Insights from the downfield proton MR spectrum: establishing peak assignments and novel pathophysiologic findings in hepatic encephalopathy

Motivation: A comprehensive picture of cerebral energy metabolism alterations in hepatic encephalopathy (HE) is still missing and 1H-MRS studies were so far limited to the upfield region. Goal(s): Use metabolite-cycling (MC) to investigate 1H-MRS downfield resonances, in particular glutamine and energy metabolites, in a rat model of HE. Approach: Acquisitions with MC in the short-TE full-intensity SPECIAL sequence at 14.1T in striatum of 10 HE and 10 control rats. Results: Glucose (5.23ppm) was reliably measured and severely depleted in HE, while ATP (isolated 6.1ppm resonance) remained unchanged. The strong correlation between glutamine upfield and downfield resonances confirms the identification of downfield glutamine peaks (6.8/7.5ppm). Impact: Metabolite-cycled 1H-MRS used here in an animal model of hepatic encephalopathy enabled unique access to energy metabolites with downfield resonances (glucose, ATP) and will shed new light on energy metabolism alterations at stake in this disease.