Yanrong Guo

The Role of Viscosity Estimation for Oil-in-gelatin Phantom in Shear Wave Based Ultrasound Elastography

Shear wave based ultrasound elastography utilizes mechanical excitation or acoustic radiation force to induce shear waves in deep tissue. The tissue response is monitored to obtain elasticity information about the tissue. During the past two decades, tissue elasticity has been extensively studied and has been used in clinical disease diagnosis. However, biological soft tissues are viscoelastic in nature. Therefore, they should be simultaneously characterized in terms of elasticity and viscosity. In this study, two shear wave-based elasticity imaging methods, shear wave dispersion ultrasound vibrometry (SDUV) and acoustic radiation force impulsive (ARFI) imaging, were compared. The discrepancy between the measurements obtained by the two methods was analyzed, and the role of viscosity was investigated. To this end, four types of gelatin phantoms containing 0%, 20%, 30% and 40% castor oil were fabricated to mimic different viscosities of soft tissue. For the SDUV method, the shear elasticity μ1 was 3.90 ± 0.27 kPa, 4.49 ± 0.16 kPa, 2.41 ± 0.33 kPa and 1.31 ± 0.09 kPa; and the shear viscosity μ2 was 1.82 ± 0.31 Pa•s, 2.41 ± 0.35 Pa•s, 2.65 ± 0.13 Pa•s and 2.89 ± 0.14 Pa•s for 0%, 20%, 30% and 40% oil, respectively in both cases. For the ARFI measurements, the shear elasticity μ was 7.30 ± 0.20 kPa, 8.20 ± 0.31 kPa, 7.42 ± 0.21 kPa and 5.90 ± 0.36 kPa for 0%, 20%, 30% and 40% oil, respectively. The SDUV results demonstrated that the elasticity first increased from 0% to 20% oil and then decreased for the 30% and 40% oil. The viscosity decreased consistently as the concentration of castor oil increased from 0% to 40%. The elasticity measured by ARFI showed the same trend as that of the SDUV but exceeded the results measured by SDUV. To clearly validate the impact of viscosity on the elasticity estimation, an independent measurement of the elasticity and viscosity by dynamic mechanical analysis (DMA) was conducted on these four types of gelatin phantoms and then compared with SDUV and ARFI results. The shear elasticities obtained by DMA (3.44 ± 0.31 kPa, 4.29 ± 0.13 kPa, 2.05 ± 0.29 kPa and 1.06 ± 0.18 kPa for 0%, 20%, 30% and 40% oil, respectively) were lower than those by SDUV, whereas the shear viscosities obtained by DMA (2.52 ± 0.32 Pa·s, 3.18 ± 0.12 Pa·s, 3.98 ± 0.19 Pa·s and 4.90 ± 0.20 Pa·s for 0%, 20%, 30% and 40% oil, respectively) were greater than those obtained by SDUV. However, the DMA results showed that the trend in the elasticity and viscosity data was the same as that obtained from the SDUV and ARFI. The SDUV results demonstrated that adding castor oil changed the viscoelastic properties of the phantoms and resulted in increased dispersion of the shear waves. Viscosity can provide important and independent information about the inner state of the phantoms, in addition to the elasticity. Because the ARFI method ignores the dispersion of the shear waves, namely viscosity, it may bias the estimation of the true elasticity. This study sheds further light on the significance of the viscosity measurements in shear wave based elasticity imaging methods.

Quantitative analysis of liver fibrosis in rats with shearwave dispersion ultrasound vibrometry: Comparison with dynamic mechanical analysis

