CIBM Center for Biomedical Imaging, Switzerland; Animal Imaging and Technology (AIT), EPFL, Lausanne, Switzerland; Laboratory for Functional and Metabolic Imaging (LIFMET), EPFL, Lausanne, Switzerland.
CIBM Center for Biomedical Imaging, Switzerland; Animal Imaging and Technology (AIT), EPFL, Lausanne, Switzerland.
Anal Biochem. 2022 Jun 15;647:114606. doi: 10.1016/j.ab.2022.114606. Epub 2022 Mar 1.
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 F-FDG PET methodology to compute quantitative 3D maps of the regional cerebral metabolic rate of glucose (CMR) 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 maps were registered to an atlas and the mean CMR from the hippocampus and the cerebellum were associated to the corresponding localized 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.
C 型肝性脑病 (HE) 是一种复杂的神经精神障碍，是慢性肝病的后果。已经有研究表明 C 型 HE 存在能量代谢改变，但关于这方面的体内研究仍然很少，并且报告的结果相互矛盾。在这里，我们提出了一种新的临床前 F-FDG PET 方法，用于从大脑的标记稳态 PET 图像和图像衍生的输入函数计算葡萄糖代谢率 (CMR) 的定量 3D 图谱。当比较具有不同生理学的动物组（如 HE 动物）时，这种定量方法显示出其优势。将 PET CMR 图谱注册到图谱上，并将海马体和小脑的平均 CMR 与相应的局部 H 磁共振波谱采集相关联。这项研究首次提供了 C 型 HE 大鼠模型中脑葡萄糖摄取和神经代谢特征改变的局部和定量信息。在海马体和小脑观察到脑葡萄糖摄取降低 2 倍，同时脑谷氨酰胺增加，主要渗透物减少。这些新发现是深入了解 HE 病理生理学中能量代谢的重要一步。
