基于分子影像技术探讨微钙化在动脉粥样斑块演变中的作用

Early noninvasive detection of vulnerable coronary artery plaques is significant for the prevention and treatment of acute cardiac events, but so far there is no ideal method. Based on the previous complished research on detection of vulnerable plaques using 18F- FDG PET/CT imaging, 18F - sodium fluoride, which is not absorbed by myocardium, as imaging agent,will be used to explore the process of microcalcification variation throughout the evolution of atherosclerotic plaques. Rabbit model of atherosclerosis is employed, and atorvastatin is used to stablize plaques. The rabbits undergo pharmacological triggering to induce plaque rupture. 18F - sodium fluoride PET is used to detect the microcalcification, and CT to evaluate the vascular stenosis, plaque morphology and thrombosis. Pathology, histochemistry, apoptosis detection and PCR analysis will be used to analyze the plaque composition, tissue calcification, inflammation and cell apoptosis. One hundred and twenty patients with coronary heart disease will be recruited, and vulnerable plaques are identified by OCT (Optical Coherence Tomography). 18Fsodium fluoride PET will be used to detect coronary artery microcalcification, and CT to evaluate luminal stenosis, plaque CT value, the positive remodeling of blood vessels and all patients will be followed up for two years. To investigate the changes of microcalcification and the characteristics of 18F-NaF imaging in different stages of atherosclerosis (stable, vulnerable, ruptured and thrombus),.we aim to elucidate the role of 18 F - sodium fluoride molecular imaging technique in detecting vulnerable plaques and the potential mechanism and propose the risk score and stratification method of coronary artery plaques, which can further to lay a foundation for early diagnosis of high risk patients with coronary heart disease.

冠状动脉易损斑块早期无创检测对急性心脏事件的防治有重要意义，但尚无理想方法。在完成 18F-FDG PET/CT检测易损斑块的基础上，采用不受心肌干扰的18F-NaF为显像剂，探讨动脉粥样斑块演变过程中微钙化的变化规律。选用兔动脉粥样硬化模型，阿托伐他汀干预斑块进展，药物激发诱发斑块破裂，18F-NaF PET检测微钙化，CT评价血管狭窄、斑块形态和血栓；病理、组化、凋亡检测和PCR分析斑块成分、组织钙化、炎症和细胞凋亡。120例冠心病患者为临床研究对象，OCT检测确定易损斑块，18F-NaF PET检测冠状动脉微钙化，CT评价管腔狭窄、斑块CT值、钙化和血管重构，随访2年。探讨动脉硬化不同发展阶段（稳定、易损、破裂或血栓）微钙化的变化规律和18F-NaF成像特点，阐明18F-NaF分子影像技术检测易损斑块的作用，提出冠状动脉斑块危险积分和分层方法，为高危冠心病患者早期诊断奠定理论基础。

动脉粥样硬化是冠心病和缺血性脑卒中的主要病因，而斑块破裂和随之发生的急性血栓形成是导致急性冠脉事件和严重临床表现（急性心肌梗死、心源性猝死和缺血性卒中）的主要机制。易于破裂并导致血栓形成的斑块被称为易损斑块或高危斑块。斑块的易损性主要由斑块的内在特性和斑块的生物机械应力共同决定。病理学研究表明炎症和钙化是决定斑块进展和破裂的主要组成部分。组织学和影像学研究发现，微钙化通常与高危罪犯动脉粥样硬化斑块特征相联系。目前，传统的影像学方法对早期易损斑块的检测效果欠佳，因此寻找早期检测易损斑块的合适方法是目前心血管领域急需解决的问题。正电子发射计算机断层显像技术是一种功能和代谢显像方法，因其具有较高的敏感性、非侵入性、定量及功能检测的特点，已经被广泛应用于心血管疾病的研究领域。氟18-氟化钠（Fluoride18-Sodium fluoride, 18F-NaF）是一种PET示踪剂，可以通过物理和化学的方式吸附于钙化表面，提示其对易损斑块的识别可能有重要的价值。.因此，本研究以动脉粥样硬化兔模型为研究对象，将18F-氟化钠活体显像信息与病理、组化等资料进行相关性分析，揭示18F-NaF PET/CT活体显像对动脉粥样硬化斑块易损性的诊断价值。通过阿托伐他汀治疗干预斑块进展，分析阿托伐他汀对兔动脉粥样硬化斑块内炎症和微钙化的影响。