基于“S-CEUS+U-CEMRI+SWI”的影像联合策略对肝癌微血管侵犯早期诊断的研究

微血管侵犯是肝癌复发的高危因素，但目前存在无术前准确诊断方法的问题。国内外研究发现部分肝癌在Sonazoid造影剂的超声造影（S-CEUS）和USPIO对比剂的增强磁共振（U-CEMRI）上有癌旁异常灌注/强化，猜测可能是微血管侵犯区。但申请人的预实验发现：不同影像学癌旁异常的检出率和位置有差异。申请人前期研究发现发生微血管侵犯的区域微血管密度增高。基于上述发现，本项目创新性地提出“S-CEUS+U-CEMRI+SWI”联合策略诊断微血管侵犯的设想：前两者探查癌旁异常灌注或强化区以降低异质性，磁敏感性加权成像（SWI）计数该区域增多的微血管。为证实该设想的合理性和有用性，本项目从巨噬细胞角度系统阐述和体内外实验证实癌旁异常影像的产生机制；以病理学标准评价联合策略的诊断效率。本项目在方法学上建立了微血管侵犯的早期、无创、准确的影像学诊断体系，为优化微血管侵犯相关的肝癌临床诊疗提供了实验依据。

Microvascular invasion is a high risk factor for recurrence of liver cancer. However, there is a critical problem that no effective method of preoperative diagnosis is available. Domestic and foreign researches have found that some liver cancers have paracancerous abnormal perfusion / enhancement in imaging by contrast-enhanced ultrasound using Sonazoid (S-CEUS) and contrast-enhanced magnetic resonance imaging using USPIO(U-CEMRI) as contrast agents, and speculate that these abnormal imaging may be the area of microvascular invasion. However, in our pre-experiment, it was found that there were discrepancies in the detection rate and location of paracancerous imaging abnormalities. Meanwhile, our previous study found that the microvessel density increased in the area where microvascular invasion occurred. Based on the above findings, this project creatively puts forward the idea of “S-CEUS+U-CEMRI+SWI” combined strategy for the diagnosis of microvascular invasion. That is, using the former two modalities to detect paracancerous abnormalities to reduce heterogeneity, while introduce a new technique of susceptibility-weighted imaging (SWI) to count the increased microvessels in this area to improve the diagnostic specificity. To confirm the rationality and usefulness of this idea, this project systematically elaborated from the perspective of macrophages and confirmed the mechanism of paracancerous abnormal images in vivo and in vitro, while evaluated the diagnostic efficiency of the combined strategy by pathological criteria. This project would establish an early, non-invasive and accurate diagnosis system of microvascular invasion in methodology, which provides an experimental basis for optimizing the clinical diagnosis and treatment of liver cancer related to microvascular invasion.