Shahryari Mehrgan, Keller Sarah, Meierhofer David, Wallach Iwona, Safraou Yasmine, Guo Jing, Marticorena Garcia Stephan R, Braun Jürgen, Makowski Marcus R, Sack Ingolf, Berndt Nikolaus
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Mass Spectrometry Facility, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Front Bioeng Biotechnol. 2023 Jan 9;10:1042711. doi: 10.3389/fbioe.2022.1042711. eCollection 2022.
The liver is the central metabolic organ. It constantly adapts its metabolic capacity to current physiological requirements. However, the relationship between tissue structure and hepatic function is incompletely understood; this results in a lack of diagnostic markers in medical imaging that can provide information about the liver's metabolic capacity. Therefore, using normal rabbit livers, we combined magnetic resonance elastography (MRE) with proteomics-based kinetic modeling of central liver metabolism to investigate the potential role of MRE for predicting the liver's metabolic function . Nineteen New Zealand white rabbits were investigated by multifrequency MRE and positron emission tomography (PET). This yielded maps of shear wave speed (SWS), penetration rate (PR) and standardized uptake value (SUV). Proteomic analysis was performed after the scans. Hepatic metabolic functions were assessed on the basis of the HEPATOKIN1 model in combination with a model of hepatic lipid-droplet metabolism using liquid chromatography-mass spectrometry. Our results showed marked differences between individual livers in both metabolic functions and stiffness properties, though not in SUV. When livers were divided into 'stiff' and 'soft' subgroups (cutoff SWS = 1.6 m/s), stiff livers showed a lower capacity for triacylglycerol storage, while at the same time showing an increased capacity for gluconeogenesis and cholesterol synthesis. Furthermore, SWS was correlated with gluconeogenesis and PR with urea production and glutamine exchange. In conclusion, our study indicates a close relationship between the viscoelastic properties of the liver and metabolic function. This could be used in future studies to predict non-invasively the functional reserve capacity of the liver in patients.
肝脏是核心代谢器官。它不断根据当前的生理需求调整其代谢能力。然而,组织结构与肝功能之间的关系尚未完全明晰;这导致医学成像中缺乏能够提供肝脏代谢能力信息的诊断标志物。因此,我们以正常兔肝脏为研究对象,将磁共振弹性成像(MRE)与基于蛋白质组学的肝脏核心代谢动力学建模相结合,以探究MRE在预测肝脏代谢功能方面的潜在作用。对19只新西兰白兔进行了多频MRE和正电子发射断层扫描(PET)检查。由此得出了剪切波速度(SWS)、穿透率(PR)和标准化摄取值(SUV)的图谱。扫描后进行了蛋白质组学分析。结合使用液相色谱 - 质谱联用技术的肝脏脂质滴代谢模型,基于HEPATOKIN1模型评估肝脏代谢功能。我们的结果显示,尽管SUV无差异,但个体肝脏在代谢功能和硬度特性方面均存在显著差异。当将肝脏分为“硬”和“软”亚组(SWS临界值 = 1.6 m/s)时,硬肝的三酰甘油储存能力较低,而同时糖异生和胆固醇合成能力增强。此外,SWS与糖异生相关,PR与尿素生成和谷氨酰胺交换相关。总之,我们的研究表明肝脏的粘弹性特性与代谢功能之间存在密切关系。这可用于未来的研究中,以无创地预测患者肝脏的功能储备能力。