产前三维超声联合功能磁共振、MircroRNAs研究先心病胎儿脑发育异常与损伤

There is a high incidence of brain abnormalities found at birth in babies with CHD in the absence of a defined genetic syndrome. These brain findings may relate to abnormal brain development or brain injury, caused by alterations in the in-utero circulation from the heart defect. Our previous studies also demonstrated brain volume and cerebral blood perfusion abnomalities in fetus with CHD.Yet there is not a detailed evaluation and systematic study of brain development or brain injury in fetus with CHD. The study is expected to fully evaluate fetal brain volume, brain blood perfusion, cerebral metabolism, the development degree of brain cortex and white matter, and hypoxia status in utero in fetus with CHD, using combination of three-dimensional ultrasound, blood-oxygen-level-dependent MRI, proton magnetic resonance spectroscopy, diffusion tensor imaging and MicroRNAs in maternal/cord blood. The purposes of the study are 1) to define initial period of abnormal fetal brain development or brain injury, reveal the extent of brain damage arising from different congenital heart disease, so as to providing evidences for prenatal counseling early intervention and treatment; 2) to identify underlying pathophysiology on the brain structure / function damage in fetus with CHD , by using abortion specimens neuropathological examination and brain tissue/cord blood neurobiology examination, so as to provide new ideas for clinical diagnosis and treatment; 3) to assess systematically parameters changes during the prenatal and infancy period and analyze the relationship with the prognosis, so as to evaluate the clinical neuroprotective efficacy.

高达59％的先心病患儿在新生儿期就已存在脑结构/功能异常，提示先心病患儿神经系统异常可以追溯到胎儿期。我们的前期研究也初步证实先心病胎儿在产前出现颅脑容积和脑血流灌注的异常。目前尚无先心病胎儿脑发育或脑损伤的详细评估和系统研究。产前联合应用三维超声、血氧水平依赖-功能磁共振、氢质子磁共振波谱、扩散张量成像和母血/脐血MicroRNAs有望全面评价先心病胎儿宫内脑容积、脑血流灌注、脑生物代谢水平、脑皮/白质发育和脑缺氧程度，以期筛查神经系统发育异常和脑损伤，明确先心病胎儿脑发育异常或脑损伤发生的初始时间，揭示不同类型先心病所产生的脑损伤程度，为产前咨询、临床及早干预和治疗提供依据；结合引产标本的神经病理学、脑组织MicroRNAs和相关神经损害标记物检查，系统追踪各参数在婴幼儿期的变化以及分析其与预后的关系，以期识别先心病所致脑结构/功能损害发生时潜在的病理生理学机制，为临床诊治提供新思路。

高达59％的先心病患儿在新生儿期就已存在脑结构/功能异常，提示先心病患儿神经系统异常可以追溯到胎儿期。该研究产前联合应用三维超声、功能MRI和母血/脐血MicroRNAs综合评估先心病胎儿脑发育程度及有无脑损伤，发现与正常对照组胎儿相比，部分先心病胎儿在中晚孕期出现局部/整体脑容积增长缓慢、脑沟脑回深度变浅、局部/整体脑血流灌注增强、脑血流区域动力学差异，脑代谢NAA:Choline比值减低，同时病理生理方面表现为神经元染色质结构松散、星形胶质细胞数量增多，脐血/母静脉血micRNAs差异表达等。而且这些神经系统发育障碍与先心病先心病类型相关，左心发育不良综合征胎儿脑发育迟缓最明显,随后是主动脉发育不良、完全性大动脉转位和法洛四联症。神经系统发育障碍超声参数如脑沟回深度、全脑灌注血流指数、大脑前动脉阻力指数、大脑前动脉灌注指数和婴幼儿期智力/神经发育落后明显相关。该研究显示产前超声MRI可筛查先心病胎儿神经系统发育障碍和脑损伤，为产前咨询、产时处理、产后及早治疗提供依据，具有较大的社会效益。根据先心病类型对脑发育异常或脑损伤的不同影响程度进行有的放矢的终止妊娠或及早治疗减缓病程，减轻了家庭负担与社会负担，具有较大的间接经济效益。本研究共发表论文11篇，其中SCI 4篇，CSCD论文7篇；获得2016年中南大学医疗新技术成果三等奖一项；共培养硕士研究生5名。