基于多模态磁共振成像及影像组学的鼻咽癌放疗后脑损伤机制研究

Brain injury is unavoidable after radiotherapy for nasopharyngeal carcinoma (NPC), but only a small number of patients may develop radiation encephalopathy or even brain necrosis. Conventional imaging is difficult to detect it early and make a prognosis exactly. It is of great scientific and clinical importance to determine the possible mechanism of radiation-induced encephalopathy, and to identify and treat the potential patients with radiation-induced encephalopathy in the preclinical stage. Recently, we applied multi-modality MR imaging to the brain injury after radiotherapy for NPC patients. We conducted a pseudo-longitudinal study with four radiotherapy time points. We found that there was a “from functional to structural, from near-end to far-end” developmental trajectory of brain injury after radiotherapy for NPC patients. Therefore, based on longitudinal and within-subject design through cerebral anatomy - function - cognition study, we plan to identify post-irradiation cerebral anatomical and functional damage and possible mechanisms, to screen the imaging biomarkers of cognitive impairment for clinical early detecting and treating the potential patients with radiation encephalopathy. The radiomics method will be used to establish the brain injury model after radiotherapy, and to validate the reliability of radiomics to predict the radiation encephalopathy according to follow-up. The goal of the project is to transform the current clinical basic research into future clinical application, and strive to become a routine clinical evaluation method for brain injury after radiotherapy for NPC patients.

鼻咽癌放疗后脑损伤难以避免，但只有部分患者会发展成放射性脑病甚至放射性脑坏死，常规影像学难以早期发现和预测。明确放射性脑病可能的发生机制、在临床前期准确识别和早期治疗潜在的放射性脑病患者，具有重要的科学价值与临床意义。项目组前期应用多模态磁共振技术对鼻咽癌放疗后脑损伤进行了以四个放疗时间点为断面的假纵向研究，发现鼻咽癌放疗后脑损伤具有“从功能到结构，从局部到远端”的发展轨迹。因此，我们计划在纵向研究资料和组内设计的基础上，通过解剖-功能-认知的研究，拟明确放疗后脑解剖与功能损伤的发展轨迹及可能的机制，筛选出对认知功能损害有关的影像学检测指标，为临床前期准确识别和早期治疗潜在的放射性脑病患者提供依据。应用影像组学方法建立放疗后脑损伤模型，并通过随访验证影像组学预测放射性脑病发生的可靠性。项目组目标是将现在的临床基础研究转变为将来的临床应用研究，力争成为临床评估鼻咽癌放疗后脑损伤的常规方法。

本项目通过一个全脑的、基于体素的放疗前后脑结构与功能改变的研究，得到以下一些有价值的结果，包括：（1）临床前期颞叶下部局部脑活动增加可用于监测早期放疗后脑损伤；（2）双侧海马与后扣带回之间的脑功能连接下降是迟发性认知损害的重要原因；（3）脑功能连接破坏是可塑性的，在影像学表现正常的患者中可以恢复，脑白质损伤、变性有迟发、持续和进展等特点，导致患者出现迟发性脑损害和长期的认知功能异常；（4）鼻咽癌放疗后脑损伤具有“从功能到结构，从局部到远端”的发展轨迹。.本项目在纵向研究资料和组内设计的基础上，通过解剖-功能-认知的研究，明确了放疗后脑解剖与功能损伤的发展轨迹及可能的机制。筛选出了鼻咽癌放疗后脑损伤对认知功能损害有关的影像学检测指标，为临床前期准确识别和早期治疗潜在的放射性脑病患者提供了依据，并对可能的鼻咽癌放疗后脑损伤患者加以密切随访或及时治疗。

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