本文選題：肝纖維化 + 聲輻射力彈性成像　； 參考：《浙江大學(xué)》2014年博士論文

【摘要】：肝纖維化是走向肝硬化,甚至是肝癌的必由之路。肝纖維化的早期診斷和治療具有非常重要的臨床意義,對(duì)于輕度或明顯肝纖維化患者,其有助于減輕、逆轉(zhuǎn)甚至治愈肝纖維化；而對(duì)于肝硬化患者,及早進(jìn)行抗纖維化治療可以減慢疾病發(fā)展的速度,延長(zhǎng)生命。目前,肝穿刺活檢是肝纖維化程度評(píng)估的“金標(biāo)準(zhǔn)”。但是,該方法的診斷準(zhǔn)確性容易受取樣容積和位置的影響,且其是有創(chuàng)的,反復(fù)檢測(cè)不易被患者接受。近年來,超聲彈性成像技術(shù)發(fā)展迅速,該方法能檢測(cè)反映軟組織力學(xué)屬性的信息,具有無創(chuàng)、容易重復(fù)檢測(cè)等優(yōu)點(diǎn)。超聲彈性成像技術(shù),如聲輻射力脈沖成像、瞬態(tài)彈性成像,已經(jīng)被應(yīng)用于肝纖維化的臨床研究,但這些技術(shù)在肝纖維化診斷準(zhǔn)確性方面還有待于提高。本文主要針對(duì)基于聲輻射力的超聲彈性成像在肝纖維化評(píng)估中的若干關(guān)鍵技術(shù)問題進(jìn)行研究。首先,以線彈線模型為假設(shè)前提,提出一種改進(jìn)隨機(jī)抽樣一致的剪切波群速度估計(jì)方法。仿真與實(shí)驗(yàn)結(jié)果證明,該方法可以排除用于剪切波速度擬合的可疑異常數(shù)據(jù)點(diǎn),提高剪切波的估計(jì)準(zhǔn)確性。然后,為提高肝纖維化診斷的準(zhǔn)確率,提出了以最大化ROC曲線下面積為準(zhǔn)則的多模態(tài)特征聯(lián)合的方法。在臨床研究中,分別運(yùn)用聲輻射力脈沖成像、瞬態(tài)彈性成像和APRI指數(shù)等方法對(duì)乙肝患者進(jìn)行檢測(cè)評(píng)估,并將剪切波脈沖成像、瞬態(tài)彈性成像和APRI指數(shù)等多模態(tài)特征聯(lián)合用于乙肝肝纖維化分期的診斷。研究表明,該多模態(tài)聯(lián)合特征方法可以提高肝纖維化分期診斷的準(zhǔn)確性。基于線彈性模型的彈性成像技術(shù)只考慮彈性信息,而軟組織本質(zhì)上具有粘彈性屬性,因此,本文還將剪切波頻散聲振動(dòng)成像技術(shù)應(yīng)用于肝纖維化分期的評(píng)估。通過搭建系統(tǒng)實(shí)驗(yàn)平臺(tái),構(gòu)造大鼠肝纖維化動(dòng)物模型,并進(jìn)行離體超聲實(shí)驗(yàn),將實(shí)驗(yàn)結(jié)果與動(dòng)態(tài)力學(xué)分析、組織病理學(xué)測(cè)量的結(jié)果進(jìn)行對(duì)比研究。除了Voigt模型之外,本文還引入了Maxwell和Zener粘彈性模型進(jìn)行對(duì)比分析。通過實(shí)驗(yàn)數(shù)據(jù)分析,得到如下結(jié)論：(1) Maxwell粘彈性模型不太適合表征肝纖維化大鼠肝臟；(2)當(dāng)運(yùn)用Voigt模型時(shí),相比剪切彈性,剪切粘性對(duì)肝纖維化分期診斷的作用不顯著；(3) Zener模型的剪切彈性參數(shù)μ2對(duì)肝纖維分期的作用不大,而其它參數(shù)與Voigt模型參數(shù)的作用相當(dāng)；(4)與動(dòng)態(tài)力學(xué)分析的測(cè)量結(jié)果相比,剪切波頻散聲振動(dòng)成像對(duì)粘彈性參數(shù)的估計(jì)結(jié)果更為準(zhǔn)確。高頻剪切波對(duì)粘性參數(shù)的準(zhǔn)確估計(jì)非常重要。為了提高高頻剪切波的檢測(cè)能力,并研究其對(duì)粘彈性參數(shù)估計(jì)的影響,本文還介紹了基于正交頻率脈沖激勵(lì)的超聲振動(dòng)計(jì)方法。該方法通過構(gòu)造具有特定頻譜特性的正交頻率波形,經(jīng)稀疏采樣之后激勵(lì)組織振動(dòng),可以增強(qiáng)剪切波的高頻分量。在離體實(shí)驗(yàn)中,以新鮮豬肝為研究對(duì)象,選擇二進(jìn)制編碼和兩種正交頻率編碼脈沖激勵(lì)組織振動(dòng),然后分別運(yùn)用激光振動(dòng)計(jì)和超聲對(duì)不同編碼激勵(lì)方式產(chǎn)生的剪切波進(jìn)行檢測(cè)。激光振動(dòng)計(jì)實(shí)驗(yàn)證明了該方法可以有效增強(qiáng)剪切波的高頻分量,而從超聲實(shí)驗(yàn)結(jié)果上看,與二進(jìn)制編碼激勵(lì)方式的結(jié)果相比,當(dāng)只用100至400 Hz剪切波速度擬合求解時(shí),三碼片與六碼片的正交頻率脈沖激勵(lì)所估計(jì)得到的剪切彈性和剪切粘性的相對(duì)偏差分別為2.3%和4.1%,13.6%和11.5%；而當(dāng)將所有頻率剪切波速度用于擬合求解時(shí),三碼片與六碼片的正交頻率脈沖激勵(lì)所估計(jì)得到的剪切彈性和剪切粘性的相對(duì)偏差分別為10.6%和3.5%,5.4%和11.8%。實(shí)驗(yàn)結(jié)果表明,正交頻率編碼激勵(lì)方式可以降低激勵(lì)峰值聲強(qiáng),并提高系統(tǒng)對(duì)高頻剪切波的檢測(cè)能力；另一方面,高頻剪切波對(duì)粘彈性估計(jì)值具有影響,但其影響方式還不確定,需要進(jìn)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.

【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R575.2;R445.1

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本文編號(hào)：1882664