 10.1021/acs.analchem.6b00165
Subject(s) - mass spectrometry imaging , chemistry , maldi imaging , mass spectrometry , lung , ion suppression in liquid chromatography–mass spectrometry , analyte , surface enhanced laser desorption/ionization , pathology , matrix assisted laser desorption/ionization , desorption , chromatography , medicine , electrospray ionization , liquid chromatography–mass spectrometry , sample preparation in mass spectrometry , organic chemistry , adsorption
Chronic respiratory diseases are among the leading causes of deaths worldwide and major contributors of morbidity and global disease burden. To appropriately investigate lung disease, the respiratory airways must be fixed in their physiological orientation and should be inflated prior to investigations. We present an inflation-fixation method that enables lipidomic investigations of whole lung samples and resected biopsy specimens by matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). Formalin-inflation enables sample preparation to parallel standard clinical and surgical procedures, in addition to greatly reducing the complexity of analysis, by decreasing the number of analytes in the MALDI plume and reducing adduct formation in the resulting mass spectra. The reduced complexity increased sensitivity and enabled high-resolution imaging acquisitions without any loss in analyte detection at 10 and 20 μm scans. We present a detailed study of over 100 lipid ions detected in positive and negative ion modes covering the conducting and respiratory airways and parts of the peripheral nervous tissue running through the lungs. By defining the resolution required for clear definition of the alveolar space and thus the respiratory airways we have provided a guideline for MSI investigations of respiratory diseases involving the airways, including the interstitium. This study has provided a detailed map of lipid species and their localization within larger mammalian lung samples, for the first time, thus categorizing the lipidome for future MALDI-MSI studies of pulmonary diseases.