PET CMR_glc mapping and ¹H-MRS show altered glucose uptake and neurometabolic profiles in BDL rats

Type C hepatic encephalopathy (HE) is a complex neuropsychiatric disorder occurring as a consequence of chronic liver disease. Alterations in energy metabolism have been suggested in type C HE, but in vivo studies on this matter remain sparse and have reported conflicting results. Here, we propose a novel preclinical ¹⁸F-FDG PET methodology to compute quantitative 3D maps of the regional cerebral metabolic rate of glucose (CMR_glc) from a labelling steady-state PET image of the brain and an image-derived input function. This quantitative approach shows its strength when comparing groups of animals with divergent physiology, such as HE animals. PET CMR_glc maps were registered to an atlas and the mean CMR_glc from the hippocampus and the cerebellum were associated to the corresponding localized ¹H MR spectroscopy acquisitions. This study provides for the first time local and quantitative information on both brain glucose uptake and neurometabolic profile alterations in a rat model of type C HE. A 2-fold lower brain glucose uptake, concomitant with an increase in brain glutamine and a decrease in the main osmolytes, was observed in the hippocampus and in the cerebellum. These novel findings are an important step towards new insights into energy metabolism in the pathophysiology of HE.