基于伪连续ASL技术探讨低龄儿童烟雾病脑血流灌注变化与认知功能损伤的相关性研究

Moyamoya disease(MMD) is an important causes of cerebral ischemic stroke in children.Recent studies have showed that the risk of cognitive impairment in children with MMD was higher than the risk in adults patients. One point of controversy is whether the diminished intelligence is due to a secondary condition accompanying MMD or is directly a product of the disease Process. According to reports in the literature and our previous study, cerebral hypoperfusion was related to the cognitive dysfunction in adults patients with MMD. At present, there are very few studies about the characteristics of cerebral hemodynamics in younger children with MMD due to the small age and consideration of effect of the radiation exposure.The relativity between the abnormal perfusion in regional brain and cognitive impairment in younger children remains unclear. Arterial spin-labeling(ASL) is a well-established method for the assessment of cerebral vascular disease. It does not require the injection of an exogenous contrast agent and have no radiation exposure. Our previous study found that there is a correlation between perfusion data from ASL and CT perfusion imaging in adult patients with MMD. In this study，pseudo-continuous ASL 3.0T MR protocol was applied on younger children with MMD. We investigate characteristic of distribution of cerebral vascular arteries and cerebra perfusion and study the relativity between abnormal cerebral perfusion and cognitive dysfunction . This research work is expected to provide a safe and noninvasive technique in evaluation of cerebral perfusion and nerve function in children with MMD. This method will provide a reliable objective evidence about the mechanisms of cognitive dysfunction in MMD.

烟雾病是儿童缺血性脑卒中的重要病因，研究显示儿童病人认知功能障碍的风险高于成人。认知功能障碍是烟雾病继发病还是烟雾病发展过程中直接导致尚不清楚。文献报道和我们前期研究显示脑血流低灌注和成人患者认知功能障碍有关。考虑年龄因素和放射暴露对生长发育的影响，目前有关低龄儿童烟雾病脑血流动力学研究偏少，其局部脑组织血流灌注异常和认知功能障碍的相关性尚不清楚。研究显示，动脉自旋标记（ASL）成像技术具有无创和无放射的优点，我们前期工作发现伪连续ASL在成人烟雾病脑灌注评估中具有很好匹配性。本课题采用伪连续ASL成像技术，研究低龄儿童烟雾病的脑血管分布和脑血流灌注特点，并在此基础上开展个体化血管重建术，通过手术前后对认知功能的测评，探讨低龄儿童烟雾病局部脑血流灌注异常和认知功能障碍的相关性。研究实施不仅为低龄儿童烟雾病的术前评估提供一种安全可靠的方法，同时为探寻烟雾病认知功能障碍病因提供早期客观依据。

目前对于低龄儿童烟雾病病人脑血流灌注缺乏无创评价，其不同脑区脑组织血流灌注不足和特定类型的认知功能障碍是否相关尚不明确。本研究选择无创伪连续动脉自旋标记（pCASL）技术评估低龄儿童烟雾病的脑组织血流灌注特点，同时分析不同脑区脑血流灌注异常和特定认知功能障碍相关性。研究首先对比分析了13例儿童烟雾病患者ASL脑血流影像与CTP脑血流影像和DSA代偿评价的一致性。经定性分析发现，ASL与CTP对灌注异常评价具有显著一致性（κ= 0.398，p <0.001）；基于感兴趣区的定量分析中，ASL与CTP影像中绝对脑血流量值显著相关（r = 0.413，95％CI 0.287-0.525，p <0.001），侧枝血管评价比较中，通过ASL上动脉通过伪影判断侧枝血管与DSA侧枝血管代偿评价间一致性良好（κ= 0.680，p <0.001）。研究进一步对21例患儿进行认知功能测评（韦氏儿童认知量表第4版），入组患者的所有认知指数得分除言语理解指数外均明显低于同年龄组常模均值。存在影像学证实脑梗死病史的患儿，其知觉推理指数（p = 0.019）显著较低。左侧大脑半球的Suzuki分期与总智商呈显著负相关关系（r = -0.452，p = 0.039）。体素水平分析表明，工作记忆指数、加工速度指数、总智商与左侧颞下回、颞上回及顶下小叶部分脑区的脑血流量呈显著正相关关系（p < 0.001）；而基于感兴趣区的分析表明，左侧颞叶、顶叶和枕叶的局部平均脑血流量与工作记忆指数、加工速度指数和总智商呈正相关关系；经过多因素回归分析对混杂因素进行校正之后，左侧颞叶的脑血流量与加工速度指数独立相关（β= 0.535，p = 0.041）。通过本研究我们发现ASL对脑灌注的评估与目前常用措施具有接近的效果，可成为CTP的理想替代者，且具有辅助评估侧枝循环功能，应用于儿童烟雾病临床评估十分具有前景。对于儿童烟雾病认知功能和脑血管灌注的相关性研究我们发现儿童烟雾病患者中多数表现出不同程度的认知功能障碍，存在脑梗死病史的患儿知觉推理能力明显较差。左侧颞叶的平均脑血流量独立于其他临床混杂因素，与认知过程的处理速度独立正相关。