基于神经影像特征的额叶胶质瘤患者术后谵妄预测模型的构建与初步临床应用研究

Recent studies have shown that the abnormality of brain structure and networks might be neural substrates of vulnerability to postoperative delirium (POD). Our previous clinical research found that the incidence of POD in glioma patients was much higher than that of patients with other intracranial lesions and was associated with poorer cognitive function prognosis. We speculated that exploring preoperative neuroimaging characteristics contributed to predict the risk of postoperative delirium. However, the neuroanatomical foundation of POD in glioma patients has not yet clear. Frontal glioma patients will be enrolled. All patients will undergo the standardized clinical interviews, comprehensive neuropsychological assessments and APOE genotyping. At the same day, multimodal Magnetic Resonance Imaging (MRI) (including 3-dimentional structure, blood oxygen-level dependent for cortical activation and diffusion functional MRI) will be performed to explore the pre-operative brain structure and networks. POD will be evaluated on postoperative day1-3. We aim to explore the neuroanatomical foundation of POD in frontal glioma patients from the level of brain structure and networks, as well as integrate cognitive index with neuroimaging characteristics by event-based probabilistic model (EBM). Then we will assess the optimal sequence of POD risk events occurrence, which will be defined as postoperative DElirium Risk Events in patients with FROntal lobe Glioma index (DERE-FROG index). We will develop the DERE-FROG index to measure risk stage and then applied the DERE-FROG index to distinguish individuals who progress to POD from those who did not. At the same time, we will also build specific risk model for subgroups according to APOE genotyping and brain reorganization situation. The project will have important implications for the prevention of POD in frontal glioma patients.

近期研究表明，术前脑结构与脑网络异常可能是术后谵妄的神经解剖学基础。前期研究显示胶质瘤患者术后谵妄发生率显著高于其他颅内占位，且与更差的认知功能预后相关。我们推测，探索该群体术前神经影像特征有助于预测术后谵妄风险。但该人群术后谵妄的神经解剖学基础未明。本研究将选取额叶胶质瘤患者，于术前评估神经认知功能，检测APOE基因型，同时行3D结构像，皮层血氧水平依赖成像（静息态+任务态）、皮层下弥散张量多模态磁共振以探索术前脑结构以及脑网络情况，并于术后1-3天评估术后谵妄。旨在从脑结构与网络连接层面探究该人群术后谵妄的术前神经解剖学基础，并通过事件概率模型融合认知指标及神经影像学标记，构建系列标记物发生异常的最佳顺序，从而预测患者的风险度，同时再根据患者不同APOE基因型以及神经功能代偿建立与否,分别建立更有人群特异性的亚组预测模型，最后行小样本临床验证，为额叶胶质瘤患者术后谵妄的预防提供依据。

近期研究表明，术前脑结构与脑网络异常可能是术后谵妄的神经解剖学基础。前期研究显示胶质瘤患者术后谵妄发生率显著高于其他颅内占位，且与更差的认知功能预后相关。我们推测，探索该群体术前神经影像特征有助于预测术后谵妄风险。但该人群术后谵妄的神经解剖学基础未明。本研究将选取额叶胶质瘤患者，于术前评估神经认知功能，同时行3D结构像，皮层血氧水平依赖成像（静息态）、皮层下弥散张量多模态（DTI）磁共振以探索术前脑结构以及脑网络情况，并于术后1-3天评估术后谵妄。旨在从脑结构与网络连接层面探究该人群术后谵妄的术前神经解剖学基础，并通过融合认知指标及神经影像学标记，构建术后谵妄风险预测模型。研究结果发现，基于体素的形态学分析提示：无论额叶胶质瘤位于左侧还是右侧，肿瘤对侧的背外侧前额叶皮质（DLPFC）的灰质体积都与术后谵妄发生的风险呈负相关；DTI结果提示：无论额叶胶质瘤位于左侧还是右侧，双侧胼胝体膝部的各项异性（FA)亦与术后谵妄发生的风险呈负相关。并且偏相关性分析发现肿瘤对侧的DLPFC的灰质体积与胼胝体膝部的白质完整性呈正相关。结果提示DLPFC脑区的代偿可能参与调控额叶胶质瘤患者术后谵妄的发生，并且这种对侧代偿可能是通过胼胝体介导的。最后我们运用广义线性模型构建该人群术后谵妄的风险模型，发现术前认知功能以及肿瘤对侧DLPFC脑区灰质体积是术后谵妄发生的重要危险因素。本项目为额叶胶质瘤患者术后谵妄的预防提供重要依据。