Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Lab Invest. 2013 Jun;93(6):733-43. doi: 10.1038/labinvest.2013.52. Epub 2013 Apr 15.
The cholangiopathies are a diverse group of biliary tract disorders, many of which lack effective treatment. Murine models are an important tool for studying their pathogenesis, but existing noninvasive methods for assessing biliary disease in vivo are not optimal. Here we report our experience with using micro-computed tomography (microCT) and nuclear magnetic resonance (MR) imaging to develop a technique for live-mouse cholangiography. Using mdr2 knockout (mdr2KO, a model for primary sclerosing cholangitis (PSC)), bile duct-ligated (BDL), and normal mice, we performed in vivo: (1) microCT on a Siemens Inveon PET/CT scanner and (2) MR on a Bruker Avance 16.4 T spectrometer, using Turbo Rapid Acquisition with Relaxation Enhancement, IntraGate Fast Low Angle Shot, and Half-Fourier Acquisition Single-shot Turbo Spin Echo methods. Anesthesia was with 1.5-2.5% isoflurane. Scans were performed with and without contrast agents (iodipamide meglumine (microCT), gadoxetate disodium (MR)). Dissection and liver histology were performed for validation. With microCT, only the gallbladder and extrahepatic bile ducts were visualized despite attempts to optimize timing, route, and dose of contrast. With MR, the gallbladder, extra-, and intrahepatic bile ducts were well-visualized in mdr2KO mice; the cholangiographic appearance was similar to that of PSC (eg, multifocal strictures) and could be improved with contrast administration. In BDL mice, MR revealed cholangiographically distinct progressive dilation of the biliary tree without ductal irregularity. In normal mice, MR allowed visualization of the gallbladder and extrahepatic ducts, but only marginal visualization of the diminutive intrahepatic ducts. One mouse died during microCT and MR imaging, respectively. Both microCT and MR scans could be obtained in ≤20 min. We, therefore, demonstrate that MR cholangiography can be a useful tool for longitudinal studies of the biliary tree in live mice, whereas microCT yields suboptimal duct visualization despite requiring contrast administration. These findings support further development and application of MR cholangiography to the study of mouse models of PSC and other cholangiopathies.
胆管疾病是一组多样化的胆道疾病，其中许多疾病缺乏有效治疗方法。 鼠模型是研究其发病机制的重要工具，但现有的非侵入性体内胆道疾病评估方法并不理想。 在这里，我们报告了使用微计算机断层扫描（microCT）和磁共振（MR）成像来开发活体小鼠胆管造影术的经验。 使用多药耐药基因 2 敲除（mdr2KO，原发性硬化性胆管炎（PSC）的模型）、胆管结扎（BDL）和正常小鼠，我们进行了体内：（1）在 Siemens Inveon PET/CT 扫描仪上进行 microCT，（2）在 Bruker Avance 16.4T 光谱仪上进行 MR，使用 Turbo Rapid Acquisition with Relaxation Enhancement、IntraGate Fast Low Angle Shot 和 Half-Fourier Acquisition Single-shot Turbo Spin Echo 方法。 麻醉剂为 1.5-2.5%异氟烷。 扫描在有和没有对比剂（碘普罗胺葡甲胺（microCT），钆塞酸二钠（MR））的情况下进行。 为了验证，进行了解剖和肝组织学检查。 尽管尝试了优化时间、途径和对比剂剂量，但仅使用 microCT 仅可观察到胆囊和肝外胆管。 使用 MR，在 mdr2KO 小鼠中，胆囊、肝内外胆管均得到很好的观察；胆管造影表现类似于 PSC（例如，多灶性狭窄），并可以通过对比剂给药得到改善。 在 BDL 小鼠中，MR 显示胆管树的进行性扩张，胆管无异常。 在正常小鼠中，MR 可以观察到胆囊和肝外胆管，但对微小的肝内胆管的观察仅为边缘性。 一只小鼠在 microCT 和 MR 成像期间死亡。 这两种 microCT 和 MR 扫描均可在≤20 分钟内获得。 因此，我们证明了 MR 胆管造影术可以成为活体小鼠胆管进行纵向研究的有用工具，而 microCT 尽管需要对比剂给药，但胆管可视化效果不佳。 这些发现支持进一步开发和应用 MR 胆管造影术来研究 PSC 和其他胆管疾病的小鼠模型。
