DEVELOPMENT, VALIDATION AND APPLICATION OF A METHOD FOR DETERMINATION OF METABOLITE CONCENTRATIONS WITH PRECLINICAL MAGNETIC RESONANCE SPECTROSCOPY

Background: Information on the metabolic content in tissue has diagnostic and prognostic value when examining for example cancer and diseases of the brain. MR spectroscopy is a non-invasive method that allows quantification of metabolite concentrations in vivo, without the use of ionizing radiation, which makes the method highly attractive for both research and clinical applications. However, specialized software is required for generation of so called basis sets, which consist of information on the individual metabolites that are under investigation, and which are required for quantification. Furthermore, method- and MR vendor-specific information must be provided as the basis sets are being generated in order to yield reliable quantification results. A software for generation of basis sets was recently developed at the University of Gothenburg and validated for a preclinical MR system in a previous master thesis project. However, a standardized method for calculation of metabolite concentrations in vivo in the preclinical setting has not yet been developed. Therefore, the purpose of this work was to adapt, validate and apply a method for non-invasive quantification of metabolites from in vivo MR spectroscopy at the preclinical facility at the University of Gothenburg. Method: The software, implemented in MATLAB and previously developed to simulate basis sets for the clinical MR system, was programmatically adapted to import pulse sequence parameters from the preclinical MR system. Validation of the adapted MATLAB software was done by MR spectroscopy measurements on a phantom solution with known concentrations of certain metabolites, followed by metabolite quantification using the LCModel software. Two in vivo experiments were performed to assess the applicability of the method in the preclinical setting: one on the healthy mouse brain and one on a mouse model of human cancer. The point resolved spectroscopy (PRESS) pulse sequence was used for all measurements and simulations.3 Results: The adaption of the software to the preclinical MR system was successful, resulting in simulated basis sets that could be well fitted to the spectra measured in the validation which, in turn, resulted in accurate determination of metabolite concentrations in the phantom. The in vivo experiments resulted in metabolic profiles of the cancer model and the healthy mouse brain that were in agreement with what has been found in previous studies. The method developed in this work will thus enable metabolite quantification of existing and future MR spectroscopy studies at the preclinical MR facility at the University of Gothenburg