长期激素联合免疫抑制剂治疗的激素耐药型肾病综合征儿童认知功能下降的影像学预测研究

Steroid-resistant nephrotic syndrome (SRNS) is one of the commonest primary nephrotic syndromes in children.Its inflammatory response needs to be improved by long-term treatment with glucocorticoid and immunosuppressive agents.However, the neurotoxic effect of glucocorticoid and immunosuppressive agents may affect the development of the central nervous system in children, resulting in cognitive decline. This current project aim to use the longitudinal experimentaldesign to track the effect of long-term glucocorticoid and immunosuppressive agents treatment on cognitive function in SRNS children. The project used the fourth edition of the wechsler child intelligence scale (wisc-iv) to assess children's cognitive abilities. Subjects whose cognitive scores after six months of treatment with SRNS were defined as "cognitive impairment risk group" (" risk group "). With the magnetic resonance neuroimaging technology, individual differences in brain white matter, gray matter and network topological properties of SRNS children were calculated. At the same time, combined with machine learning algorithm, the negative event of cognitive decline in SRNS during drug treatment was predicted to obtain sensitive and robust imaging markers to predict the risk of cognitive decline. The project was characterized by advanced technical sophistication, great scientific value and high potential of strong clinical application.

激素耐药性肾病综合征（steroid-resistant nephrotic syndrome，SRNS）是儿童最常见的原发性肾病综合征之一，需要通过长期大量的激素联合免疫抑制剂治疗来改善其炎症反应。然而激素类药物的神经毒性作用可能会造成患儿出现认知功能下降。本项目以长期进行激素联合免疫抑制剂治疗的SRNS患儿为研究载体，设计纵向观察实验，探索激素联合免疫抑制剂的使用对SRNS患儿认知功能的影响。本项目根据韦氏儿童智力量表第四版评分标准定义认知功能下降风险组。借助磁共振神经影像技术，探索SRNS患儿大脑白质、灰质、网络拓扑属性的个体差异信息。结合人工智能算法，预测康复治疗过程中SRNS是否出现认知功能下降这一负性事件，并获取敏感、鲁棒的预测认知功能下降风险的影像学标记。本项目的顺利实施可为SRNS患儿康复治疗过程中认知功能下降风险提供更为准确的影像学参考依据，有较高的临床应用前景。

在本项目的资助下，研究成果分为两大部分。首先是研究方法。现有白质分析方法大多基于标量分析，忽略了白质纤维束的方向传导。申请人研究团队提出了基于图谱的白质纤维束分析方法，该方法可以对全脑的白质纤维束进行自动的提取、分割、聚类，可对存在异常的白质微结构进行精确的空间定位和分析。第二部分申请人以终末期肾病患者为研究对象，结合团队的白质微结构分析方法，探索终末期肾病患者认知功能的影响因素，寻找可能的临床生化、透析和影像学预测标记。首先，我们发现无透析治疗的终末期肾病患者白质微结构发生改变，改变的白质微结构可进一步对有无情绪异常的终末期肾病患者进行区分。随后以规律性透析终末期肾病患者、无透析治疗的终末期肾病患者为研究对象，发现透析治疗对终末期肾病患者的中枢神经系统存在有限的保护作用。进一步的，在单个透析单元中，发现透析治疗过程中血压和超滤量与终末期肾病患者认知和中枢功能的改善有关。自项目批准以来，共发表SCI论文7篇，授权发明专利4项。