In vivo staging of alcoholic and non-alcoholic liver disease

西方的生活方式，尤其是高热量摄入和过度饮酒，往往会导致糖尿病或酒精性和非酒精性脂肪性肝病，然后是酒精性和非酒精性脂肪性肝炎，这构成了肝细胞癌(HCC)的基础。为了获得尽可能高的存活率，尽管大多数临床干预始于肝癌的检测，但肝癌的早期检测是至关重要的。为了避免脂肪性肝病的晚期发展为肝癌，对脂肪性肝病各个阶段的非侵入性识别和定性作为这一多步骤过程的先兆具有重要的临床意义。要做到这一点，治疗干预必须尽早开始，早在癌症发生之前，并以适当的机制为目标。然而，对于与酒精相关的脂肪肝的晚期治疗方案通常是缺乏的，因为除了“停止饮酒”的方法之外，测试的化合物都没有显著改善治疗结果的效果。饮酒和由此导致的酒精性肝病仍然是肝细胞癌发生的主要组成部分。该项目将利用最先进的医学成像技术，在相关的小鼠模型中具体描述脂肪肝的不同阶段，从轻度脂肪变性到脂肪性肝炎再到肝细胞癌，这些模型与临床情况非常相似。除了形态MRI，定量组织特征(T1、T2松弛时间、组织脂肪含量和脂肪组成)和免疫MRI，再加上葡萄糖和脂肪酸代谢和增殖的PET研究，产生独特的成像指纹，使脂肪肝疾病的空间分辨分期成为可能。

Western lifestyle, especially high caloric intake and excessive consumption of alcohol, often leads to diabetes or alcoholic and non-alcoholic fatty liver disease, followed by alcoholic and non-alcoholic steatohepatitis, which form the basis for hepatocellular carcinoma (HCC). In order to achieve the best possible survival rates, the early detection of liver cancer is of paramount importance, although most clinical intervention begins with the detection of liver cancer. In order to avoid the late stage of fatty liver disease, the development of liver cancer, the non-invasive identification and characterization of the various stages of fatty liver disease as precursors of this multi-step process is of great clinical importance. To do this, the therapeutic interventions must begin as early as possible, well before the onset of a carcinoma, and aim for appropriate mechanisms. However, treatment options for the later stages of alcohol-related fatty liver disease are usually absent, since none of the compounds tested has significantly improved the therapy outcome beyond the "stop drinking" approach. Alcohol consumption and the resulting alcoholic liver disease remain one of the major components of HCC development.The project will specifically characterize the different stages of fatty liver disease, ranging from mild steatosis to steatohepatitis to HCC, in relevant mouse models closely resembling the clinical situation using state-of-the-art medical imaging technologies. Beyond morphological MRI, quantitative tissue characteristics (T1-, T2- relaxation times, tissue fat content and fat composition) and immuno-MRI, coupled with the PET study of glucose and fatty acid metabolism and proliferation, produce a unique imaging fingerprint and enable spatially resolved staging of the fatty liver disease.