Orsini Vanessa, Zurbruegg Stefan, Pikiolek Monika, Tchorz Jan S, Beckmann Nicolau
Developmental and Molecular Pathways Department, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Neurosciences Department, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Acad Radiol. 2016 Nov;23(11):1446-1453. doi: 10.1016/j.acra.2016.07.008. Epub 2016 Aug 29.
The study aimed to validate magnetic resonance imaging (MRI)-based liver volumetry as a quantitative measure of hepatic regeneration in mice subjected to partial hepatectomy, in view of routine in vivo pharmacologic studies characterizing compounds aiming to accelerate liver regeneration.
Partial hepatectomy was performed in male B6 mice (n = 47). Images were acquired in 14.5 minutes from anesthetized and spontaneously respiring animals, without any gating and without administration of contrast material. Some of the mice (n = 6) were treated with 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene (TCPOBOP), a synthetic agonist of mouse constitutive androstane receptor, or with the corresponding vehicle (n = 6). Postmortem analyses included total liver weight and histologic Ki67 expression.
A highly significant correlation (R = 0.98, P = 1.5 × 10) was obtained between the MRI-derived liver volumes and the postmortem liver weights in hepatectomized, untreated mice. MRI reliably monitored enhanced murine liver regrowth following treatment with TCPOBOP, as confirmed by comparative hepatocyte proliferation (Ki67 expression) and liver weight analysis (R = 0.96, P = 2 × 10).
MRI-based monitoring of liver regrowth in mice without the requirement of euthanizing animals at several time points has been established. In comparison to terminal procedures, the number of hepatectomized mice needed to derive a liver (re)growth curve was reduced by a factor of 6. The feasibility of using this imaging approach in pharmacologic studies in the context of liver regeneration has been demonstrated.
鉴于在体内进行常规药理学研究以表征旨在加速肝脏再生的化合物，本研究旨在验证基于磁共振成像（MRI）的肝脏体积测量作为部分肝切除小鼠肝脏再生的定量指标。
对雄性B6小鼠（n = 47）进行部分肝切除术。在14.5分钟内从麻醉且自主呼吸的动物身上采集图像，无需任何门控且不注射造影剂。部分小鼠（n = 6）用1,4 - 双[2 - （3,5 - 二氯吡啶氧基）]苯（TCPOBOP，小鼠组成型雄甾烷受体的合成激动剂）或相应的赋形剂（n = 6）进行处理。死后分析包括肝脏总重量和组织学Ki67表达。
在未处理的肝切除小鼠中，MRI测量的肝脏体积与死后肝脏重量之间存在高度显著的相关性（R = 0.98，P = 1.5×10）。MRI可靠地监测到用TCPOBOP处理后小鼠肝脏再生增强，这通过比较肝细胞增殖（Ki67表达）和肝脏重量分析得到证实（R = 0.96，P = 2×10）。
已建立基于MRI监测小鼠肝脏再生的方法，无需在多个时间点对动物实施安乐死。与终末程序相比，得出肝脏（再）生长曲线所需的肝切除小鼠数量减少了6倍。已证明在肝脏再生背景下的药理学研究中使用这种成像方法的可行性。
