基于DCE-MRI和生物力学对小型猪颅内外AS斑块内新生血管通透性和局部应力负荷的关联性研究

Atherosclerosis (AS) could trigger a series of acute cardiocerebrovascular events, which is a serious hazard to human health. The morphological characters of vulnerable plaques have been discovered to contain large lipid-rich necrotic core, intraplaque hemorrhage and thin fibrous cap, especially intraplaque hemorrhage is the critical factor that lead to plaque destabilization. Some study found that the high permeability and high mechanical load of intraplaque neovessels would be likely to promote intraplaque hemorrhage. Although the in vivo studies used high resolution magnetic resonance imaging (HR-MRI) to find that contrast enhancement of plaque is closely related with intraplaque neovascularization, the relationships between increased permeability of neovessels and changes of micro-mechano-environment remain unclear. By the use of dynamic contrast-enhanced MRI (DCE-MRI) and biomechanical method, this study will focus on the mechanical microenvironment around neovessels to carry out research on intracranial and extracranial arteries of minipig AS models as the following aspects: (1) to analysis the relationship between the quantitative parameters of DCE-MRI and density and permeability of neovessels; (2) to describe the mechanical load of intraplaque neovessels by the digital pathological image-based mechanical models; (3) to explore the relationships of neovessels’ permeability, inflammatory cell infiltration and local mechanical conditions. We hope this study could reveal the internal mechanism of the mechanically-induced fragility of neovasculature, which could increase the accuracy of the early prediction of vulnerable plaque rupture risk.

动脉粥样硬化症（AS）可引发一系列急性心脑血管事件，严重危害人类健康。易损斑块的形态特征有大的脂核、斑块内出血和薄的纤维帽，尤其是斑块内出血是导致斑块失稳的关键因素。研究发现斑块内新生血管的高通透性和高应力负荷可能促进了斑块内出血的形成。利用高分辨磁共振技术发现斑块的强化与斑块内新生血管密切相关，但是斑块内新生血管的通透性增加与力学微环境变化的关系尚不明确。本研究拟利用动态增强磁共振（DCE-MRI）技术结合生物力学方法，以斑块内新生血管周围应力微环境为切入点，对小型猪AS模型的颅内外血管开展三方面的研究：（1）阐明DCE-MRI定量参数与新生血管密度及通透性的关系；（2）基于数字化的病理图像构建力学模型，了解斑块内新生血管的应力负荷；（3）探讨新生血管通透性、炎症细胞浸润程度与局部应力微环境的关系。希望通过本项目了解新生血管脆性的力学机制，从生物力学角度早期鉴别易损斑块潜在的破裂风险。

动脉粥样硬化症（AS）是危害人类健康的常见病，可引发一系列致命性或致残性的急性心脑血管事件。已有研究证明缺血事件并不一定直接与血管狭窄程度相关，而是与斑块的成分、尤其是斑块内出血和炎症程度有关。AS炎症的组织学标志之一是新生血管形成，而新生血管在斑块的发生、发展及失稳中也扮演着重要角色。本项目利用动态增强磁共振（DCE-MRI）技术结合生物力学方法，以斑块内新生血管周围应力微环境为切入点，对动物AS模型的动脉开展了三方面的研究：（1）建立并优化了适用于动物的动脉高分辨磁共振管壁成像（MR-VWI）方案、包括DCE-MRI序列，验证了成像方案的可靠性和可重复性。本部分采用的MR-VWI优化方案提高了图像质量，为动物模型管壁形态学的定量研究奠定了基础；本研究采用的DANTE黑血预备的3D CUBE序列扫描范围较大、时间效率较高，且空间分辨率可达到对动脉粥样硬化血管进行定量评估的要求。（2）对动物的动脉粥样硬化血管进行了病理检查和病理图片的数字化处理，与DCE-MRI等管壁成像序列相对应分析，探索了DCE-MRI与新生血管密度及通透性的关系。本部分的研究所采用的3D DCE-MRI序列可以量化动脉粥样硬化血管管壁病变的新生血管生成，并一定程度反映微血管的通透性。（3）基于数字化的病理图片构建血管的力学模型，根据斑块内新生血管周围红细胞漏出情况，初步探讨了新生血管通透性与局部应力负荷的关系。本部分结果表明周围有红细胞的新生血管的局部峰值最大主应力（Stress-P1）较高，并承受了较大的主伸长比（Stretch-P1）变异，提示周围有红细胞的新生血管处于较为恶劣的局部机械环境中。由此，本项目探索了斑块内新生血管脆性的力学机制，从生物力学角度为鉴别易损斑块补充了新的手段。

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