基于多模态影像学对肝泡状棘球蚴病治疗后演变过程与适时中止服药的研究

Echinococcosis is one of the infectious disease which is under strongly control by our government. As hepatic alveolar echinococcosis(HAE) has the feature of infiltrating growth just like tumor, most patients lost the opportunity of resection when they see doctor. Long-term and even lifelong of albendazole treatment became the only choice for non-surgical therapy HAE， which will lead to liver toxicity, hair loss, dizziness, nausea, neutropenia and even teratogenic effect. Therefore, it is urgent for clinical to look for a suitable non-invasive and accurate imaging technique to evaluate the biological activity change after the drug therapy for HAE, and to provide timely surveillance for the metabolism changes inside the lesion so as to determine the proper treatment course. This study plan to use the three advanced imaging techniques (PET-CT, DWI and MRI spectrum ) to dynamically detect the spectrum changes of glucose metabolism, bisphosphate adenosine, phosphoric acid creatine, Lactic acid and water molecules diffusion in the infected rats model after albendazole liposome treatment, Aiming at evaluating the proliferation ability and metabolism level of the lesion, revealing the rules that HAE treated after giving albendazole liposome, clarifying the mechanism of molecular imaging changes after medical treatment, so that we can offer reliable experimental data and theoretical support for rational guiding drug treatment as well as for the considering to quit albendazole treatment in the right time.

包虫病是国家重点控制的传染病之一。肝泡状棘球蚴病具有起病隐匿和类肿瘤样增殖浸润生长的特点，口服阿苯达唑治疗仍然是目前的主要治疗措施。但是长期服用阿苯达唑会导致肝脏毒性等严重副作用。目前尚缺乏客观评价服药后泡球蚴病灶内部的生物学变化规律的研究。本研究拟采用PET-CT、MRI扩散成像和波谱成像三种先进的影像技术，动态观察感染肝泡球蚴的大鼠给予阿苯达唑脂质体后，病灶内部葡萄糖代谢、二磷酸腺苷和磷酸肌酸及乳酸的频谱、水分子扩散的变化，并以病理标本和相关免疫组化结果做对照，揭示给予阿苯达唑脂质体后肝泡球蚴病内部的影像演变特点与规律；阐明药物治疗后病灶多模态影像学改变的病理基础和机理；比较几种影像技术的诊断效能，为临床合理应用各种影像学技术指导合理用药、评价疗效和指导适时中止服药提供实验数据和理论支撑。

本研究自2013年1月至2016年12月，历时4年。研究目标是为临床合理应用各种影像学技术指导不可切除的泡球蚴患者合理用药、评价其疗效和指导适时中止服药提供实验数据和理论支撑。.课题组按照实验计划建立大鼠泡球蚴实验动物平台，重点分析研究了接种成功后不同时期大鼠肝泡球蚴病灶的MRI-DWI动态影像，并与同期病理改变相对照，揭示了不同时期大鼠肝泡球蚴病灶动态演变的规律，发现 MRI扩散成像成像能揭示泡球蚴病灶从早期到晚期的动态演变过程，病灶内部信号、小囊泡、病灶边缘带都随着分期不同而有不同变化，DWI图像可以清晰显示病灶内部结构和病灶周边的特征性过渡带。随着接种时间延长，病灶内部及周边ADC值逐渐减小，该现象揭示病灶内部及周边纤维化程度逐渐增加。由此可见， MRI扩散加权成像可以动态显示肝泡状棘球蚴病灶周边的纤维化程度，与ADC图像两者结合可以动态反映病灶周边血管化和纤维化的动态演变。.基于临床病例，建立在活体即可实现的无创性的多模态影像学检查和评价体系，尝试用MRI扩散成像、能谱CT 取代昂贵的PET-CT来评价泡球蚴的生物学活性。研究发现上述各种方法均能显示病灶边缘浸润带的变化: MRI扩散成像显示病灶内部信号、边缘带的演变加之 MRCP更容易显示病灶内小囊泡的分布数量和信号变化，均能反映病灶侵袭的活性的差别，是临床容易推广应用的最好的技术；能谱CT研究表明碘值与MVD高度相关：碘图显示包虫组织、病变边缘区域组织及正常肝组织碘值存在差异，病灶边缘弧线形或者半圆形高碘值带对应于PET-CT所显示的高代谢摄取区，也可用于显示病灶边缘的侵袭活性，有望作为评价泡球蚴病灶活性的另外一个选择。.