Ultrasonic elastography, a non-invasive technique for assessing the elasticity properties of tissues, has shown promising results for disease diagnosis. However, biological soft tissues are viscoelastic in nature. Shearwave dispersion ultrasound vibrometry (SDUV) can simultaneously measure the elasticity and viscosity of tissue using shear wave propagation speeds at different frequencies. In this paper, the viscoelasticity of rat livers was measured quantitatively by SDUV for normal (stage F0) and fibrotic livers (stage F2). Meanwhile, an independent validation study was presented in which SDUV results were compared with those derived from dynamic mechanical analysis (DMA), which is the only mechanical test that simultaneously assesses the viscoelastic properties of tissue. Shear wave speeds were measured at frequencies of 100, 200, 300 and 400 Hz with SDUV and the storage moduli and loss moduli were measured at the frequency range of 1-40 Hz with DMA. The Voigt viscoelastic model was used in the two methods. The mean elasticity and viscosity obtained by SDUV ranged from 0.84±0.13 kPa (F0) to 1.85±0.30 kPa (F2) and from 1.12±0.11 Pa s (F0) to 1.70±0.31 Pa s (F2), respectively. The mean elasticity and viscosity derived from DMA ranged from 0.62±0.09 kPa (F0) to 1.70±0.84 kPa (F2) and from 3.38±0.32 Pa s (F0) to 4.63±1.30 Pa s (F2), respectively. Both SDUV and DMA demonstrated that the elasticity of rat livers increased from stage F0 to F2, a finding which was consistent with previous literature. However, the elasticity measurements obtained by SDUV had smaller differences than those obtained by DMA, whereas the viscosities obtained by the two methods were obviously different. We suggest that the difference could be related to factors such as tissue microstructure, the frequency range, sample size and the rheological model employed. For future work we propose some improvements in the comparative tests between SDUV and DMA, such as enlarging the harmonic frequency range of the shear wave to highlight the role of viscosity, finding an appropriate rheological model to improve the accuracy of tissue viscoelasticity estimations.

Measurement of Quantitative Viscoelasticity of Bovine Corneas Based on Lamb Wave Dispersion Properties

The viscoelastic properties of the human cornea can provide valuable information for clinical applications such as the early detection of corneal diseases, better management of corneal surgery and treatment and more accurate measurement of intra-ocular pressure. However, few techniques are capable of quantitatively and non-destructively assessing corneal biomechanics in vivo. The cornea can be regarded as a thin plate in which the vibration induced by an external vibrator propagates as a Lamb wave, the properties of which depend on the thickness and biomechanics of the tissue. In this study, pulses of ultrasound radiation force with a repetition frequency of 100 or 200 Hz were applied to the apex of corneas, and the linear-array transducer of a SonixRP system was used to track the tissue motion in the radial direction. Shear elasticity and viscosity were estimated from the phase velocities of the A0 Lamb waves. To assess the effectiveness of the method, some of the corneas were subjected to collagen cross-linking treatment, and the changes in mechanical properties were validated with a tensile test. The results indicated that the shear modulus was 137 ± 37 kPa and the shear viscosity was 3.01 ± 2.45 mPa · s for the group of untreated corneas and 1145 ± 267 kPa and was 0.16 ± 0.11 mPa · s for the treated group, respectively, implying a significant increase in elasticity and a significant decrease in viscosity after collagen cross-linking treatment. This result is in agreement with the results of the mechanical tensile test and with reports in the literature. This initial investigation illustrated the ability of this ultrasound-based method, which uses the velocity dispersion of low-frequency A0 Lamb waves, to quantitatively assess both the elasticity and viscosity of corneas. Future studies could discover ways to optimize this system and to determine the feasibility of using this method in clinical situations.

Ex vivo study of acoustic radiation force impulse imaging elastography for evaluation of rat liver with steatosis

HighlightsThe research by ARFI technology is focused on steatosis without fibrosis.ARFI elastography offers good diagnostic accuracy in evaluating the normal rat liver and rat liver with steatosis.The SWV measurements have no significant difference between the grades of steatosis.The early grade of inflammation activity does not significantly affect the SWV measurements. &NA; Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in developed countries. Accurate, noninvasive tests for diagnosing NAFLD are urgently needed. The goals of this study were to evaluate the utility of acoustic radiation force impulse (ARFI) elastography for determining the severity grade of steatosis in rat livers, and to investigate the changes in various histologic and biochemical characteristics. Steatosis was induced in the livers of 57 rats by gavage feeding of a high fat emulsion; 12 rats received a standard diet only and served as controls. Liver mechanics were measured ex vivo using shear wave velocity (SWV) induced by acoustic radiation force. The measured mean values of liver SWV ranged from 1.33 to 3.85 m/s for different grades of steatosis. The area under the receiver operative characteristic curve (≥S1) was equal to 0.82 (95% CI = 0.69, 0.96) between the steatosis group and the normal group, and the optimal cutoff value was 2.59 with sensitivity of 88% and specificity of 76%. However, there are no significant differences in SWV measurements between the steatosis grades. SWV values did not correlate with the early grade of inflammation. In conclusion, ARFI elastography is a promising method for differentiating normal rat liver from rat liver with steatosis, but it cannot reliably predict the grade of steatosis in rat livers. The early grade of inflammation activity did not significantly affect the SWV measurements.

