基于声辐力的超声弹性成像关键技术及对肝纤维化评估的初步研究

发布时间：2018-05-13 09:52

本文选题：肝纤维化 + 声辐射力弹性成像　；参考：《浙江大学》2014年博士论文

【摘要】：肝纤维化是走向肝硬化,甚至是肝癌的必由之路。肝纤维化的早期诊断和治疗具有非常重要的临床意义,对于轻度或明显肝纤维化患者,其有助于减轻、逆转甚至治愈肝纤维化；而对于肝硬化患者,及早进行抗纤维化治疗可以减慢疾病发展的速度,延长生命。目前,肝穿刺活检是肝纤维化程度评估的“金标准”。但是,该方法的诊断准确性容易受取样容积和位置的影响,且其是有创的,反复检测不易被患者接受。近年来,超声弹性成像技术发展迅速,该方法能检测反映软组织力学属性的信息,具有无创、容易重复检测等优点。超声弹性成像技术,如声辐射力脉冲成像、瞬态弹性成像,已经被应用于肝纤维化的临床研究,但这些技术在肝纤维化诊断准确性方面还有待于提高。本文主要针对基于声辐射力的超声弹性成像在肝纤维化评估中的若干关键技术问题进行研究。首先,以线弹线模型为假设前提,提出一种改进随机抽样一致的剪切波群速度估计方法。仿真与实验结果证明,该方法可以排除用于剪切波速度拟合的可疑异常数据点,提高剪切波的估计准确性。然后,为提高肝纤维化诊断的准确率,提出了以最大化ROC曲线下面积为准则的多模态特征联合的方法。在临床研究中,分别运用声辐射力脉冲成像、瞬态弹性成像和APRI指数等方法对乙肝患者进行检测评估,并将剪切波脉冲成像、瞬态弹性成像和APRI指数等多模态特征联合用于乙肝肝纤维化分期的诊断。研究表明,该多模态联合特征方法可以提高肝纤维化分期诊断的准确性。基于线弹性模型的弹性成像技术只考虑弹性信息,而软组织本质上具有粘弹性属性,因此,本文还将剪切波频散声振动成像技术应用于肝纤维化分期的评估。通过搭建系统实验平台,构造大鼠肝纤维化动物模型,并进行离体超声实验,将实验结果与动态力学分析、组织病理学测量的结果进行对比研究。除了Voigt模型之外,本文还引入了Maxwell和Zener粘弹性模型进行对比分析。通过实验数据分析,得到如下结论：(1) Maxwell粘弹性模型不太适合表征肝纤维化大鼠肝脏；(2)当运用Voigt模型时,相比剪切弹性,剪切粘性对肝纤维化分期诊断的作用不显著；(3) Zener模型的剪切弹性参数μ2对肝纤维分期的作用不大,而其它参数与Voigt模型参数的作用相当；(4)与动态力学分析的测量结果相比,剪切波频散声振动成像对粘弹性参数的估计结果更为准确。高频剪切波对粘性参数的准确估计非常重要。为了提高高频剪切波的检测能力,并研究其对粘弹性参数估计的影响,本文还介绍了基于正交频率脉冲激励的超声振动计方法。该方法通过构造具有特定频谱特性的正交频率波形,经稀疏采样之后激励组织振动,可以增强剪切波的高频分量。在离体实验中,以新鲜猪肝为研究对象,选择二进制编码和两种正交频率编码脉冲激励组织振动,然后分别运用激光振动计和超声对不同编码激励方式产生的剪切波进行检测。激光振动计实验证明了该方法可以有效增强剪切波的高频分量,而从超声实验结果上看,与二进制编码激励方式的结果相比,当只用100至400 Hz剪切波速度拟合求解时,三码片与六码片的正交频率脉冲激励所估计得到的剪切弹性和剪切粘性的相对偏差分别为2.3%和4.1%,13.6%和11.5%；而当将所有频率剪切波速度用于拟合求解时,三码片与六码片的正交频率脉冲激励所估计得到的剪切弹性和剪切粘性的相对偏差分别为10.6%和3.5%,5.4%和11.8%。实验结果表明,正交频率编码激励方式可以降低激励峰值声强,并提高系统对高频剪切波的检测能力；另一方面,高频剪切波对粘弹性估计值具有影响,但其影响方式还不确定,需要进一步研究。
[Abstract]:Liver fibrosis is the only way to liver cirrhosis and even liver cancer. Early diagnosis and treatment of liver fibrosis have very important clinical significance. For patients with mild or obvious liver fibrosis, it helps to reduce, reverse and even cure liver fibrosis; for patients with liver cirrhosis, early anti fibrosis treatment can slow down the disease. The speed of development and prolongation of life. At present, liver biopsy is the "gold standard" for the evaluation of the degree of liver fibrosis. However, the diagnostic accuracy of this method is easily influenced by the volume and position of the sampling, and it is invasive, repeated detection is not easy to be accepted by the patient. In recent years, the technique of ultrasound elastography has developed rapidly, and this method can detect the reflection of the soft. Ultrasonic elastography, such as acoustic radiation force pulse imaging, transient elastic imaging, has been applied to the clinical study of liver fibrosis, but these techniques are still to be improved in the diagnosis of liver fibrosis. A number of key technical problems in the evaluation of liver fibrosis are studied by acoustic elastography. First, a linear elastic line model is used as the premise to improve the velocity estimation of shear wave group with random sampling. The simulation and experimental results show that this method can eliminate the suspicious abnormal data points for the shear wave velocity fitting. In order to improve the accuracy of the diagnosis of the liver fibrosis, to improve the accuracy of the diagnosis of liver fibrosis, a multi modal combination method is proposed, which maximizes the area under the ROC curve. In the clinical study, the acoustic radiation force pulse imaging, the transient elastic imaging and the APRI index are used to evaluate the patients with hepatitis B, and the shear will be cut. The multimodal features such as wave pulse imaging, transient elastography and APRI index are combined for the diagnosis of HBV staging. The study shows that the