血管内超声对滋养血管新生靶向成像评价斑块稳定性

Vasa vasorum and neovascularization of atherosclerosis plaque are closely related to the progression and stability of plaque. The molecular imaging of angiogenesis would helps to identification of vulnerable plaques and predicting future cardiovascular events. We, recently, applied ultrasound molecular imaging for assessing the angiogenesis of ischemic lower limbs by neovascularization-targeted microbubbles,which targeted to αv-integrins, and successfully conduct contrast imaging with contrast microbubbles in vasa vasorum of rabbit aorta by intravascular ultrasound (IVUS), which aim to overcoming the hampers of insufficient specificity and spatial resolution of vasa vasorum and neovascularization molecular imaging of plaque. On this foundation, application of IVUS to imaging the neovascularization of plaque on miniature pig model are going to be conducted by ultrasound molecular probe targeted to αv-integrins which high express in neovascularization. Furthermore, We are going to compare the change of ultrasonic signal of molecular imaging and changes of the molecular level which closely related to inflammation as well as the pathological characteristic of plaque before and after using atorvastatin. In atherosclerotic miniature pig model, we are going to clarify the relation between ultrasound molecular signal and histopathological characteristic of atherosclerosis, and determine the role of IVUS molecular imaging of vasa vasorum and neovascularization on assessing of stability of plaque. This study would provide new insight into the vulnerable plaques and eventually lead to development of new repeatable, positionable, quantitative and visual approach to accessing the progression and stability of atherosclerosis plaque in vivo.

动脉粥样硬化斑块滋养血管新生与动脉粥样硬化斑块进展和稳定性密切相关，新生滋养血管成像有助于识别和预警易损斑块。针对新生滋养血管成像特异性低、空间分辨率不足的瓶颈问题，我们前期应用携αv-integrins单抗靶向超声微泡评价了缺血下肢血管新生的效果，利用血管内超声成功对兔主动脉滋养血管进行了普通造影剂微泡对比成像，在此基础上，拟采用在新生滋养血管中高表达的αv-integrins靶向超声分子探针，创新性的应用血管内超声在小型猪冠状动脉斑块模型上，对斑块新生滋养血管进行超声分子成像，并对比阿托伐他汀作用前后分子成像超声信号的变化，同时检测与斑块炎症状态密切相关的蛋白分子水平和斑块组织病理的变化，探讨利用超声血管新生分子探针信号特征评估斑块病理生理状态，为在体评价冠状动脉粥样硬化斑块进展和稳定性提供可重复进行，可定位、定量和可视化的新方法。

动脉粥样硬化斑块新生滋养血管与动脉粥样硬化斑块进展和稳定性密切相关，新生滋养血管成像有助于识别和预警易损斑块。针对新生血管成像特异性低、空间分辨率不足的瓶颈问题，我们通过制备靶向滋生滋养血管的cRGD(环状精氨酸-甘氨酸-天冬氨酸)微泡，应用血管内超声（IVUS）成功实现对斑块新生滋养血管进行在体成像，实现利用超声血管新生分子探针评估斑块病理生理状态，并进一步通过病理组织学进行验证了成像的可靠性，为在体评价冠状动脉粥样硬化斑块进展和稳定性提供了一种可重复进行，可定位、定量和可视化的新方法。