不可切除性肝脏泡球蚴病治疗前后活性特征变化规律的MRI评价研究

Hepatic alveolar echinococcosis (HAE) is caused by the parasitic cestode Echinococcus multilocularis. More than 70% cases are inoperable at the time of diagnosis because of the tumor-like growth of the parasite with diffuse infiltration of non-resectable structures or insufficient safety margins. In such cases, long term even life-long pharmacological treatment with benzimidazoles is necessary. It is of great important using image techniques to detect and monitor the changing patterns of biological activities of inoperable HAE before and after the chemotherapy. The combination of PET/CT with SUV value and serology EM18 antibody of patients was as the gold standard to evaluate the metabolic activities of inoperable HAE lesions, which was widely used in HAE patients in western developed countries. However, those methods are not applicable for Chinese HAE patients due to their high cost and complicated processes. Based on previous findings, this succeeding research selected three different MRI sequences including T2 weighted image(T2WI),diffused weighted image (DWI) and dynamic contrast-enhanced (DCE) with their corresponding quantified indicators, including T2 value, ADC value and Ktrans value, to evaluate the biological activities from following aspects: alveolar structure of parasite, secondary inflammatory fibrosis hyperplasia and microcirculation state. As a comparative study, the gold standard of HAE lesion activities were achieved by combining PET/CT with serology EM18 antibody of patients. Three MRI sequences together with gold standard examinations were repeatedly performed at the diagnosis of the diseasee, 6 and 12 months after the chemotherapy. A series of comparative studies were performed among different techniques and indicators, and also，in different stages of treatment. The purpose of this study is to screen one or more MRI techniques and their corresponding indicators for detecting and monitoring the activities of inoperable HAE, and also, to demonstrate the different changing patterns of upper three biological activities of this disease before and after chemotherapy. Those maybe offer a safe, economical and effective MRI technique for evaluating chemotherapy efficiency and deliberating the mechanism of new drugs on inoperable HAE.

临床上70%以上的肝脏泡球蚴病（HAE）因肿块巨大或侵犯了重要组织结构而成为不可切除性病灶，需要长期乃至终身口服苯并咪唑类药物治疗。评价治疗前后病灶的生物学活性变化规律具有重要意义。目前国际使用的结合PET/CT与血清抗EM18评价不可切除HAE代谢活性变化的方法对我国患者并不适用。本课题在既往研究的基础上使用三种MRI序列（T2WI，DWI以及DCE）、选用三个量化指标（T2值、ADC值和Ktrans值），分别从三个不同角度（寄生虫自身囊泡结构、继发的炎性纤维组织增生和微循环灌注状态）反映HAE病灶的生物学活性，以PET/CT结合抗EM18为金标准，在治疗前、治疗后6个月、12个月将各项指标进行对照研究，筛选能敏感反映HAE代谢活性变化的MRI序列及指标，对该病治疗前后不同生物学活性特征的变化规律进行评价，为不可切除HAE的疗效评价及今后研发新药作用机制提供安全、经济、有效的影像学方法。

临床上70%以上的肝脏泡球蚴病（HAE）因肿块巨大或侵犯了重要组织结构而成为不可切除性病灶，需要长期乃至终身口服苯并咪唑类药物治疗。而病灶治疗前后的生物学活性变化规律并不明确。本研究发现未经治疗的AE病程变化有以下的特点：早期表现为实性结节，在生长过程中，有一小部分病灶因某些原因发生大片液化坏死，形似囊肿，此时易合并感染及严重胆道并发症而被发现,其余大部分实性病灶则以相对隐匿的方式缓慢生长，其间可出现部分坏死及少量钙化，最终发展为晚期巨大病灶。HAE作为乏血供病变，DCE-MRI各定量指标对病灶生物学活性判断的价值有限。在治疗前后活性变化的影像学评估研究中，通过比较研究显示DWI能有效的判断泡性包虫病边缘活性区域并与PET/CT之间存在较好的一致性。对于治疗后DWI较PET/CT能敏感的显示活性变化，而对于完全失去活性的病灶二者的比较尚需要更长期的随访研究。