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Currently, MSI is limited to providing a static and ex\u2005vivo snapshot of highly dynamic systems in which molecules are constantly synthesized and consumed. Herein, we demonstrate an innovative MSI methodology to study dynamic molecular changes of amino acids within biological tissues by measuring the dilution and conversion of stable isotopes in a mouse model. We evaluate the method specifically on hepatocellular metabolism of the essential amino acid <jats:sc>l<\/jats:sc>\u2010phenylalanine, associated with liver diseases. Crucially, the method reveals the localized dynamics of <jats:sc>l<\/jats:sc>\u2010phenylalanine metabolism, including its in\u2005vivo hydroxylation to <jats:sc>l<\/jats:sc>\u2010tyrosine and co\u2010localization with other liver metabolites in a time course of samples from different animals. This method thus enables the dynamics of localized biochemical synthesis to be studied directly from biological tissues.<\/jats:p>","DOI":"10.1002\/anie.201702669","type":"journal-article","created":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T18:04:47Z","timestamp":1494525887000},"page":"7146-7150","source":"Crossref","is-referenced-by-count":43,"title":["Detection of Localized Hepatocellular Amino Acid Kinetics by using Mass Spectrometry Imaging of Stable Isotopes"],"prefix":"10.1002","volume":"56","author":[{"given":"Martijn","family":"Arts","sequence":"first","affiliation":[{"name":"Department of General Surgery (NUTRIM) Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zita","family":"Soons","sequence":"additional","affiliation":[{"name":"Department of General Surgery (NUTRIM) Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane R.","family":"Ellis","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Imaging Institute (M4I) Division of Imaging Mass Spectrometry Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keely A.","family":"Pierzchalski","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Imaging Institute (M4I) Division of Imaging Mass Spectrometry Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Balluff","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Imaging Institute (M4I) Division of Imaging Mass Spectrometry Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert B.","family":"Eijkel","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Imaging Institute (M4I) Division of Imaging Mass Spectrometry Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig J.","family":"Dubois","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology (MAASTRO, GROW) Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasja G.","family":"Lieuwes","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology (MAASTRO, GROW) Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stijn M.","family":"Agten","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (CARIM) Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman M.","family":"Hackeng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (CARIM) Maastricht University  Postbus 616 6200 MD Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J. 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