title: Inflation-Fixation Method for Lipidomic Mapping of Lung Biopsies by Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging.
abstract: 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.
authors.affiliation: University of Maryland , School of Pharmacy, Department of Pharmaceutical Sciences, 20 North Pine Street, Baltimore, Maryland 21201, United States.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Carter
authors.affiliation: University of Maryland , School of Pharmacy, Department of Pharmaceutical Sciences, 20 North Pine Street, Baltimore, Maryland 21201, United States.
authors.forename: Jace W
authors.initials: JW
authors.lastname: Jones
authors.affiliation: University of Maryland , School of Medicine, Department of Radiation Oncology, 655 West Baltimore Street, Baltimore, Maryland 21201, United States.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Farese
authors.affiliation: University of Maryland , School of Medicine, Department of Radiation Oncology, 655 West Baltimore Street, Baltimore, Maryland 21201, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: MacVittie
authors.affiliation: University of Maryland , School of Pharmacy, Department of Pharmaceutical Sciences, 20 North Pine Street, Baltimore, Maryland 21201, United States.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Kane
mesh_terms: D000818:Animals; D001706:Biopsy; D006652:Histological Techniques; D008055:Lipids / Q000032:analysis*; D008168:Lung / Q000737:chemistry*; D008253:Macaca mulatta; D008297:Male; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D008055:Lipids