联合结构和功能MRI研究甲状腺相关性眼病视神经病变的视路损伤及脑部改变

Dysthyroid optic neuropathy(DON) has long been recognized as the most feared complication of thyroid-associated orbitopathy(TAO), potentially leading to blindness. DON may remain undiagnosed in the ealy stages because of its insidious onset, and visual loss may sometimes be rapid and irreversible. In the current study , we focus on imaging measures of structure, function and neurochemistry of the visual pathway and brain in DON, in order to non-invasively examine the effects of DON on the whole visual pathway and brain, to make inferences about the mechanisms underlying visual damage in DON by correlating MRI measures with clinical symptoms. Comparisons of MRI measures of DON patients in different subtypes and stages, and exploration of injury mechanisms in terms of the above transversal discrepancy, provide potential in individualized diagnosis and treatment. The implement of a vertical comparison of MRI measures between pre and post-treatment based on therapeutic effects, provides a method of investigating therapeutic measures in DON. The evaluation of the relationship between visual damage and brain measures will provide new perspectives on diagnosis and treatment. Further, we plan to analyze the similarities and differences in central nervous system(CNS) imaging changes between DON patients and patients with thyroid functional abnormality without DON, to study the correlation between the CNS MRI structural and functional measures of animal models and histopathological and molecular biological measures ,and to explore the potential association with endocrine disorders and DON, in order to promote effective prevention and cure of DON.

甲状腺相关性眼病(TAO)视神经病变(DON)是TAO最严重的并发症，起病隐匿，早期诊断困难，治疗不及时可致失明。本项目拟结合形态测量、组织特征、生化代谢、白质纤维束微观结构及皮层神经元功能激活和连接等多种MRI成像技术从视路和全脑角度观察DON神经系统受累范围和程度；磁共振观察指标与临床体征的相关分析，探讨DON视觉功能损害机制；结合DON的分型、分期进行分类研究，从组间差异和演变趋势的角度探索DON致病机制和损伤模式，提高DON的个体化诊疗水平；治疗前后的纵向对照研究可以为疗效及进展程度进行客观有效的评价；视路损伤与脑部改变的相关性研究进一步拓展诊疗思路。此外，本项目拟实施的甲功异常不伴DON患者与DON患者神经影像信息的横向对比研究，动物模型MRI与免疫组化及分子生物学技术对照分析将从内分泌紊乱致中枢神经病变的角度探索DON可能致病机制，为DON的有效防治奠定基础。

本课题从基于视神经鞘和视神经表观特征的DON诊断模型建立、TAO与DON患者的全视路DTI、 DON患者的大脑形态学及静息态fMRI研究、大鼠甲亢模型脑部PET-CT和高场MRI研究、TAO患者眼肌纹理特征的提取和分析、基于Cube-flex的定量分析对DON眼眶的病理特征研究、联合T2mapping和T2 IDEAL序列预测TAO疗效共七个方面开展研究。研究结果显示基于IDEAL-T2WI的视神经及视神经鞘的量化分析提供了DON的诊断特征，进一步的影像组学模型显示其临床适用价值高；全视路DTI示DON是以视神经病变为主的全视路损伤，炎性反应可能参与了DON神经损伤的发生，联合DTI多参数诊断DON有较高准确度；DON患者相对TAO，其默认网络脑区和视觉皮层体积均有缩小，视觉皮层的功能活动异常及视觉网络损害；大鼠甲亢模型组各脑区的SUV值均有不同程度降低，高场MRI研究进一步证实双侧扣带回及左侧眶额皮层有损伤；采用直方图分析软件提取眼外肌的T2mapping值，获得与水含量相关的百分数T2值和代表组织异质性的参数，深度挖掘了TAO患者眼肌病变信息，在激素代谢及免疫状态异常的情况下眼肌处于持续受累状态；治疗前眼肌T2mapping直方图参数的nomogram疗效预测模型提示95thT2RT、偏度和熵越大，激素冲击治疗有效性越高；Cube-flex序列的定量分析测量结果显示DON组的眼外肌总容积、眼外肌水肿程度及眶脂肪水肿程度均显著高于非DON组；联合T2mapping和T2 IDEAL序列能有效预测TAO激素冲击疗效，T2RTmean和WFmax是中重度TAO患者激素冲击疗效的独立预测因子。本项目所获成果已全面运用于临床，基于影像学模型的病情判定和疗效预测提高了TAO的诊疗水平，对DON的早诊断、早治疗可显著降低此类患者的致盲率，提高患者生活质量。