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We therefore explored high\u2010 and ultra\u2010high\u2010field magnetic resonance spectroscopy (<jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content>) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content> and liver biopsy were performed in 30 <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> patients with <jats:styled-content style=\"fixed-case\">NAFL<\/jats:styled-content> (n=8) or <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> (n=22). Hepatic lipid content and composition were measured using 3\u2010Tesla proton (<jats:sup>1<\/jats:sup>H)\u2010<jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content>. 7\u2010Tesla phosphorus (<jats:sup>31<\/jats:sup>P)\u2010<jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content> was applied to determine phosphomonoester (<jats:styled-content style=\"fixed-case\">PME<\/jats:styled-content>) including phosphoethanolamine (<jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content>), phosphodiester (<jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>) including glycerophosphocholine (<jats:styled-content style=\"fixed-case\">GPC<\/jats:styled-content>), phosphocreatine (<jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>r), nicotinamide adenine dinucleotide phosphate (<jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content>), inorganic phosphate (Pi), \u03b3\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> and total phosphorus (<jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>). Saturation transfer technique was used to quantify hepatic <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> flux.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hepatic steatosis in <jats:sup>1<\/jats:sup>H\u2010<jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content> highly correlated with histology (<jats:italic>P<\/jats:italic>&lt;.001) showing higher values in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> than <jats:styled-content style=\"fixed-case\">NAFL<\/jats:styled-content> (<jats:italic>P<\/jats:italic>&lt;.001) without differences in saturated or unsaturated fatty acid indices. <jats:styled-content style=\"fixed-case\">PE<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content> ratio increased with advanced fibrosis (F3\/4) (<jats:italic>P<\/jats:italic>=.002) whereas <jats:styled-content style=\"fixed-case\">GPC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PME<\/jats:styled-content>+<jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content> decreased (<jats:italic>P<\/jats:italic>=.05) compared to no\/mild fibrosis (F0\u20102). \u03b3\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content> was lower in advanced fibrosis (<jats:italic>P<\/jats:italic>=.049), while <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>r\/<jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content> increased (<jats:italic>P<\/jats:italic>=.01). <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content> increased with higher grades of ballooning (<jats:italic>P<\/jats:italic>=.02). Pi\u2010to\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> exchange rate constant (<jats:italic>P<\/jats:italic>=.003) and <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> flux (<jats:italic>P<\/jats:italic>=.001) were lower in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> than <jats:styled-content style=\"fixed-case\">NAFL<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ultra\u2010high\u2010field <jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content>, especially saturation transfer technique uncovers changes in energy metabolism including dynamic <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> flux in inflammation and fibrosis in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>. Non\u2010invasive profiling by <jats:styled-content style=\"fixed-case\">MRS<\/jats:styled-content> appears feasible and may assist further mechanistic and therapeutic studies in <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13451","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T11:12:53Z","timestamp":1493032373000},"page":"1544-1553","source":"Crossref","is-referenced-by-count":43,"title":["Ultra\u2010high\u2010field magnetic resonance spectroscopy in non\u2010alcoholic fatty liver disease: Novel mechanistic and diagnostic insights of energy metabolism in non\u2010alcoholic steatohepatitis and advanced 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