| Development of liver fibrosis will result in liver cirrhosis, even lead to liver cancer ultimately. Early diagnosis and treatment of liver fibrosis has very important clinical significance. For patients with mild or significant hepatic fibrosis, it will help to reduce, reverse or even cure liver fibrosis. For patients with liver cirrhosis, early anti-fibrotic therapy will help to slow down the progression of the disease and prolong life. Currently, liver biopsy is the "gold standard" for evaluating liver fibrosis. However, the diagnostic accuracy of this method may be affected by the sampling volume and positions. Moreover, this method is invasive and repetive measuremt is not easily accepted by the patients. In recent years, ultrasound-based elastography develop rapidly. This method can measure information representing mechanical properties of soft tissue and have the advantages of noninvasive and easy to measure repeatly. Ultrasound-based elastography techniques, such as acoustic radiation force imaging and transient elastography, were applied to clinical study of liver fibrosis staging. However, the diagnosis accuracy of liver fibrosis still needs to be improved.In this paper, we studied some key technologies in the assessment of liver fibrosis with ultrasound elastography based on acoustic radiation force. Firstly, assuming linear elasticity model, a modified randon sample consensus algorithm for estimation of shear wave group velocity was proposed. The results of simulations and experiments demonstrate that this method can exclude some suspicious abnormal data points used for shear wave velocity fitting calculation.and improve the accuracy of the shear wave velocity estimation. Then, to improve the diagnostic accucy of liver fibrosisi, a multi-modal features combination method which is in criterion of maximum the area under ROC curve, was proposed. In clinical studies, techniques of acoustic radiation force pulse image (ARFI), transient elastography (TE) and APRI were used for testing and evaluting patients with hepatitis B respectively. Liver fibrosis was also evaluated by a muti-modal feature combined by ARFI, TE and APRI. The results suggest that this method can improve the accuracy of diagnosis of liver fibrosis.Elastography method based on linear elastic model only consider the elasticity information, however, soft tissue essentially has viscoelastic properties. Therefore, a method of shear wave dispersion vibrometry was also used to evaluate staging of liver fibrosis in the paper. Experiment setup and animal model of liver fibrosis of rat was built, and then in vitro ultrasound experiment was conducted. The results of in vitro experiment were compared with that of dynamic mechanical analysis and histopathological measurements. Besides the Voigt viscoelastic model, Maxwell and Zener viscoelastic model were also introduced for comparision in this paper. Through experiment data analyzation, the following conclusions were obtained:(1) Maxwell viscoelatic model is not suitable for characterizing liver fibrosis of rat. (2) shear viscosity was not as significant as shear elasticity in staging liver fibrosis when using Voigt viscoelastic model. (3) parameter rμ2 of the Zener viscoelastic model has no significant effect of diagnosis of liver fibrosis, and the other parametrs are similar to parameters of the Voigt model (4) shear wave dispersion vibrometry can offer more accurate results of viscoelasticity estimation than dynamic mechanical analysis.High frequency shear wave is very important for accurately estimating values of viscosity. To improve the detecting ability of high frequency shear wave and investigate its impact on estimation of viscoelastic parameters, a method based on orthogonal frequency pulse excitation for ultrasound vibrometry was introduced in this paper. In this method, an orthogonal frequency wave with preferred spectrum distribution was designed and sampled sparsely and used to induce tissue vibration, which can enhance the energy of higher harmonic of induced shear wave. In vitro experiment, fresh swine liver was chosen as study object. Binary pulse and two orthogonal frequency pulses were chosen for inducing tissue vibration and the shear waves induced by different excitation pulses were detected by using laser vibrometry and ultrasound technique. Laser vibrometry experiment demonstrates that this method can enhance effectively the high frequency component of induced shear wave. As can be seen from the result of the ultrasound experiment, comparing with the results of binary pulse excitation, the relative bias of estimation of shear elasticity and shear viscosity were 2.3% and 4.1%,13.6% and 11.5% for three-chip and six-chip orthogonal pulse excitation respectively when using velocity of frequency of 100 to 400 Hz for fitting calculation. And the relative bias of estimation of shear elasticity and shear viscosity were 10.6% and 3.5%,5.4% and 11.8% for three-chip and six-chip orthogonal pulse excitation respectively when using velocity of all frequency for fitting calculation. Experiment results suggest that orthogonal frequency pulse excitation can reduce the peak ultrasound intensity and enhance the detecting ability of higher harmonic shear wave. On the other hand, the estimated values of viscoelasticity can be impacted by the higher harmonic shear wave, but its way of impact is still unknown and need further study. |