title: Visualization of acetaminophen-induced liver injury by time-of-flight secondary ion mass spectrometry.
abstract: Time-of-flight secondary ion mass spectrometry (MS) provides secondary ion images that reflect distributions of substances with sub-micrometer spatial resolution. To evaluate the use of time-of-flight secondary ion MS to capture subcellular chemical changes in a tissue specimen, we visualized cellular damage showing a three-zone distribution in mouse liver tissue injured by acetaminophen overdose. First, we selected two types of ion peaks related to the hepatocyte nucleus and cytoplasm using control mouse liver. Acetaminophen-overdosed mouse liver was then classified into three areas using the time-of-flight secondary ion MS image of the two types of peaks, which roughly corresponded to established histopathological features. The ion peaks related to the cytoplasm decreased as the injury became more severe, and their origin was assumed to be mostly glycogen based on comparison with periodic acid-Schiff staining images and reference compound spectra. This indicated that the time-of-flight secondary ion MS image of the acetaminophen-overdosed mouse liver represented the chemical changes mainly corresponding to glycogen depletion on a subcellular scale. In addition, this technique also provided information on lipid species related to the injury. These results suggest that time-of-flight secondary ion MS has potential utility in histopathological applications.
authors.affiliation: Frontier Research Center, Canon, Ohta-ku, Tokyo 146-8501, Japan. Electronic address: murayama.yohei@canon.co.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Murayama
authors.affiliation: Frontier Research Center, Canon, Ohta-ku, Tokyo 146-8501, Japan.
authors.forename: Shuya
authors.initials: S
authors.lastname: Satoh
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hashiguchi
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Frontier Research Center, Canon, Ohta-ku, Tokyo 146-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000473:pathology*; D003593:Cytoplasm / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods*; D007564:Japan; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008112:Liver Glycogen / Q000032:analysis*; D051379:Mice; D018629:Spectrometry, Mass, Secondary Ion
chemical_list: D018712:Analgesics, Non-Narcotic; D008112:Liver Glycogen; D000082:Acetaminophen
keywords: Acetaminophen; Drug-induced liver injury; Imaging MS; Time-of-flight secondary ion MS; Tissue imaging