動態電腦斷層影像於土撥鼠肝癌動物模式之應用

Abstract

肝癌是全世界最常見的癌症之一，特別是在亞洲地區有較高的發生率。其中，慢性肝炎病毒感染是導致肝癌最重要的病因。為了進行肝癌的基礎及轉譯研究，我們需要合適的動物模式。土撥鼠（eastern woodchuck, Marmota monax）是目前最為貼近由慢性B型肝炎引發肝癌的動物模式。牠可以被一種和人類B型肝炎病毒（hepatitis B virus, HBV）非常相似的土撥鼠肝炎病毒（woodchuck hepatitis virus, WHV）感染而形成慢性肝炎，而在感染後的一到四年後會發展成肝癌。 在人類肝癌的診斷及追蹤方面，動態電腦斷層檢查（dynamic computed tomography）是最重要的影像檢查工具。肝癌具有非常典型的影像學表現：在動脈相（arterial phase）有良好的顯影，且在靜脈相（venous phase）的顯影則比周圍肝臟組織低。除此之外，電腦斷層檢查和超音波相比，其優點是較為客觀，且沒有死角。因此，我們希望發展出土撥鼠的動態電腦斷層造影技術，以做為此動物模式的影像學檢查工具，進而應用於人類肝癌之研究。 我們針對20隻感染慢性肝炎的土撥鼠進行超音波及動態電腦斷層檢查，並且於四個月後及一年後進行追蹤。我們分析了腫瘤之電腦斷層影像表現，並且和超音波以及屍體解剖的結果做一對照。在總共18顆腫瘤之中，有83.3%呈現和人類肝癌一樣的典型影像學表現，並且有相似的腫瘤中央壞死情形。和人類肝癌影像學表現較不同的是，土撥鼠沒有肝硬化的情形，也沒有發現大血管的侵犯。電腦斷層檢查對於診斷土撥鼠的肝癌有很好的敏感性（90.9%）和特異性（100%），未來將可以應用於更多關於土撥鼠肝癌的研究。

Hepatocellular carcinoma (HCC) is a common cancer worldwide, with especially higher incidence in Asia. Chronic hepatitis B virus (HBV) infection is one of the major causes of HCC. For the basic and translational researches for HCC, an appropriate animal model is needed. Eastern woodchuck (Marmota monax) is a useful animal model which is similar to the HBV- related HCC in humans. Woodchuck can be infected with woodchuck hepatitis virus (WHV), a virus with high similarity to human HBV, and develops chronic hepatitis. After infection, woodchuck HCC develops within one to four years. Dynamic computed tomography (CT) is an important imaging technique for diagnosing and follow up human HCC. HCC has typical image appearances on dynamic CT, showing well-enhancement in arterial phase and washout (less enhancement than liver parenchyma) in venous phase. In addition, image acquisition in CT is less operator dependent than in ultrasonography, and is not limited by echo windows. Therefore, we would like to develop dynamic CT techniques as an imaging tool in woodchuck hepatoma model, and could be applied in researches in human HCC. We performed ultrasonography and dynamic CT in 20 woodchucks with chronic WHV infection. Follow up CT scan was performed after 4 months and 1 year. We analyzed the image appearances in dynamic CT scans, and correlated with findings in sonography and autopsy. Total 18 tumors were identified, and 83.3% of them showed typical image appearances similar to human HCCs. No evidence of liver cirrhosis or major vascular invasion was identified. The sensitivity (90.9%) and specificity (100%) of dynamic CT for diagnosing woodchuck HCC, and could be applied in future researches in this animal model.