Absolute metabolite quantification by in vivo NMR spectroscopy: II. a multicentre trial of protocols for in vivo localised proton studies of human brain |
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| Institution: | 1. United Medical and Dental Schools of Guy’s and St Thomas’ Hospitals, London, UK;2. Università degli Studi di Bologna, Bologna, Italy;3. University of Liverpool, Liverpool, UK;4. University College London, London, UK;5. Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, UK;7. Institute of Radiological Sciences, Dublin, Ireland;11. Ospedale Policlinico, Perugia, Italy;12. Universität Freiburg, Freiburg, Germany;8. Universität zu Köln, Cologne, Germany;9. Institut für Medizinische Physik, Universität Wien, Vienna, Austria;71. Dansk Videncenter for Magnetisk Resonans, Copenhagen, Denmark;112. Università degli Studi di Modena, Modena, Italy;123. Istituto Superiore di Sanità, Rome, Italy;1. Radiology and Image Guided Intervention Service, Instituto do Câncer do Estado de São Paulo, University of São Paulo, São Paulo, Brazil;2. Radiology Department, Hospital Sírio Libanês, São Paulo, Brazil;3. Neurosurgery Department, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil;4. Orthopedics Department, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil;5. Radiology Department, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil;1. NMR Laboratory of SANOFI, C&BD (Chemistry & Biotechnology Development Frankfurt Chemistry), Industriepark Hoechst, Building G849, D-65926 Frankfurt/Main, Germany;2. Bruker BioSpin GmbH, Silberstreifen 4, D-76287 Rheinstetten, Germany;1. Department of Chemistry, University of California, Riverside, Riverside, CA, United States;2. Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States |
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| Abstract: | We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20–35 years) determined using the internal water standard method were (mean ± SD): NAA] = 10.0 ± 3.4 mM (n = 53), tCho] = 1.9 ± 1.0 mM (n = 51), Cr + PCr] = 6.5 ± 3.7 mM (n = 51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy. |
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