非血流动力学响应函数分析的BOLD fMRI评价胶质瘤组织氧含量的变化机制

脑胶质瘤氧增敏放疗的临床效果并不如头颈部肿瘤那样显著，故了解治疗前、后活体胶质瘤组织内氧含量的动态变化及发生机制尤为重要。在利用Carbogen（CO2/O2混合气体）吸入的BOLD fMRI技术评价肿瘤旁脑组织血管反应性的已有工作基础上，拟建立一种非血流动力学响应函数分析的图像后处理算法，对活体胶质瘤组织内的潜在氧合区域进行无创、可重复地检测与监测。先利用大鼠胶质瘤模型，对照组织生物学检查结果，从功能影像学、组织生物学等角度，观察不同剂量、不同分割方式辐照后瘤体内潜在氧合区域的动态变化特征，评估其与肿瘤增长的关系，了解其发生机制。再初步评价该功能影像学技术遴选适合氧增敏放疗的胶质瘤患者的临床应用价值。本项目研究成果不仅可为胶质瘤放疗的个体化计划与实施，提供临床易用的影像学检查新手段及有益的功能影像学参考依据用以提高疗效，同时也为肿瘤氧增敏治疗机制的深入研究提供"生物信息可视化"途径。

Clinical trials revealed that the effect of oxygen-sensitized radiotherapy in patients with glioma was not as significant efficient as in patients with head and neck neoplasm. Hence, understanding the oxygenation dynamic change within the glioma parenchyma before and after treatment is thought to be crucial to the effectiveness of oxygen-sensitized radiation treatment as well as the clinical outcome for these patients. A blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) technique, using carbogen (CO2/O2 gas mixture) inhalation and a non hemodynamic response function (HRF) analyzed image post-processing algorithm derived from previous research work for assessing cerebrovascular reactivity in the vicinity of brain tumor, would be developed for in vivo non invasive monitoring of the potential re-oxygenation area within the glioma. After identifying the reliability via C6 glioma rat models in comparing with the histopathological and immunohistochemical measurements such as tumor microvessel density (MDV), the expression level of tumor vascular endothelial growth factor (VEGF) and that of oxygen deficient induced factor - 1α (HIF-1α), this fresh functional imaging approach would be optimized, then be applied for investigating the tumoral oxygenation change in the course of radiotherapy, which would be performed with various dose and different fraction modes according to clinical practice. Combined with the functional imaging measurements representing indirectly the internal tumoral oxygenation dynamic change and the ones of the histobiological examinations mentioned above, the mechanism of the internal tumoral oxygenation and the relationship with tumor progression evaluated by tumor size and the survival time could be probed prospectively. Then, the selection of patients with glioma that is suitable for oxygen-sensitized radiotherapy using this functional imaging method should be preliminarily evaluated. The findings of the project may be useful to the individual planning of radiation treatment for improving the therapeutic effect in glioma, by means of developing a functional imaging approach that is able to give the visualized biological information in vivo repeatedly such as "oxygen level topography" in tumor and easier to use in daily clinical practice.