氧增强MR对非小细胞肺癌瘤血管异质性生态位构建的定量研究

肿瘤微环境选择力决定肿瘤细胞表型适应与生态进化，肿瘤血管生成代表一种重要的生态位构建过程，影响肿瘤进展、转移或耐药。本课题组基于前期肺癌瘤血管构筑及构建组学空间与亚区域特征识别数据模型研究基础上，拟通过氧呼吸挑战的氧增强MR标记非小细胞肺癌模型基线水平及抗血管生成干预前后不同阶段肿瘤血管异质性及缺氧状态，基于氧水平依赖效应有效识别肿瘤内缺氧与非缺氧组织。根据氧呼吸增强区、无增强区及氧呼吸无增强区内有血流灌注缺氧亚区等直接和间接定量肿瘤缺氧状况，寻找评估NSCLC肿瘤微环境及其动态变化的影像学标记。结合扩散加权MR成像定量肿瘤细胞水平变化，以及动态增强MR灌注参数直方图分析方法评估肿瘤的微血管密度及肿瘤组织微循环。通过监测肿瘤亚区血管结构和功能的动态改变，准确定量肿瘤血管正常化“窗口”，从肿瘤血管生态位构建和缺氧角度对非小细胞肺癌生长与转归做出预测，实现依据影像学方法预测肿瘤生物学行为。

The selectivity of tumor microenvironment determines the phenotypic adaptation of tumor cells and ecological evolution. Tumor vessel produced through angiogenesis is an important niche construction, which affects tumor progression, metastasis or drug resistance. The present study based on the early research of the angiogenesis of lung cancer and the construction of omics space and subregional feature data models. We intend to use oxygen-enhanced MR through oxygen breath challenge to detect heterogeneous tumor vessels and hypoxia status in non-small cell lung cancer model at different stages before and after anti-angiogenic therapy. Hypoxic and non-hypoxic tissue in tumor could be effectively identified based on oxygen-level-dependent effects. Tumor regions with contrast-agent perfused and oxygen-refractory signal were distinguished from perfused oxygen-enhancing and nonperfused regions, and then tumor hypoxia status could be quantified. We would finally find bio-markers to assess the dynamic changes of tumor microenvironment. Combining diffusion weighted MRI to quantify the changes of tumor cells and dynamic contrast enhancement MRI method to evaluate tumor microvascular density and tumor microcirculation, the normalization "window" of tumor vascular can be accurately detected by observing the dynamic changes of vascular structure and function. Ultimately，the progression and outcome of NSCLC could be predicted by evaluating tumor vascular niche construction and hypoxia, and the biological behavior of NSCLC predicted by imaging methods.