分数阶黏弹性和流性参量表征颈动脉粥样硬化斑块易损性的超声成像方法和实验研究

The rupture of carotid atherosclerotic plaque is important factor in leading to ischemic stroke and cardiovascular events. Thus, assessment of plaque vulnerability is of great significance for the prediction and early intervention of cardiovascular and cerebrovascular diseases. Studies have shown that the process of plaque formation and development involves molecular structure changes which lead to changes in tissue viscoelasticity and hemodynamic property. Existing imaging methods lack the ability to make accurate diagnosis for plaque vulnerability in vivo. Based on the preliminary studies on the viscoelasticity theory of plaque, fractional derivative model was proposed to describe the mechanical behavior of the plaque. Correlation between the viscoelasticity of plaque both in macro- and micro- scale and the pathological characteristics of plaque were analyzed. The aim of the project is to discover the viscoelasticity biomarker of the vulnerability grade of the plaque and set up the assessment criterion. The main work includes (1)study the fractional derivative model for plaque and parameters imaging methodology (2) develop multi-mode ultrasound viscoelasticity imaging method and experimental technique (3) culture animal plaque model or collecting plaque from carotid dissection. Study the fractional biomarkers for plaque at different stage by associating viscoelasticity and fluidity property to pathological features (4) demonstrates the validity of the proposed approach through 3D printing plaque, ex-vivo and clinical carotid plaque. This project can provide novel and important imaging methodology for accurate assessment of the vulnerability grade of the plaque.

颈动脉粥样斑块破裂是导致缺血性脑卒中和心血管事件的重要因素。易损性评估对预测及防范心脑血管疾病具有重大意义。斑块形成发展中分子结构发生变化导致组织黏弹性和血流动力学特性变化，现有影像学方法难以对斑块易损性进行直接准确评估。项目以前期血管壁黏弹性研究为基础，提出斑块的分数阶黏弹性模型，并将宏观尺度斑块黏弹性及流性参量、微观尺度斑块组织力学特性与斑块组织病理学特性进行关联分析，发现并提出斑块易损风险的黏弹性和流性参量表征，建立易损性评估准则。主要研究(1)分数阶黏弹性和流性参量成像理论方法(2)发展多模态超声黏弹性成像实验技术(3)培养动物易损斑块模型和收集颈动脉剥脱术斑块，将原子力显微镜测试的黏弹性特性与病理特性关联，发现不同发展时期斑块病理特性的分数阶黏弹性参量表征(4)利用3D打印仿体斑块模型，离体斑块和临床颈动脉斑块成像进行验证。项目为颈动脉斑块易损性准确评估提供重要的影像学新方法。

颈动脉粥样斑块破裂是导致缺血性脑卒中和心血管事件的重要因素。易损性评估对预测及防范心脑血管疾病具有重大意义。斑块形成发展中分子结构发生变化导致组织黏弹性和血流动力学特性变化，现有影像学方法难以对斑块易损性进行直接准确评估。项目提出斑块的分数阶黏弹性模型，将宏观尺度斑块黏弹性及流性参量、微观尺度斑块组织力学特性与斑块组织病理学特性进行关联分析，发现并提出斑块易损风险的黏弹性和流性参量表征。主要研究(1)分数阶黏弹性和流性参量成像理论方法(2)发展多模态超声黏弹性成像实验技术(3)培养动物易损斑块模型和收集颈动脉剥脱术斑块, 将力学测试的黏弹性特性与病理特性关联，发现不同发展时期斑块病理特性的分数阶黏弹性参量表征(4)利用3D打印仿体斑块模型，离体斑块和临床颈动脉斑块成像进行验证。.重要结果:(1) 提出并建立了分数阶黏弹性和流性参量成像理论方法（2）研制了多模超声黏弹性成像实验系统：Doppler超声监测入口血流速度，利用斑块几何建模和Comsol有限元分析数值求解斑块表面血流速度场和压场分布；常规B超同步采集斑块自主搏动运动时的视频序列，提出改进的block matching和光流场算法实现精准估计应变；提出KVFD模型精准表征了血管壁和斑块的应力-应变场力学响应，并研制了深度强化学习多参数优化算法，实现了黏弹流全局解的逼近。（3）通过仿真实验验证了分数阶黏弹流成像实验系统和算法的有效性。（4）收集了人体颈动脉剥脱术斑块离体数据进行了纳米压痕仪力学测试，并与病理学结果进行关联分析，发现了弹性和流性是易损性的重要指标（5）利用研制的成像方法，对3D打印的斑块模型进行了蠕动泵实验，同时对在体超声颈动脉斑块利用项目提出的方法进行了分数阶黏弹性和流性参量成像，其黏弹流参量表征与临床其他易损指标具有较好的一致性。.关键数据及其科学意义:采集的多模临床颈动脉斑块数据是利用本项目研制的成像系统进行在体斑块易损性评估的关键数据，项目为斑块早期易损性提供重要的影像学依据。