基于医学影像及多生理参数耦合模拟全肺血流动力学在肺高压评估中的虚拟预测研究

Pulmonary hemodynamics is a key factor in the treatment of congenital heart disease (CHD) for surgical design, therapy timing decision and postoperative recovery. Although the studies of pulmonary hemodynamics and the technique of medical treatment were improved over the years, it is still a challenge to avoid the happen of pulmonary hypertension associated with CHD (PH-CHD), which is caused by abnormal hemodynamics of pulmonary circulation. Based on our previous studies, we found if we could know the relationship between pulmonary hemodynamics and PH-CHD, it will be effective to prevent and control the occurrence and development of PH-CHD. ..In previous studies, we investigated the hemodynamic characteristics of pulmonary arteries, the aerodynamic features of trachea and clinical diagnosis of pulmonary hypertension by using the methodologies of medical image-based computational simulation, in-vitro fluid experiments and clinical follow-up researches. According to these studies, we propose to set up a new medical image-based computational simulation system by coupling the analysis of hemodynamics and aerodynamics with considering multiple physiological elements for the three-dimensional investigation of pulmonary circulation. The study will improve the understanding of hemodynamic characteristics and pathological mechanisms of PH-CHD. Based on the relationship between the specific markers related to the injury of pulmonary vascular endothelial and local hemodynamic characteristics, we also expect to establish a noninvasive evaluation method for the diagnosis and prediction of pulmonary hypertension. This will provide more hemodynamic information for patient-specific diagnosis and treatment of PH-CHD.

肺循环血流动力学是先心病手术治疗时机、方式选择及术后恢复的决定性因素。因先心病引起肺血流动力学改变导致的肺高压是先心病治疗中一大难题。准确了解、掌握和预测肺血流变化与肺高压之间的关系，可以有效预防、控制肺高压发生、发展。前期研究中，本团队利用计算血流动力学模拟、流体实验及临床研究，已充分掌握先心病相关肺血流动力学特性及肺高压临床诊疗。在此基础上，本项目拟通过计算血流动力学与计算气流动力学联合仿真，建立基于医学影像及多生理参数耦合模拟全三维肺血流动力学计算研究体系，用以分析肺高压不同病理病因下血流动力学变化机制、表现形式及规律。结合肺血管内皮损伤特异性标志物与血流动力学改变之间的内在联系，构建个体化无创肺高压预测评估方法，为其防治及改善提供参考。

先天性心脏病相关性肺高压（Pulmonary hypertension related to congenital heart disease, PH-CHD）是肺循环血流动力学异常所致的一种疾病，长期异常的肺血流动破坏血管内皮细胞结构和功能，使肺血管发生不可逆性病变，甚至导致右心衰竭和死亡。因此，明确PH-CHD患儿肺循环血流动力学特性，有助于揭示影响PH-CHD发生发展的血流动力学机制，从而从根源上控制、改善和治疗PH-CHD。本课题利用计算流体力学构建肺循环血流动力学计算研究体系，探索不同病理病变及发展阶段下肺循环血流动力学特性，并结合肺血管内皮损伤，探索其相互之间的联系，寻找可用于PH-CHD无创性诊断评估的方法，以期为临床诊疗提供参考。.课题按照研究计划顺利开展，研究结果显示PH-CHD患儿主肺动脉增粗，肺动脉入口流量和分支流速升高，血管壁面切应力（Wall shear stress, WSS）, 体表面积标准化能量损失（Normalized energy loss, N-EL）在不同病程PH-CHD模型中存在明显差异，N-EL与肺血管直径及流量密切相关，并且在PH-CHD的诊断中价值较高（AUC = 0.90, p = 0.002, 敏感性80%，特异性90%，Cutoff值66.91 mW/m2）。此外，PH-CHD患儿外周血循环内皮细胞（Circulating endothelial cells， CECs）和内皮素-1（Endothelin-1, ET-1）明显高于正常组和PH-CHD疑似组，外周血内皮型一氧化氮合酶（Endothelial nitric oxide，eNOS）在PH-CHD确诊组和疑似组明显升高，与正常组有统计学差异。PH-CHD不可逆组外周血CECs明显高于可逆性组；ET-1和eNOS在两组间无明显统计学差异。ROC曲线显示危险分层评分对PH-CHD诊断价值较高（AUC = 0.770, p = 0.002, 敏感性100%，特异性62.2%，Cutoff值0.088‰）。研究结果表明这些血流动力学因素与PH-CHD进展密切相关，是其临床无创性评估的潜在血流动力学指标。

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