深低温停循环术中实时术后长期脑功能监测与成像方法研究

Deep hypothermic circulatory arrest (DHCA) is a neuroprotective technique to make cardiothoracic surgery and complex neurosurgery safer but still with risk of brain injury. Intraoperatively monitoring the brain status (neurophysiology activities, cerebral blood flow and tissue perfusion changes) during DHCA is important for brain injury prediction. Pathological and therapy studies of brain injury after DHCA also need brain activity monitoring chronically and in awake/freely moving status. To achieve this object, in this study, we plan to propose a new method for high SNR and high resolution cerebral blood flow imaging based on entropy analysis of laser speckles. Then, a miniaturized device combining EEG monitoring, laser speckle imaging and optical intrinsic signal imaging is developed and applied in intraoperative and postoperative the brain status monitoring with DHCA operation. As an application, the new imaging method and miniaturized device will be used to investigate the pathogenesis of brain injury during and after DHCA. The potential and specific physiological index are also studied for intraoperative brain injury prediction and rehabilitation of brain functions.

深低温停循环是复杂心脏外科和脑外科手术的重要辅助手段，但易引发脑损伤。目前缺乏可实时监测脑部电生理活动、脑皮层血管血流状态和组织灌注情况的方法和装置，阻碍了深低温停循环致脑损伤机理的深入研究，限制了术后脑功能康复的科学评估。本课题拟研究基于散斑熵分析的高信噪比脑皮层血流成像新方法以实现深低温停循环术中术后脑皮层血管血流及其功能性响应的监测。同时拟研制微型脑功能监测与成像装置，集成EEG监测、激光散斑成像和内源信号光学成像功能，实现深低温停循环术中实时术后长期的脑部电生理、脑皮层血管血流和组织灌注等脑功能参数的监测。作为应用，结合大鼠深低温停循环模型研究深低温停循环致脑损伤的机理以及术中脑损伤预警指标和术后脑功能康复评价指标。本课题的研究将为深低温停循环致脑损伤的机理和治疗研究提供新的研究方法和工具。

本项目以高信噪比高分辨率激光散斑成像理论为核心，紧密围绕术中实时术后长期脑损伤成像这个主题，深入到深低温停循环机理研究中。在术中实时和术后长期高信噪比成像方面，我们发展了多模态成像方法，结合内源光信号成像和同步辐射相衬CT成像，优化了术后长期的成像模态。我们研制了散斑结合EEG微型装置、散斑结合内源光成像微型装置、双模态体表灌注成像仪等，既满足了动物实验的研究需要，也满足了临床研究的需要。在此基础上，我们通过大量实验探索建立了稳定的大鼠深低温停循环动物模型，并发现了复循环后脑皮层血管内血流空间模式的紊乱是脑损伤的重要因素。通过同步辐射成像和染色切片发现了其与微血栓形成的关联；在大鼠心脏停搏动物模型中亦发现了脑皮层血管内血流空间模式的紊乱。针对深低温停循环的术中监护，发展了基于散斑τ_c (t)信号包络线动态范围的术中实时监测参数。研究过程中形成的成像技术、算法和硬件还扩展应用到了临床康复评估领域和光学动作捕捉中。