心脏MR多模态成像评价猪心肌缺血再灌注后局部铁沉积介导的心肌损伤及其机制研究

In the setting of acute ST-segment-elevation myocardial infarction, reperfusion injury following revascularization could give rise in microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). Both of them are the sources of iron deposition within the infarct zones, which leads to the prolonged myocardial inflammation and adverse remodeling. Our previous study has indicated that the extent of myocardial injury was tightly associated with regional myocardial function and functional improvement in myocardial infarction, however, the relationship between the proinflammatory factor of regional iron burden and myocardial geometry, structure and function on a regional and global level remains to be determined. We hypothesized that the iron burden plays a role in the myocardial functional and structural abnormality through regulating the activity of myocardial inflammation, fibrosis and apoptosis, as well as the mediated myocardial injury. In this study, we plan to perform multi-modality cardiac MR imaging to investigate the correlation between regional iron burden and extracellular volume, left ventricular strain and functional improvement in the infarct zone, peri-infarct zone and remote myocardium. Meanwhile, in combination with the marker of serology, histology and molecular biology, we probe into the mechanism of myocardial damage mediated by residual iron following acute myocardial infarction. This study could provide the pathophysiological insights and clinical implications of reperfusion-induced regional iron deposition, and we hope a new approach could be developed for the assessment of clinical outcome, effective intervention and the evaluation of drug efficacy.

在急性ST段抬高型心肌梗死中，梗塞相关动脉开通后的再灌注损伤可导致微血管阻塞和心肌内出血。二者是心梗后局部铁沉积的主要来源且能够持续介导心肌炎症并导致心肌不良重构。我们前期研究发现心梗后心肌损伤程度与该区域的局部心功能和功能恢复率密切相关，但是急性心梗后铁负荷量这一致炎因素对心脏局部及整体水平的形态、结构和功能的影响目前尚不清楚。本项目提出心梗后的心肌铁负荷量可通过调控心肌炎症、纤维化和心肌凋亡的强度，介导心肌损伤，对心脏局部和整体的功能、结构改变产生作用这一假说。拟用心脏MR多模态成像，来研究局部心肌铁负荷量与梗死区、梗死边缘区和非梗死区的细胞外容积值、左心室应变及心功能恢复间的关系，同时结合血清学、病理学及分子生物学指标，探讨心梗后心肌铁沉积介导心肌损伤的机制。该项研究为揭示心梗后铁沉积的病理生理意义提供了科学依据，并有望为评估患者的预后、有效干预疾病及监测药物的疗效开辟新的途径。

伴随着急性冠脉综合症治疗的重大改进，急性心肌梗死后的死亡率显著下降，除梗死面积外，心梗后局部心肌的损伤程度、心肌炎症反应、各心肌定量参数都有望成为临床行之有效的终点指标。本研究纳入成功行PCI再灌注治疗的急性ST段抬高型心肌梗死患者及其他冠状动脉疾病患者，研究心脏MR成像技术定量局部和整体心肌损伤、评估炎症反应及预测功能恢复的价值，为其临床转化奠定科学依据。本研究发现自由呼吸下的BLADE刀锋技术和运动校正的LGE序列可更好显示心肌水肿和纤维化。BLADE序列的SNR与CNR和TSE-T2WI相比，差异无统计学意义(p>0.05)，而BLADE序列的图像质量评分均高于后者(p<0.05)。自由呼吸运动校正的LGE序列的图像质量评分和CNR均高于常规屏气LGE序列（p<0.001）。细胞外容积（ECV）可定量局部心肌损伤程度，可用作评估心梗治疗后局部收缩功能恢复的独立预测因子（OR=0.83，95%置信区间：0.77-0.89，p<0.001）；同时心肌整体ECV值与随访EF及EF变化率呈负相关，且亦是后两者的独立预测因子（p<0.005）。采用心肌追踪成像技术获得病变区和非病变区的心肌应变参数。联合冠状动脉MRA成像可提供罪犯血管的冠脉狭窄信息，通过采用双剂量钆布醇增强的梯度回波序列和舌下含服硝酸甘油冠状动脉成像提高CNR和诊断效能。上述研究结果表明心脏MRI技术对于显示梗塞介导的心肌水肿/炎症反应，定量心肌损伤程度，评价心肌局部和整体的组织学、形态学和动力学变化，具有良好的临床转化前景，并为评估患者的预后、有效干预疾病及监测药物的疗效开辟新的途径。但研究也发现，定量技术影响因素繁多，同时由于急性心梗后多种病理生理学改变同时共存且动态变化，对心肌病变的定量参数的解释尚需进一步研究。