College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
J Vasc Interv Radiol. 2012 Mar;23(3):385-95. doi: 10.1016/j.jvir.2011.11.018. Epub 2012 Jan 20.
To develop a translational rat hepatocellular carcinoma (HCC) disease model for magnetic resonance (MR) imaging and image-guided interventional oncologic investigations.
Male rats underwent sham control surgery (n = 6), selective bile duct ligation (SBDL; n = 4), or common bile duct ligation (CBDL; n = 6), with procedure optimization in four rats and N1S1 hepatoma cell injection into two or three sites in the livers of 12 rats. All rats subsequently underwent MR imaging to assess tumor establishment and volume. Mesenteric angiography and percutaneous MR-guided laser ablation of the liver were performed in a subgroup of animals (n = 4). Animal weight and liver test results were monitored. After harvesting, the livers were subjected to gross and microscopic analysis. Tumor volume and laboratory parameters were assessed between ligation groups.
MR imaging demonstrated hyperintense T2 and hypointense T1 lesions with tumor induction in five of 10 (50.0%), seven of eight (87.5%), and 12 of 12 (100%) sites in the control, SBDL, and CBDL groups, respectively. Tumor volumes differed significantly by group (P < .02). Mesenteric angiography demonstrated an enhancing tumor stain. Clinical and laboratory assessment revealed a significant decrease in weight (P = .01) and albumin level (P < .01) and an increase in total bilirubin level (P = .02) in CBDL rats but not SBDL rats (P = 1.0). Histologic examination showed high-grade HCCs with local and vascular invasion within the context of early fibrosis in CBDL and SBDL rats. MR-guided laser ablation generated a 1-2-cm ablation zone with histologic findings consistent with reversible and irreversible injury.
A biologically relevant rat HCC disease model has been developed for MR imaging and preliminary interventional oncologic applications.
开发用于磁共振(MR)成像和图像引导介入肿瘤学研究的翻译大鼠肝细胞癌(HCC)疾病模型。
雄性大鼠接受假手术对照(n = 6)、选择性胆管结扎(SBDL;n = 4)或胆总管结扎(CBDL;n = 6),4 只大鼠进行了手术优化,12 只大鼠的肝脏内 2 或 3 个部位注射 N1S1 肝癌细胞。所有大鼠随后接受 MR 成像以评估肿瘤建立和体积。对一组动物(n = 4)进行肠系膜血管造影和经皮 MR 引导的肝脏激光消融。监测动物体重和肝功能检查结果。收获后,对肝脏进行大体和显微镜分析。结扎组之间评估肿瘤体积和实验室参数。
MR 成像显示在对照组、SBDL 组和 CBDL 组的 10、8 和 12 个部位中的 5、7 和 12 个部位分别显示 T2 高信号和 T1 低信号的肿瘤诱导病变。肿瘤体积在各组之间差异有统计学意义(P <.02)。肠系膜血管造影显示肿瘤染色增强。临床和实验室评估显示 CBDL 大鼠体重(P =.01)和白蛋白水平(P <.01)显著下降,总胆红素水平(P =.02)升高,但 SBDL 大鼠体重(P = 1.0)和白蛋白水平无变化。组织学检查显示 CBDL 和 SBDL 大鼠存在早期纤维化背景下的高级 HCC,伴有局部和血管侵犯。MR 引导的激光消融产生了 1-2cm 的消融区,组织学发现与可逆和不可逆损伤一致。
已经开发出用于 MR 成像和初步介入肿瘤学应用的具有生物学相关性的大鼠 HCC 疾病模型。