PET CMR$_{glc}$ mapping and $^{1}$H MRS show altered glucose uptake and neurometabolic profiles in BDL rats

TL;DR

This study introduces a new PET imaging method to quantitatively map brain glucose metabolism and neurometabolic changes in a rat model of hepatic encephalopathy, revealing significant alterations in glucose uptake and metabolite levels.

Contribution

The paper presents a novel in vivo PET methodology for quantitative 3D mapping of cerebral glucose metabolism in hepatic encephalopathy, linking PET and MR spectroscopy data.

Findings

Brain glucose uptake was halved in HE rats.

Increased brain glutamine levels observed in HE rats.

Decreased osmolytes in hippocampus and cerebellum.

Abstract

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 $\textit{in vivo}$ studies on this matter remain sparse and have reported conflicting results. Here, we propose a novel preclinical $^{18}$F-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 $^{1}$H 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.