非对比剂增强负荷 T1 mapping 成像评估心肌缺血/存活/梗死的动物实验研究

In view of the limitations of traditional contrast-enhanced myocardial stress perfusion and gadolinium delayed enhancement in assessing myocardial ischemia / viability in coronary heart disease and the cost of contrast agents and related safety issues, based on the previous work of the applicant, the purpose of this study is to evaluate the feasibility and accuracy of non-contrast stress T1 mapping in the detection of myocardial ischemia and viability in ischemic heart disease, comparing with the traditional method (contrast enhanced stress myocardial perfusion and late gadolinium enhancement). This randomized animal experiment will carry out in-depth into the application and relative mechanism of non-contrast stress T1 mapping imaging in ischemic heart disease. The research project is expected to clarify the range of T1 threshold and the rate of change in different abnormal myocardium (ischemic myocardium, hibernating myocardium, infarcted myocardium) and normal myocardium by using resting and stress non-contrast T1 mapping imaging. It will further clarify the relationship between myocardial T1 value and cardiac morphology and function and its internal mechanism. This may offer a preliminary understanding of evolutional process of different lesions of myocardium in ischemic heart disease. The results of the project are of great importance for the clinical decision-making of ischemic heart disease in both diagnosis and treatment, especially for evaluating left ventricular remodeling, risk factors stratification and prognosis. It will also provide the related scientific information to basic and clinical research, especially for the mechanism of left ventricular remodeling post infarction, development of targeted drug therapy of inhibiting the synthesis of extracellular matrix.

针对传统对比剂增强药物负荷心肌灌注及延迟增强在评估冠心病心肌缺血/存活中的局限性以及对比剂费用及相关安全性问题，本研究课题在前期工作的基础上，将非对比剂增强的T1 mapping技术与扩血管药物负荷相结合，并与传统方法（对比剂增强药物负荷心肌灌注及延迟增强）进行对比研究。通过随机动物实验研究设计，对非对比剂增强药物负荷T1 mapping成像在缺血性心脏病中的价值进行深入研究。项目预期将明确缺血性心脏病不同病变心肌（缺血心肌、冬眠心肌、梗死心肌）与正常心肌在静息及药物负荷下的T1阈值及变化率，进一步明确心肌T1值与心脏结构、功能关系及内在机制，初步了解缺血性心脏病不同病变心肌的演变情况。项目的研究成果对于缺血性心脏病诊断、治疗方案的临床决策，特别是针对左室重构，危险因素分层及预后判断具有重要意义，并可为相关基础与临床研究，特别是对左室重构机制、心肌细胞外间质及靶向药物治疗提供科学依据。

根据项目任务书中的研究计划，课题组现已按照实验流程完成了全部动物实验，包括心肌缺血模型的制作: 在第一对角支发出后在前降支放置3.0mm非金属环缩环，成功建立了心肌缺血动物实验模型。目前已成功造模48只动物（对照组6只，实验组42只），仅有1只动物在术后6天猝死，其余41只动物术后状态良好，全部存活。我们为所有动物在不同时间点进行了冠脉造影检查及磁共振检查，磁共振图像后处理及病理标本制作、染色。. 本研究实现了非对比剂增强药物负荷 T1 mapping成像并获得了缺血性心脏病不同性质心肌（缺血心肌、冬眠心肌、梗死心肌、正常心肌）的T1值及其变化阈值，进一步获得了细胞外间质容积（ECV）在上述不同心肌的阈值范围，并明确其与心肌收缩与舒张功能之间的关系。另外本研究以病理为金标准，明确了不同磁共振技术（非对比剂增强药物负荷 T1 mapping成像、对比剂增强药物负荷心肌灌注成像、对比剂延迟成像）在缺血性心脏病诊断与鉴别诊断中的价值。. 本课题开创性地将药物负荷与T1 mapping技术结合，首次通过动物实验，以病理为金标准，确定缺血性心脏病各种心肌（缺血心肌、冬眠心肌、梗死心肌、正常心肌）在静息及药物负荷下的组织特异性指标（T1值，ECV值）的正常阈值及动态变化情况，验证了非对比剂增强T1 mapping评估缺血性心脏病的可行性。我们的研究对磁共振缺血性心脏病扫描策略产生了革命性影响，大大缩短了扫描时间，同时节省了造影剂费用及避免造影剂相关安全问题，从而为临床早期干预提供方向，有利于阻止疾病进程，改善远期生存质量。