multimodal combined characteristic method can improve the accuracy of the diagnosis of liver fibrosis. Elastic imaging based on linear elastic model only takes care of the elastic information, while the soft tissue is essentially sticky. In this paper, the shear wave dispersion acoustic vibration imaging technology is also applied to the evaluation of liver fibrosis stages. By building a system experimental platform, the rat model of liver fibrosis is constructed and the experimental ultrasound experiments are carried out. The experimental results are compared with the dynamic mechanical analysis and the results of the histopathology measurement of the group Voigt. Besides the model, the Maxwell and Zener viscoelastic models were also introduced and analyzed. Through the experimental data analysis, the following conclusions were obtained: (1) the Maxwell viscoelastic model was not very suitable for the characterization of liver fibrosis rat liver; (2) when the Voigt model was used, the effect of shear viscosity on the diagnosis of liver fibrosis was not significant compared with shear elasticity. (3) the shear elastic parameters of the Zener model have little effect on the staging of liver fibers, and the other parameters are equivalent to the parameters of the Voigt model. (4) the estimation of the viscoelastic parameters by the shear wave dispersion acoustic vibration imaging is more accurate than that of the dynamic mechanical analysis. The accurate estimation of the viscosity parameters by the high frequency shear wave is the exact estimation of the viscoelastic parameters. It is very important. In order to improve the detection ability of high frequency shear wave and study its influence on the estimation of viscoelastic parameters, this paper also introduces an ultrasonic vibrormeter based on the orthogonal frequency pulse excitation. By constructing the orthogonal frequency waveform with specific spectrum characteristics, the method can stimulate the tissue vibration after sparse sampling and can enhance the shear. The high frequency component of the shear wave. In the experiment, the fresh pig liver was used as the research object. The vibration of the tissue was excited by binary encoding and two orthogonal frequency coding pulses. Then the shear wave produced by different coding excitation modes was detected by the laser vibrometer and ultrasonic. The excitation vibrometer experiment proved that the method could be effectively increased. The high frequency components of the strong shear wave are compared with the results of the ultrasonic experimental results. When compared with the results of the binary coded excitation method, the relative deviations of the shear elasticity and shear viscoelasticity estimated by the orthogonal frequency pulse excitation of the three and the six code slices are 2.3% and 4.1%, 13.6% and 11.5% respectively when compared with the results of the 100 to 400 Hz shear wave velocity fitting. When all the frequency shear wave velocities are used for fitting, the relative deviations of the shear elasticity and shear viscosity estimated by the orthogonal frequency pulse excitation of the three and the six code are 10.6% and 3.5% respectively. The experimental results of 5.4% and 11.8%. show that the orthogonal frequency coded excitation method can reduce the peak intensity of the excitation and improve the system. On the other hand, the high frequency shear wave has an influence on the viscoelastic estimation, but the way of its influence is still uncertain and needs further study.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R575.2;R445.1

【参考文献】