From the Institute for Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany (F.B., T.L., S.K., V.S., W.L., F.K.); Department for Diagnostic and Interventional Radiology, RWTH Aachen University, Aachen, Germany (T.L.); Institute of Pathology, RWTH Aachen University, Aachen, Germany (B.K., S.S., P.B.); and Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany (S.R.T.).
Invest Radiol. 2024 Oct 1;59(10):699-710. doi: 10.1097/RLI.0000000000001075. Epub 2024 Apr 10.
Chronic liver diseases (CLDs) have diverse etiologies. To better classify CLDs, we explored the ability of longitudinal multiparametric MRI (magnetic resonance imaging) in depicting alterations in liver morphology, inflammation, and hepatocyte and macrophage activity in murine high-fat diet (HFD)- and carbon tetrachloride (CCl 4 )-induced CLD models.
Mice were either untreated, fed an HFD for 24 weeks, or injected with CCl 4 for 8 weeks. Longitudinal multiparametric MRI was performed every 4 weeks using a 7 T MRI scanner, including T1/T2 relaxometry, morphological T1/T2-weighted imaging, and fat-selective imaging. Diffusion-weighted imaging was applied to assess fibrotic remodeling and T1-weighted and T2*-weighted dynamic contrast-enhanced MRI and dynamic susceptibility contrast MRI using gadoxetic acid and ferucarbotran to target hepatocytes and the mononuclear phagocyte system, respectively. Imaging data were associated with histopathological and serological analyses. Principal component analysis and clustering were used to reveal underlying disease patterns.
The MRI parameters significantly correlated with histologically confirmed steatosis, fibrosis, and liver damage, with varying importance. No single MRI parameter exclusively correlated with 1 pathophysiological feature, underscoring the necessity for using parameter patterns. Clustering revealed early-stage, model-specific patterns. Although the HFD model exhibited pronounced liver fat content and fibrosis, the CCl 4 model indicated reduced liver fat content and impaired hepatocyte and macrophage function. In both models, MRI biomarkers of inflammation were elevated.
Multiparametric MRI patterns can be assigned to pathophysiological processes and used for murine CLD classification and progression tracking. These MRI biomarker patterns can directly be explored clinically to improve early CLD detection and differentiation and to refine treatments.
慢性肝脏疾病（CLD）有多种病因。为了更好地对 CLD 进行分类，我们探索了纵向多参数磁共振成像（MRI）在描述高脂肪饮食（HFD）和四氯化碳（CCl 4 ）诱导的 CLD 模型中肝形态、炎症以及肝细胞和巨噬细胞活性改变的能力。
未处理组、HFD 喂养 24 周组和 CCl 4 注射 8 周组的小鼠分别进行纵向多参数 MRI 检查，使用 7 T MRI 扫描仪进行 T1/T2 弛豫度、形态 T1/T2 加权成像和脂肪选择性成像。扩散加权成像用于评估纤维重塑，T1 加权和 T2*-加权动态对比增强 MRI 以及使用钆塞酸和 Ferucarbotran 靶向肝细胞和单核吞噬细胞系统的动态对比 MRI。将影像学数据与组织病理学和血清学分析相关联。使用主成分分析和聚类来揭示潜在的疾病模式。
MRI 参数与经组织学证实的脂肪变性、纤维化和肝损伤具有显著相关性，重要性各不相同。没有单一的 MRI 参数与单一的病理生理特征完全相关，这强调了使用参数模式的必要性。聚类揭示了早期、模型特异性的模式。尽管 HFD 模型表现出明显的肝脏脂肪含量和纤维化，但 CCl 4 模型表明肝脏脂肪含量降低且肝细胞和巨噬细胞功能受损。在这两种模型中，MRI 炎症生物标志物均升高。
多参数 MRI 模式可归因于病理生理过程，并用于对小鼠 CLD 进行分类和进展跟踪。这些 MRI 生物标志物模式可以直接在临床上探索，以提高早期 CLD 的检测和鉴别，并改善治疗方法。
