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

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。

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.