乏氧可导致鼻咽癌放疗抵抗，肿瘤乏氧微环境由灌注缺氧和弥散缺氧构成，目前尚缺乏合适的评估手段。本项目将IVIM DWI应用于鼻咽癌乏氧微环境的评估，与BOLD MRI结合，将定量影像参数D值、D*值、f值及R2*值与HIF-1α、VEGF表达水平关联，针对性评价弥散缺氧及灌注缺氧，构建肿瘤乏氧微环境全面立体的评估体系。并基于前期基础，进一步将功能影像参数与实测pO2对照，深入分析离体低氧及活体状态下塞来昔布对鼻咽癌放疗增敏效果，探讨抑制HIF-1α改善细胞氧合状态的放疗增敏分子机制。本项目有助于揭示鼻咽癌弥散缺氧及灌注缺氧的微观体系，阐明以HIF-1α为靶点的放疗增敏调控路径，为定量影像生物指标评价乏氧微环境及预测鼻咽癌放疗敏感性提供理论依据；同时，本项目也为肿瘤乏氧微环境的分类和细化研究提供了良好的思路和研究手段，有望将IVIM DWI作为无创性评估乏氧微环境和监测缺氧靶点治疗的新工具。

The radiosensitivity of nasopharyngeal carcinoma cells is closely related to hypoxic microenvironment which consists of diffusion hypoxia and perfusion hypoxia, and there are currently no effective methods for assessing hypoxic response of tumor cells. BOLD MRI can effectively evaluate tissue oxygen partial pressure by R2* value, and IVIM DWI can get overall diffusion and perfusion information of tumor tissue by measuring D value, D* value and f value, which may be related with hypoxic type of tumor. In the present study, BOLD MRI and IVIM DWI play an important role in depicting longitudinal changes of tumor hypoxic microenvironment, including oxygen partial pressure, diffusion hypoxia and perfusion hypoxia. We attempt to investigate the feasibility of IVIM DWI as non-invasive methods in evaluating the relationship between tumor hypoxia and angiogenesis, as well as the correlation between IVIM DWI parameters and HIF-1α, VEGF, which is generally acknowledged to be correlated with tumor hypoxia. Meanwhile, we endeavor to analyze how celecoxib inhibit HIF-1α expression to improve oxygenation and radiosensitization of nasopharyngeal carcinoma cells in vitro and in vivo. All the results will help to clarify the change process of diffusion hypoxia and perfusion hypoxia. Furthermore, the project will test the possibility and feasibility of quantitative IVIM DWI parameters as independent factor to monitor the hypoxic microenvironment and treatment response, which may serve as a novel research tool in the future.