Analyzing and modeling rheological behavior of liver fibrosis in rats using shear viscoelastic moduli.

The process of liver fibrosis changes the rheological properties of liver tissue. This study characterizes and compares liver fibrosis stages from F0 to F4 in rats in terms of shear viscoelastic moduli. Here two viscoelastic models, the Zener model and Voigt model, were applied to experimental data of rheometer tests and then values of elasticity and viscosity were estimated for each fibrosis stage. The results demonstrate that moderate fibrosis (≤F2) has a good correlation with liver viscoelasticity. The mean Zener elasticity E1 increases from (0.452±0.094) kPa (F0) to (1.311±0.717) kPa (F2), while the mean Voigt elasticity E increases from (0.618±0.089) kPa (F0) to (1.701±0.844) kPa (F2). The mean Zener viscosity increases from (3.499±0.186) Pa·s (F0) to (4.947±1.811) Pa·s (F2) and the mean Voigt viscosity increases from (3.379±0.316) Pa·s (F0) to (4.625±1.296) Pa·s (F2). Compared with viscosity, the elasticity shows smaller variations at stages F1 and F2 no matter what viscoelastic model is used. Therefore, the estimated elasticity is more effective than viscosity for differentiating the fibrosis stages from F0 to F2.概要研究目的肝脏的纤维化进程改变肝脏组织的流变属性。创新要点本文利用剪切黏弹性模量描绘并比较了大鼠肝脏F0 期到F4 期的纤维化过程。研究方法两个黏弹性模型, 即Zener 模型和Voigt 模型用于解释流变力学测试得到的实验数据, 由此得到每个纤维化分期的肝脏弹性和黏性值。重要结论肝脏中度纤维化(≤F2 期)与黏弹性值密切相关。 Zener 模型的弹性均值E1 从F0 期的 (0.452±0.094) kPa 增加到F2 期的(1.311±0.717) kPa, 而Voigt 模型的弹性均值E 从F0 期的 (0.618±0.089) kPa 增加到 F2 期的(1.701±0.844) kPa。 Zener 模型的黏性均值从F0 期的 (3.499±0.186) Pa·s 增加到F2 期的(4.947±1.811) Pa·s, 而Voigt 模型的黏性均值从F0 期的 (3.379±0.316) Pa·s 增加到F2 期的(4.625±1.296) Pa·s。 无论选用哪个黏弹性模型, 在F1 期和 F2 期, 肝脏弹性值的标准差比黏性值的标准差变化要小。 因此, 测得的弹性比黏性更有效地区分肝纤维化F0 期到F2 期。

Development of a Simple Noninvasive Model to Predict Significant Fibrosis in Patients with Chronic Hepatitis B: Combination of Ultrasound Elastography, Serum Biomarkers, and Individual Characteristics

OBJECTIVES: The accurate assessment of liver fibrosis is clinically important in patients with chronic hepatitis B (CHB). Blood tests and elastography are now widely used for the noninvasive diagnosis of liver fibrosis in CHB patients. The aim of this study was to develop a new and more accurate predictive model, which combines elastography data, serum biomarkers, and individual characteristics, to discriminate between CHB patients with and without significant liver fibrosis. METHODS: Two noninvasive methods, specifically, an ultrasound elastography technique termed acoustic radiation force impulse imaging (ARFI) and a blood test, were used to assess a cohort of 345 patients (estimation group, 218 patients; validation group, 127 patients) with CHB. Multivariate logistic regression analysis revealed that ARFI, the aspartate aminotransferase (AST) to platelet ratio, and age were significantly associated with fibrosis. Based on these results, we constructed and validated a model for the diagnosis of significant hepatic fibrosis. RESULTS: The area under the receiver operating characteristic (ROC) curve was 0.921 for the estimation group and 0.929 for the validation group, significantly higher than those for ARFI (0.887, 0.893) and for the AST‐to‐platelet ratio index (APRI; 0.811, 0.859). Using an optimal cutoff of 3.05 in the validation group, all the indices of the proposed model, including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio, were better than those for ARFI or APRI. CONCLUSIONS: We developed a simple noninvasive model that used ultrasound elastography, routine serum biomarkers, and individual characteristics to accurately differentiate significant fibrosis in patients with CHB. Compared with elastography or the biomarker index alone, this model was significantly more accurate and robust.

