In vivo staging of alcoholic and non-alcoholic liver disease

西方的生活方式，特别是高热量摄入和过度饮酒，往往导致糖尿病或酒精性和非酒精性脂肪肝疾病，其次是酒精性和非酒精性脂肪性肝炎，形成肝细胞癌（HCC）的基础。为了达到最佳的生存率，肝癌的早期检测至关重要，尽管大多数临床干预都是从肝癌的检测开始的。为了避免脂肪肝疾病的晚期，肝癌的发展，非侵入性识别和表征脂肪肝疾病的各个阶段作为这个多步骤过程的前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开始，早在癌症发作之前，并针对适当的机制。然而，酒精相关性脂肪肝后期的治疗选择通常是不存在的，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。酒精摄入和由此导致的酒精性肝病仍然是HCC发展的主要组成部分之一。该项目将利用最先进的医学成像技术，在与临床情况非常相似的相关小鼠模型中，具体描述脂肪肝疾病的不同阶段，从轻度脂肪变性到脂肪性肝炎再到HCC。除了形态学MRI，定量组织特征（T1，T2弛豫时间，组织脂肪含量和脂肪成分）和免疫MRI，加上葡萄糖和脂肪酸代谢和增殖的PET研究，产生了独特的成像指纹，并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.