基于体素内非相干性运动的磁共振扩散加权成像评价肺腺癌抗血管生成疗效的研究

Antiangiogenic therapy is a new way of treatment for advanced lung cancer. How to promptly and accurately evaluate the efficacy and predict the prognosis is still one of the most important challenges. The objective of this study is to test whether parameters derived from intravoxel incoherent motion diffusion weighted MR imaging (IVIM-DWI) can be evaluated on antiangiogenic therapeutic efficacy in patients with advanced pulmonary adenocarcinoma. Firstly, IVIM-DWI-derived parameters (true diffusion coefficient D, pseudodiffusion coefficient D*, perfusion fraction f ), dynamic contrast-enhanced MRI-derived parameters and pathological changes after antiangiogenic therapy were compared and evaluated the correlation between these quantitative parameters. Secondly, the diagnostic value of IVIM-DWI-derived parameters was evaluated in the quantitative assessment of the antiangiogenic therapeutic and traditional chemotherapeutic efficacy in patient with advanced pulmonary adenocarcinoma. Finally, we also test WHO, RECIST, mRECIST and IVIM-DWI parameter values as surrogate markers of response and correlated with survival after antiangiogenic treatment in patient with advanced pulmonary adenocarcinoma to identify differences in radiologic assessment methods and determine optimal imaging criteria for response evaluation in advanced pulmonary adenocarcinoma patients treated with antiangiogenic inhibitor. Our study might provide early novel imaging biomarkers of tumor response induced by targeted molecular therapy, which are important in determining treatment success, identifying complications, and guiding future therapy.

抗血管生成治疗已成为晚期非小细胞肺癌最重要的全身治疗手段之一，并已取得较好的疗效，但如何及时、准确地评价疗效及判断预后是亟需解决的难题。本课题拟运用体素内非相干性运动磁共振扩散加权成像（IVIM-DWI）技术评价肺癌抗血管生成疗效，通过与DCE-MRI对照，探讨IVIM-DWI影像生物学标记物真扩散系数D、假扩散系数D*和灌注分数F评价肺腺癌抗血管生成疗效的可行性，阐明治疗前后相关参数变化的组织病理学基础，初步建立IVIM-DWI评价标准；在此基础上通过前瞻性研究比较IVIM-DWI标准评价肺癌抗血管生成治疗和传统化疗疗效的效能差异，进一步验证IVIM-DWI标准评价抗血管生成疗效的临床意义；最后，通过与现行临床评价标准（WHO、RECIST1.1和mRECIST标准）对照，探讨IVIM-DWI影像生物学标记物评价进展期肺腺癌抗血管生成疗效和判断患者预后的重要临床价值。

抗血管生成治疗已成为晚期非小细胞肺癌最重要的全身治疗手段之一，并已取得较好的疗 效，但如何及时、准确地评价疗效及判断预后是亟需解决的难题。本课题运用体素内非相干 性运动磁共振扩散加权成像（IVIM-DWI）技术评价肺癌抗血管生成疗效：（1）分析了45例患者（男29 名、女16 名, 平均年龄57.9±9.7岁）的IVIM-DWI数据，比较单指数模型DWI参数ADC和双指数模型IVIM-DWI参数D、D*和f在评价非小细胞肺癌化学治疗疗效中的价值。结果发现，与治疗前相比，治疗后诸参数（ADC、D、D*和f）均上升，但差异无统计学意义（t-test, all P>0.05）。治疗有效组治疗前后ADC和D变化值均大于无效组（p<0.05），而f和D*变化值差异没有统计学意义（p>0.05）。D变化值用于评价疗效的效能最大（AUC 0.764），诊断敏感度为96.7%，特异度为60%；以ADC和D变化值功能MRI指标早期评价疗效，有效组和无效组患者PFS差异有统计学意义（log-rank test, P=0.001和P<0.001），而基于RECISST1.1标准评价的结果患者间的PFS差异无统计学意义（log-rank test, P=0.107）。治疗后肺癌ADC变化值（cox model，HR (95% CI)：0.351(0.185, 0.668)，p=0.001）和D变化值（cox model，HR (95% CI)：0.142(0.057, 0.356)，p<0.001）是患者PFS的独立影响因子。（2）利用MaZda软件回顾性分析41例接受抗血管生成治疗的非小细胞肺癌患者共41个病灶的治疗前D map 图像纹理特征，探讨基于治疗前D map肿瘤图像纹理特征预测非小细胞肺癌抗血管生成疗效的可行性。在Fisher、MI和POE+ACC法提取的3组特征纹理中，有效组和无效组间的纹理特征参数Horzl_GLevNonU (0.11±0.09 vs. 0.05±0.07，p=0.013)、135dr_GLevNonU（128.1±10.2 vs. 135.3±9.9，p=0.040）和Teta3（0.64±0.16 vs. 0.82±0.13，p=0.001）3个参数差异有统计学意义。以POE+ACC法提取的特征纹理进行非线性判别分析法分类效能最佳（AUC = 0.79