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Desorption Electrospray Ionization (DESI) Mass Spectrometric Imaging of Spatially Regulated In Vivo Metabolic Rates

by Charlotte Reininger Lewis

Institution: Brigham Young University
Year: 2017
Keywords: DESI; mass spectrometry; tissue imaging; Alzheimer's disease; Chemistry
Posted: 02/01/2018
Record ID: 2151245
Full text PDF: https://scholarsarchive.byu.edu/etd/6555


Abstract

Desorption electrospray ionization (DESI) is an ambient ionization technique used for mass spectrometric imaging of biological samples. When coupled with isotopic ratio measurements of deuterium-labeled tissues, DESI provides a means of measuring metabolic rates on a spatially resolved basis. In vivo metabolic rates are desired to better understand diseases such as Alzheimer's, Parkinson's, Huntington's, and various forms of cancer that negatively impact metabolic rates within different organs of the human body. Although DESI has been used to image lipids and metabolites of a variety of tissues and other imaging techniques, such as NIMS, have been used to study kinetic turnover rates, DESI has not yet been used to study in vivo metabolic rates using deuterium labeled tissue. This thesis describes how we optimized our DESI source for imaging of biological tissue, how we developed a MATLAB graphical user interface (GUI) to process and interpret the large mass spectral data files, how we conducted our initial mouse brain study for proof-of-concept, and how we plan to implement our DESI imaging in a study with mouse models of Alzheimer's disease. Our initial mouse brain study involved labeling mice with deuterium enriched water, preparing tissue slices for DESI analysis, imaging the tissue slices using DESI coupled with a Bruker mass spectrometer, analyzing the mass spectral data using our custom-designed image_inspector program, confirming identification of lipids using MS/MS, and creating incorporation curves to measure in vivo metabolic rates.

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