联合能谱CT心肌负荷灌注成像和冠脉TAG定量评价FFR和IMR以探讨冠脉狭窄与心肌缺血关系及病理生理机制的研究

Coronary artery disease (CAD) has become the most important disease that threatens people's health. The correlation between the severity of epicardial coronary stenosis and corresponding myocardial ischemia is poor. Therapeutic strategy decision only based on anatomical stenosis will easily cause stent abusement and other problems. Therefore, the latest PCI guidelines suggested to measure cardiac hemodynamic indices in order to accurately evaluate myocardial ischemia for the therapeutic strategy. However, a widespread implementation of the routine hemodynamic index measurement techniques has been hampered by several factors including its complexity, invasiveness, and expense. "How to measure the hemodynamic indices accurately and non-invasively?" and "how to understand the relationship between the coronary stenosis and myocardial ischemia?" have become the hot topics. Our previous studies validated that "fractional flow reserve (FFR)" and "index of microvascular resistance(IMR)" can be measured by using the angiography images based on the "first-pass distribution" perfusion principle. On this basis, the proposed study plans to quantify FFR and IMR by using myocardial stress perfusion imaging and coronary "transluminal attenuation gradient (TAG)" measurement on spectral CT in a swine animal model. The purpose of this study is to research the hemodynamic basis as well as the pathophysiological mechanism between the coronary stenosis and myocardial ischemia by synthesizing the cardiac hemodynamic, anatomical and pathological information. The significance of this study is to clarify the pathophysiological mechanism of the relationship between the anatomical coronary stenosis and physiological myocardial ischemia based on cardiac hemodynamic evaluation using non-invasive CT; to provide the reliable evidences for CAD early diagnosis, optimal treatment, and prognosis evaluation.

冠状动脉狭窄程度与其供血心肌缺血的严重程度之间的对应性较差，单纯根据解剖狭窄指导治疗易导致支架滥用。最新PCI指南建议行血液动力学检测来评估心肌缺血以辅助制定治疗策略，但常规测量方法侵入性高。如何无创、准确的评估心肌缺血，理解冠脉狭窄与心肌缺血之间的关系，成为当前热点问题。本课题组前期验证了基于"首过灌注"使用血管造影图像计算"冠状动脉血流储备分数(FFR)"和"微循环阻力指数(IMR)"的可行性。本研究在此基础上拟利用猪模型联合能谱CT心肌负荷灌注成像和冠状动脉CTA的"管腔内密度衰减梯度(TAG)"分析技术，通过定量FFR和IMR对心脏进行血液动力学评估，并综合解剖学、病理学等相关指标，探讨冠脉狭窄与心肌缺血关系的血液动力学基础及病理生理机制。本研究的意义在于，通过无创心脏血液动力学评估，阐明冠脉狭窄与心肌缺血关系的病理生理学基础，为冠心病的早期诊断、合理治疗及评判预后提供依据。

冠心病防治目的是"防心梗、防猝死"，冠状动脉狭窄程度与其供血心肌缺血的严重程度之间的对应性较差，单纯根据解剖狭窄指导治疗易导致支架滥用。最新PCI指南建议行血液动力学检测来评估心肌缺血以辅助制定治疗策略。如何无创且准确的评估心肌缺血、评估不同类型损伤心肌的血流动力学状况治疗冠心病的重中之重。本项目分别通过（1）14例猪闭胸模型（包含心外膜冠状动脉狭窄和微循环障碍模型）主要用于计算FFR和CFR来判断罪犯分支血管；（2）15例猪开胸模型为方便置入血流超声探头和血管外封堵器以提供血流量的参考标准，主要用于计算微循环阻力指数（IMR）的评估冠状动脉微循环系统状态；（3）12例猪闭胸急性心梗再灌注模型，主要用于与多模态方法相比较（包括SPECT、TTC染色、TUNEL染色）来评价心肌梗死。这些研究发现：（1）使用影像学方法计算血流动力学指标（FFR和CFR）可发现直径≥0.7mm 小血管的血流动力学异常，以辅助临床判断罪犯分支血管以明确诊断和治疗策略。（2）基于图像计算的标准化冠状动脉微循环阻力指数（NMR）可以为冠状动脉微循环提供较准确地评估，且独立于心外膜冠状动脉轻中度狭窄。（3）宝石能谱CTCA（延迟5min图像）识别梗死心肌节段与SPECT心肌灌注、TTC染色的一致性好。（4）无-复流区、心肌梗死区及远处正常心肌可通过能谱CT碘定量及免疫荧光TUNEL染色进行区别，心肌的能谱CTCA碘定量及心肌细胞凋亡计数呈显著负相关。（5）不同的 keV 水平对 TAG 值有一定的影响，且左、右冠状动脉的 TAG 值有显著差异。（6）基于HDTV正则化的去卷积方法能有效抑制心肌血流动力学参数图噪声和伪影，且实验结果更加逼近XCAT 真值参数图和高剂量参数图，且可以从MBF，MBV和MTT参数图判断出缺血心肌的范围。这些研究结果表明，使用无创影像学方法建立心脏血液动力学评估，并结合解剖学、病理学等相关指标，有助于明确冠状动脉狭窄与心肌缺血关系的血液动力学基础及病理生理机制，为冠心病的早期诊断、合理治疗及评判预后提供可靠依据。