脑动静脉畸形患者运动投射网络重构的解剖连接及功能连接的拓扑学机制研究

Cerebral arteriovenous malformations (AVM), as congenital brain lesion, occur before the formation of motor projection networks. Thus, AVM patients are ideal models for the study of motor projection network remodeling. Till now, the topological mechanism of subcortical motor projection network reorganization in AVM patients, including anatomic and functional connectivity, has not yet been elucidated. Our previous studies showed that AVMs with different sizes and locations could cause different models of motor projection system reorganization, and that were significantly associated with the patient's preoperative and postoperative motor function. Furthermore, the compensatory ability is different in patients with different levels of CST involved. Accordingly, we preliminarily proposed the theoretical model of " motor tree " to predict the possible reorganization modes of motor projection system in different situations. To further explore the reorganization mechanism of motor projection network and to improve the theoretical model of "motor tree", this study is scheduled as follows: First, comparing the anatomic connectivity and functional connectivity, to explore the principle of motor projection network reorganization in AVM patients; Second, comparing the reorganization of motor projection in congenital disease (AVM) versus acquired diseases (low-grade gliomas and stroke), to verify and enrich the theoretical model of "motor tree", including the relationship between the timing of lesion occurrence, the involved level of CST, the degree of dexterity of motor function and motor reorganization; Third, to explore new functional imaging signs correlated with good clinical outcomes after radical resection of the lesions to broaden the indications of radical resection in AVM and tumor patients.

脑动静脉畸形（AVM）是一种先天性的脑内病变，发生早于运动投射网络的形成，是研究运动投射网络重构的理想模型。目前，AVM患者运动投射网络重构的解剖结构连接及功能连接机制尚不清楚。我们的前期研究结果显示：不同大小、部位的AVM可引起运动投射网络不同的重构模式，且与患者术后运动功能相关；不同部位的皮质脊髓束受损，其术后代偿能力不尽相同。据此，我们初步提出了“运动树”的理论模型，即纤维束受损的时间、空间维度均与其重构的潜力及方式相关。为进一步明确AVM患者运动投射网络重构的拓扑学连接机制，完善“运动树”理论模型。本研究拟通过解剖连接与功能连接的对比分析，探索AVM患者运动投射网络重构的规律；通过先天性疾病（AVM）与后天疾病的对比（低级别胶质瘤、脑卒中），从病变发生时机与重构、纤维受损水平与重构、运动精细程度与重构三个维度验证并丰富“运动树”理论模型；探索新的功能影像学标志，预测患者手术预后。

本研究的主要目标在于对术前及术后脑血管畸形患者皮层下运动投射网络变化规律的探索，基于患者术前、术后运动投射网络的变化及特点，结合患者肢体功能术前、术后的评估，确定术前及术后功能缺损的影像学标志，明确脑血管畸形患者病变全切的指征。根据研究方案的评估模式，本研究完成35例巨大脑血管畸形患者的术前评估及术后随访，对每例患者进行术前多模态核磁共振检查评估（BOLD-fMRI, DTI, 3DT1, TOF-MRI），术中运用脑电监测及基于多模态核磁共振的神经导航保护功能脑组织，术后评估患者运动、语言、视野等重要功能，并复查多模态核磁共振各项评估。形成据于DTI和BOLD-fMRI的个体化术前评估模型，并与传统的SM分级进行比较，对于AVM来说，其远期预后预测价值大于SM分级。提出累及皮质脊髓束、弓状束、视辐射等重要纤维的AVM患者临床治疗的病人选择标准，即DTI评分小于等于2分的患者预后在可接受范围（mRS评分0-3分），当症状加重或出血时可以考虑手术治疗，并提供了术前评估及术中导航的可靠模式。提出BOLD评分可能受巨大AVM血流动力学的影响较大，可能产生假的重构现象，临床实践应引起注意，应进行进一步探索。在确定了脑深部血管畸形术前DTI评估对于患者预后的重要性后，如何在术中保护重要纤维束成为关键的问题。本研究再次纳入深部血管畸形患者7名，根据术前DTI显示病变及纤维束所在的部位，运用Endoport引导，选择合适的手术通道，采用功能导航辅Endoport引导神经内镜手术方式进行深部血管畸形切除。平均随访17个月之后，仅一名患者术后出现对侧体偏瘫，6个月随访肌力恢复至3级，术后致残率仅为14.3%，远远低于文献中的30-50%。分析比较术前术后CST的FA值，我们发现术前平均FA值为0.45，术后平均FA值为0.46，配对样本T检验提示手术前后无差异p=0.29，提示手术未明显损伤CST；比较术前术后CST的纤维数量，我们发现术前平均值为413，术后平均值为510，配对样本T检验提示手术前后无差异p=0.28，提示手术未明显损伤CST。研究结果具有较强的临床转化及运用价值。