磁共振pH定量成像无创监测胶质瘤乏氧微环境的关键技术研究

Hypoxia-induced abnormally extracellular acidic environment plays a key role in the induction and maintenance of malignant tumor formation and progression. Magnetic resonance (MR) chemical exchange saturation transfer (CEST) imaging provides a novel noninvasive way for glioma microenvironmental pH quantification. However, the existing techniques are challenged with limited spatial coverage, long scan time and inferior quantification accuracy. Herein, we propose a simultaneous multi-slice acquisition scheme for tumor multiple plane imaging within a single radiofrequency excitation. Partially sampling schedule of Z-spectra incorporated with direct saturation correction theory is designed to accelerate CEST imaging. In addition, a three-echo acquisition strategy is developed for concurrent main field inhomogeneity correction and fat contamination suppression to improve pH quantification accuracy. Evolution of hypoxic microenvironment with tumor progression is systematically investigated, and its relationship with molecular pathological characteristics is explored in both rodent model and glioma patients. The study will not only advance CEST pH imaging techniques, offer a state-of-the-art molecular imaging way for dynamic monitoring and effective evaluation of malignant glioma, but also facilitate the clinical translation of the cutting-edge MR imaging technology, which is of great research and clinical importance.

乏氧引发的细胞外异常酸性微环境的诱导和维持是恶性肿瘤形成和进展的关键环节。磁共振化学交换饱和转移（CEST）成像为胶质瘤微环境pH水平的量化提取和无创可视化提供全新分子影像途径，但现有技术在空间覆盖范围、成像速度和定量精度方面均面临巨大挑战。针对上述问题，本项目提出同时多层成像新方法，单次激发即可获取肿瘤多层面信息；发展结合直接饱和校正理论的部分Z谱数据采集策略，降低频谱采集数目，实质性提高成像速度；研发三回波信号采集方式，同步校正主磁场偏移和抑制脂肪干扰，提高pH量化的准确性；开展胶质瘤动物模型以及临床实验研究，明确细胞乏氧微环境随肿瘤演进的动态转变特征及其与分子病理的内在关联。该项目的实施不仅突破磁共振CEST pH成像固有的技术局限，同时为肿瘤的有效监测和准确评估提供可靠的分子影像学新方法，推动前沿成像技术的临床转化，具有重要的研究价值和应用前景。

乏氧引发的细胞外异常酸性微环境的诱导和维持是恶性肿瘤形成和进展的关键环节。磁共振化学交换饱和转移（CEST）成像为胶质瘤微环境pH水平的量化提取和无创可视化提供全新分子影像途径，但现有技术在空间覆盖范围、成像速度和定量精度方面均面临巨大挑战。针对上述问题，本项目开展以下研究工作：（1）首次实现国产磁共振系统CEST成像技术开发，主磁场频率偏移≤±0.5 ppm，射频场发射电压稳定性可控，通过施加非层选射频脉冲损毁移除脂肪信号，体外模型实验证实pH重复性测量相关性R2≥0.94，量化误差≤0.17 pH单位；（2）提出了类稳态成像新理论，开发完成快速2D和3D CEST成像新技术，保证pH理论定量精度的同时成像时间缩短80%以上，实质性解决CEST扫描时间长、成像覆盖范围有限的瓶颈难题；（3）建立直接水饱和校正技术，实现主磁场偏移、脂肪、磁化转移、直接水饱和效应等多重复杂强干扰因素的有效移除，利于微弱CEST信号定量。动物实验证实该方法能够准确鉴别肿瘤组织、坏死区域以及正常脑组织，保证肿瘤微环境定量成像的灵敏度和准确性；（4）构建基于克拉美罗界（CRB）的测度函数，相比常规使用的余弦距离和欧氏距离，能够更加准确地反映成像参数的编码能力，实现CEST pH关键成像参数智能全局优化。（5）开展规模化临床成像研究，证实所开发的CEST成像方法可表征肿瘤级别和IDH突变状态等重要分子功能特征，并可显著提高胶质瘤治疗后真假性进展鉴别能力，为临床胶质瘤精准诊治提供全新的分子影像途径。该项目的实施不仅突破磁共振CEST pH成像固有的技术局限，同时为肿瘤的有效监测和准确评估提供可靠的分子影像学新方法，推动前沿成像技术的临床转化，具有重要的研究价值和应用前景。