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Open Access Publications from the University of California

Mass spectrometry imaging for in situ kinetic histochemistry

  • Author(s): Louie, KB
  • Bowen, BP
  • McAlhany, S
  • Huang, Y
  • Price, JC
  • Mao, JH
  • Hellerstein, M
  • Northen, TR
  • et al.

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Tissues are composed of diverse cell subpopulations each with distinct metabolic characteristics that influence overall behavior. Unfortunately, traditional histopathology imaging techniques are â€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.

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