Quantitative Shear Elasticity Assessment of Liver Fibrosis in Rat Model with Shear Wave Elastography Base on Acoustic Radiation Force

Shear wave elstography based on acoustic radiation force is used for quantitative assessment of liver fibrosis in a rat model. The results show that the mean shear elasticity increases with the stage of liver fibrosis. The range of mean shear elasticity for all liver fibrosis stages is 1.25-3.17 kPa. The 95% confidence intervals of mean shear elasticity are overlapping for F1, F2, F3 and F4 stage. The results of ANOVA suggest that shear elasticity has significance difference between F0, F1 stage and F2, F3, F4 stage (P<;0.02), while shear elasticity has no significance between F0 and F1 stage (P=0.128), between F2, F3 and F4 stage (P>0.23). The AUC values of ROC curve of shear elasticity at METAVIR score threshold are 0.98 (≥F1), 0.95 (≥F2), 0.83(≥F3) and 0.83 (≥F4) respectively. The results suggest that shear wave elastography base on acoustic radiation force can be used potentially for early diagnosis and study of liver fibrosis.

Ultrasound vibrometry using orthogonal- frequency-based vibration pulses

New vibration pulses are developed for shear wave generation in a tissue region with preferred spectral distributions for ultrasound vibrometry applications. The primary objective of this work is to increase the frequency range of detectable harmonics of the shear wave. The secondary objective is to reduce the required peak intensity of transmitted pulses that induce the vibrations and shear waves. Unlike the periodic binary vibration pulses, the new vibration pulses have multiple pulses in one fundamental period of the vibration. The pulses are generated from an orthogonal-frequency wave composed of several sinusoidal signals, the amplitudes of which increase with frequency to compensate for higher loss at higher frequency in tissues. The new method has been evaluated by studying the shear wave propagation in in vitro chicken and swine liver. The experimental results show that the new vibration pulses significantly increase tissue vibration with a reduced peak ultrasound intensity, compared with the binary vibration pulses.

Model-dependent and model-independent approaches for evaluating hepatic fibrosis in rat liver using shearwave dispersion ultrasound vibrometry

This study assesses gradations of hepatic fibrosis in rat livers using both model-dependent and model-independent approaches. Liver fibrosis was induced in 37 rats using carbon tetrachloride (CCl4); 6 rats served as the controls. Shear wave velocity as a function of frequency, referred to as velocity dispersion, was measured in vitro by an ultrasound elastography method called shearwave dispersion ultrasound vibrometry (SDUV). For the model-dependent approach, the velocity dispersion data were fit to the Voigt model to solve the viscoelastic modulus. For the model-independent approach, the pattern of the velocity dispersion data was analyzed by linear regression to extract the slope and intercept features. The parameters obtained by both approaches were evaluated separately using a receiver operating characteristic (ROC) curve analysis. The results show that, of all the parameters for differentiating between grade F0-F1 and grade F2-F4 fibrosis, the intercept had the greatest value for the area under the ROC curve. This finding suggests that the model-independent approach may provide an alternative method to the model-dependent approach for staging liver fibrosis.

Viscoelastic properties of normal rat liver measured by ultrasound elastography: Comparison with oscillatory rheometry.

BACKGROUND Ultrasound elastography has been widely used to measure liver stiffness. However, the accuracy of liver viscoelasticity obtained by ultrasound elastography has not been well established. OBJECTIVE To assess the accuracy of ultrasound elastography for measuring liver viscoelasticity and compare to conventional rheometry methods. In addition, to determine if combining these two methods could delineate the rheological behavior of liver over a wide range of frequencies. METHODS The phase velocities of shear waves were measured in livers over a frequency range from 100 to 400 Hz using the ultrasound elastography method of shearwave dispersion ultrasound vibrometry (SDUV), while the complex shear moduli were obtained by rheometry over a frequency range of 1 to 30 Hz. Three rheological models, Maxwell, Voigt, and Zener, were fit to the measured data obtained from the two separate methods and from the combination of the two methods. RESULTS The elasticity measured by SDUV was in good agreement with that of rheometry. However, the viscosity measured by SDUV was significantly different from that of rheometry. CONCLUSIONS The results indicate that the high frequency components of the dispersive data play a much more important role in determining the dispersive pattern or the viscous value than the low frequency components. It was found that the Maxwell model is not as appropriate as the Voigt and Zener models for describing the rheological behavior of liver.