title: 3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma.
abstract: Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder, in which affected individuals develop tumors of the nervous system. Children with NF1 are particularly prone to brain tumors (gliomas) involving the optic pathway that can result in impaired vision. Since tumor formation and expansion requires a cooperative tumor microenvironment, it is important to identify the cellular and acellular components associated with glioma development and growth. In this study, we used 3-D matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) to measure the distributions of multiple molecular species throughout optic nerve tissue in mice with and without glioma, and to explore their spatial relationships within the 3-D volume of the optic nerve and chiasm. 3-D IMS studies often involve extensive workflows due to the high volume of sections required to generate high quality 3-D images. Herein, we present a workflow for 3-D data acquisition and volume reconstruction using mouse optic nerve tissue. The resulting 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions.
  
  
  
  The current work addresses a number of challenges in 3-D MALDI IMS, driven by the small size of the mouse optic nerve and the need to maintain consistency across multiple 2-D IMS experiments. The 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions, which could then be targeted for identification and related back to the biology observed in gliomas of the optic nerve.
authors.affiliation: Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: David M G
authors.initials: DM
authors.lastname: Anderson
authors.affiliation: Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, United States; Delft Center for Systems and Control, Delft University of Technology, Delft, The Netherlands.
authors.forename: Raf
authors.initials: R
authors.lastname: Van de Plas
authors.affiliation: Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Rose
authors.affiliation: Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Salisha
authors.initials: S
authors.lastname: Hill
authors.affiliation: Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Schey
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Solga
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
authors.affiliation: Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, United States. Electronic address: r.caprioli@vanderbilt.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Caprioli
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000737:chemistry / Q000209:etiology / Q000378:metabolism*; D026261:Diazepam Binding Inhibitor / Q000032:analysis / Q000378:metabolism*; D057918:Fiducial Markers; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D057054:Molecular Imaging / Q000379:methods*; D004676:Myelin Basic Protein / Q000032:analysis / Q000378:metabolism*; D009456:Neurofibromatosis 1 / Q000150:complications / Q000378:metabolism*; D009897:Optic Chiasm / Q000737:chemistry / Q000378:metabolism; D020339:Optic Nerve Glioma / Q000737:chemistry / Q000209:etiology / Q000378:metabolism*; D019574:Optic Nerve Neoplasms / Q000737:chemistry / Q000209:etiology / Q000378:metabolism*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D026261:Diazepam Binding Inhibitor; D004676:Myelin Basic Protein
keywords: 3-D imaging; Bottom-up proteomics; Imaging mass spectrometry; MALDI; Optic glioma; Top-down proteomics