基于多模态MRI的神经节苷酯对鼻咽癌放射性脑损伤早期干预疗效的研究

Radiation-induced brain injury is one of the most serious complications of radiotherapy treatment in patients with nasopharyngeal carcinoma. Early intervention by using ganglioside can improve the patients' cognitive impairment effectively. However, fundamental evaluation for early intervention by using ganglioside was few reported, resulting in poor measurement of intervention effect after radiotherapy. Our previous work had found that radiotherapy can cause radiation-induced white matter microstructure damage, gray matter volume decreases and resting-state brain function abnormalities. Thus, we are hypothesizing that there exist unknown mechanism in recovering of the abnormal brain structure and function after early intervention by using ganglioside in the patients with radiation-induced brain injury. In this proposal, monosialotetrahexosylganglioside (ganglioside GM1) will be used to treated radiation-induced brain injury of the nasopharyngeal carcinoma patients during the period of radiotherapy treatment. Meanwhile, multimodal MRI, including diffusion tensor imaging (DTI), high-resolution three-dimensional T1WI, blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in resting state and Cognitive Abilities Screening Instrument (CASI) are combined together to follow up them at the time before radiotherapy, 3 months, 6 months and 12 months after radiotherapy, respectively. The change of white matter diffusion characteristic value, gray matter volume and regional homogeneity of resting-state fMRI in those patients who received early treatment using ganglioside GM1 will be assessed quantitatively. Then, the effect of early intervention using ganglioside GM1 on the radiation-induced brain structural and functional injury in those patients will be investigated. Also, we will sough to find a biomarker to reflect the curative effect of ganglioside GM1. The purposes of this proposal are to provide fundamental imaging basis for the establishment of intervention strategies, curative effect evaluation and prognostic judgment in those patients who received early treatment using ganglioside GM1.

放射性脑损伤是鼻咽癌放疗后最严重的并发症之一，神经节苷脂早期干预能够有效改善其所致认知功能损害。但临床仍缺乏神经节苷脂早期干预的客观依据及疗效评价的客观指标。我们前期研究表明鼻咽癌放疗后存在脑白质微结构、灰质容积及静息态脑功能的损害。由此，我们提出神经节苷脂的早期干预可能能使这些大脑结构及功能的损害得以改善的科学假设。本项目拟对鼻咽癌患者在放疗期间采用单唾液酸四己糖神经节苷酯（GM1）进行早期干预，结合扩散张量成像、高分辨率T1WI、静息态脑功能成像技术对其在放疗前、放疗后3个月、6个月及12个月进行动态随访，定量评估GM1早期干预对患者脑白质扩散特征值、脑灰质容积与脑功能局部一致性的改变情况，深入分析GM1早期干预对鼻咽癌放疗后大脑结构及功能损害的改善情况，并寻求反映干预疗效的生物学标记，以期为其干预策略制定，干预疗效评估及临床预后判断提供客观的影像学依据。

放射性脑损伤是鼻咽癌患者放疗后最严重的并发症之一，以往研究表明神经节苷脂早期干预能够有效改善其所致认知功能损害，但临床仍缺乏神经节苷脂早期干预的客观依据及疗效评价的客观指标。通过多模态神经影像学技术，本研究探讨及比较鼻咽癌患者放疗期间采用单唾液酸四己糖神经节苷酯（GM1）早期干预及未采用GM1干预情况下的大脑功能及结构在12个月内的变化情况。我们的研究结果表明：1、鼻咽癌放疗后大脑功能及结构变化主要表现在：（1）鼻咽癌放疗后患者颞叶脑区局部自发神经元活动变化模式是升高-减低-升高，双侧海马的默认网络功能连接先减低后升高，放疗后3个月即存在组内及组间脑网络功能连接的异常；（2）鼻咽癌放疗后双侧胼胝体压部白质微结构进行性损伤；（3）鼻咽癌放疗后灰质结构的损伤主要发生在晚期延迟反应期，表现多发脑区的皮层厚度的增加。2、GM1干预对于鼻咽癌放射性脑损伤的恢复效应主要表现在：（1）放疗后3个月GM1干预组海马-双侧舌回功能连接升高，提示早期的GM1干预有可能对放疗相关的海马功能连接损害起一定的恢复效应；（2）放疗后6个月GM1干预组左侧扣带角束各向异性（FA）值减低程度有减轻趋势，提示GM1干预有可能对放疗相关的海马纤维束损害具有一定的保护作用；（3）放疗后12个月GM1干预使患者在颞叶灰质容积减低，推测可能与减轻患者间质性水肿有一定的关系。综合上述，鼻咽癌放疗后大脑功能及结构的变化是动态及复杂的，鼻咽癌放疗期间采用GM1干预在一定程度上改善鼻咽癌患者放疗相关的脑功能及结构的损害，对其功能的改善主要表现在早期效应，而对结构损害的保护有可能表现在晚期效应。本研究表明多模态MRI技术能够敏感地检测出早期放射性损伤的动态变化，并为GM1早期干预的策略制定及疗效评价提供了客观的影像学依据。