斑块血流灌注时空异质性的高造影组织比超声造影成像

It is valuable for stroke prevention to analyze spatial-temporal heterogeneity of blood perfusion in atherosclerotic plaques. Contrast-enhanced ultrasound (CEUS) enables visualization of blood perfusion in plaques and provides an emerging technique for analyzing properties of plaques. Currently, the analysis of plaque properties using CEUS is mainly focused on qualitative analysis, which is highly subjective and only provides discrete quantities. Some methods for quantitative analysis have been proposed but are limited in accuratly evaluating the spatial-temporal heterogeneity due to a low contrast-to-tissue ratio (CTR) resulted from artifacts. In this study, we will combine imaging techniques with image processing algorithms and investigate the quantitative analysis of spatial-temporal heterogeneity in plaque perfusion based on the CEUS imaging with a high CTR. First, we will seek mechanisms of artifact generation and propose approaches for suppressing artifacts to elevate the CTR. We will then investigate the detection of intraplque neovasculature and the extraction of features for quantifying the spatial-temporal heterogeneity in perfusion of the intraplque neovasculature. At last, the proposed CEUS with a high CTR and the quantitative methods will be applied to clinical patients, and thus provide a novel means for quantitative analysis of the properties of blood perfusion in plaques. It will offer a new tool for elucidating mechanisms of plaque generation and progression, which will be helpful for stroke prevention. The study can also be extended to analysis of blood perfusion properties in other tissues or organs such as liver, kidney and tumor.

分析颈动脉斑块血流灌注的时空异质性对预防脑卒中具有重要意义。超声造影(CEUS)能显示斑块血流灌注状况，成为分析斑块特性的新手段。目前基于CEUS分析斑块特性时以定性分析为主，存在主观性强、结果为离散量等缺点，而新近出现的定量分析法则受制于图像伪影引起的低造影组织比(CTR)，无法准确全面地评价灌注的时空异质性。本课题融合CEUS成像与图像处理技术，在研究高CTR的CEUS成像方法基础上，定量分析斑块血流灌注的时空异质性。首先从伪影的产生机制与影响因素入手，研究伪影的抑制方法以提升CTR，接着探索斑块内新生血管的检测方法，继而提取量化参数准确表征新生血管血流灌注的时空异质性，最后将该成像与定量分析技术应用于评价临床病例的斑块特性，检验其临床应用价值。课题将为阐明斑块发生发展机制提供新思路，利于预防脑卒中。研究成果亦可推广至其它组织或器官(如肝、肾、肿瘤)的血流灌注特性分析，具有可延伸价值。

颈动脉粥样硬化斑块的易损性对于脑卒中的发生发展具有重要影响。利用超声造影(contrast-enhanced ultrasound, CEUS)成像来观测斑块血流灌注特性，是评价斑块易损性的新途径。借助CEUS分析斑块特性的主流方法是定性分析法，存在主观性强、结果为离散量等缺点，而定量分析法则受制于图像伪影引起的低造影组织比(contrast-to-tissue ratio, CTR)，无法准确全面地评价灌注的时空异质性。本项目主要研究了CEUS伪影的产生原因及抑制方法，建立了高CTR的CEUS仿真模型及仿体实验平台，基于此检测在体实验中颈动脉斑块内新生血管，从而构建了定量分析斑块血流灌注时空异质性的新方法并进行了临床性能评估。仿体实验表明，运用微泡小波变换结合特征空间相干因子法的高CTR CEUS成像技术其CTR相对于传统延迟求和平面波法提高10.1dB。临床在体实验表明，本项目提出的两种评价斑块内新生血管血流灌注特性的定量分析方法(即改进的时间强度曲线法及造影剂空间分布法)能有效评价斑块血流灌注的时空异质性，提取的时间与空间异质性参数均与人工评级显著性相关(P<0.01)，并与病理学微血管密度显著性相关(面积比R=0.854，增强强度R=0.767；P<0.01)；借助因子分析从10个定量参数中提炼出5个相互独立的因子，这些因子与微血管密度的 R值高达0.932 (P = 0.006)。项目成果有望为无创检测易损斑块提供新工具，为阐明斑块发生发展机制提供新思路，为无创监测斑块的药物干预与治疗过程奠定基础，对预防中风具有重要意义。研究成果亦可推广至其它组织或器官(如淋巴结、肝、肿瘤)的灌注特性定量评价，具有可扩展的临床应用价值。