title: Mass spectrometry imaging for in situ kinetic histochemistry.
abstract: Tissues are composed of diverse cell subpopulations each with distinct metabolic characteristics that influence overall behavior. Unfortunately, traditional histopathology imaging techniques are 'blind' to the spatially ordered metabolic dynamics within tissue. While mass spectrometry imaging enables spatial mapping of molecular composition, resulting images are only a static snapshot in time of molecules involved in highly dynamic processes; kinetic information of flux through metabolic pathways is lacking. To address this limitation, we developed kinetic mass spectrometry imaging (kMSI), a novel technique integrating soft desorption/ionization mass spectrometry with clinically accepted in vivo metabolic labeling of tissue with deuterium to generate images of kinetic information of biological processes. Applied to a tumor, kMSI revealed heterogeneous spatial distributions of newly synthesized versus pre-existing lipids, with altered lipid synthesis patterns distinguishing region-specific intratumor subpopulations. Images also enabled identification and correlation of metabolic activity of specific lipids found in tumor regions of varying grade.
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Louie
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Bowen
authors.forename: Stephanie
authors.initials: S
authors.lastname: McAlhany
authors.forename: Yurong
authors.initials: Y
authors.lastname: Huang
authors.forename: John C
authors.initials: JC
authors.lastname: Price
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Mao
authors.forename: Marc
authors.initials: M
authors.lastname: Hellerstein
authors.forename: Trent R
authors.initials: TR
authors.lastname: Northen
mesh_terms: D045744:Cell Line, Tumor; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D008055:Lipids / Q000032:analysis*; D013058:Mass Spectrometry / Q000295:instrumentation*; D057054:Molecular Imaging / Q000295:instrumentation*; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*
chemical_list: D008055:Lipids