Po-Ling Kuo

ELASTIC MODULUS MEASUREMENTS OF HUMAN LIVER AND CORRELATION WITH PATHOLOGY

Viral hepatitis causes fibrosis in the liver and may change mechanical properties of the liver. To evaluate the impact of fibrosis on elastic properties of human liver and to investigate potential benefits of ultrasonic elasticity imaging, 19 fresh human liver samples and 1 hepatic tumor (focal nodular hyperplasia) sample obtained during operations were studied. Simple 1-D estimates based on the cyclic compression-relaxation method were performed. Elastic modulus values were derived from the predetermined strain (controlled by a step motor system) and the stress values (measured by an electronic balance). Each specimen subsequently received histologic examination and a grade of liver fibrosis was scored from 0 to 5. Results show that the elastic modulus values were on the order of several hundreds to thousands of Pascals. The elastic modulus generally increased with the fibrosis grade, although some discrepancies existed at the middle grades of fibrosis (scores 1 to 3). The correlation between the fibrosis score and the elastic modulus was significant (p < 0.01) based on the statistical analysis using the Pearson correlation method. In addition, the relation between the elastic modulus and the fibrosis grade generally exhibited a quadratic trend. It was concluded that severity of fibrosis had a good correlation with stiffness of the liver. Results also indicated that the elasticity imaging of the liver may provide significant clinical values if the elastic modulus can be accurately measured.

ELASTIC PROPERTIES OF TENDON MEASURED BY TWO DIFFERENT APPROACHES

Elastic properties of tendon were assessed by two different approaches. Six fresh bovine Achilles tendon specimens were used. The first approach directly measured Youngs modulus along the transverse direction (E(perpendicular)) and the longitudinal direction (E(parallel)), using a cyclic compression-relaxation method. Youngs moduli were derived based on the measured strain and stress values. The ratio of E(parallel): E(perpendicular) at smaller strains was around 4 and decreased to 0.6 approximately 1.1 at larger strains. The second approach assumed that tendons are transversely isotropic. Three observable second-order elastic stiffness constants (c(11), c(13) and c(33)) were obtained by sound speed measurements along various propagation directions. The measured elastic stiffness constants were also correlated with results from the first approach. It was shown that the transverse isotropy assumption was valid at small strains. However, a significant discrepancy existed between the two approaches. The discrepancy was primarily due to viscoelasticity associated with the first approach.

Young's modulus measurements of human liver and correlation with pathological findings

Viral hepatitis causes fibrosis in liver and may change livers mechanical properties. To evaluate the impact of fibrosis on elastic properties of human liver and to investigate potential benefits of ultrasonic elasticity imaging, nineteen fresh human liver samples and one hepatic tumor (focal nodular hyperplasia) sample obtained during operations were studied. Simple ID estimates based on the cyclic compression-relaxation method were preformed. Youngs modulus values were derived from the pre-determined strain (controlled by a step motor system) and the stress values (measured by an electronic balance). Each specimen subsequently received histological examination and a grade of liver fibrosis was scored from 0 to 5. Results show that the Youngs modulus values were at the order of several hundreds to thousands Pascals. The Youngs modulus generally increased with the fibrosis grade though some discrepancies existed at the middle grades of fibrosis (score 1-3). The correlation between the fibrosis score and the Youngs modulus was significant (P<0.01) based on the statistical analysis using the Pearson correlation method.

Investigation on anisotropy of elastic properties in tendon using shear wave elasticity imaging

Non-invasive evaluation of tendon structure and function is of great use clinically. We proposed that the shear wave elasticity imaging has a better potential in differentiating normal and destructed tendon tissue than high frequency sonography. Four in vitro porcine tendons were studied in this research. High frequency ultrasound could provide good spatial resolution to monitor the detail structure changes by collagenase alterations. By analyzing the speckle changes based on defining a signal to noise ratio (SNR), we could quantitatively estimate the structure differences. The SNR alteration in the region of interest (ROI) before and after collagenase injection is close to 4%. The changes induced by structure alterations are not obvious even through in high frequency ultrasound imaging. Further to analyze the changes of shear wave speed, the differences before and after collagenase injection in longitudinal and transverse section of tendon were 21.3% and 8.3%, respectively. From our results, we found the changes of shear wave speed were much more than speckle intensity alterations after collagenase injection. Moreover, the decrease ratio of shear wave speed in longitudinal section is much more than in transverse section. In other words, to diagnose the tendon disease could prior to investigate on the changes of mechanical property in longitudinal section of tendon. The changes of shear wave speed could provide a batter characteristic for differentiation of normal or diseased tissue.

Shear-wave elasticity measurements of three-dimensional cell cultures for mechanobiology.

ABSTRACT Studying mechanobiology in three-dimensional (3D) cell cultures better recapitulates cell behaviors in response to various types of mechanical stimuli in vivo. Stiffening of the extracellular matrix resulting from cell remodeling potentiates many pathological conditions, including advanced cancers. However, an effective tool for measuring the spatiotemporal changes in elastic properties of such 3D cell cultures without directly contacting the samples has not been reported previously. We describe an ultrasonic shear-wave-based platform for quantitatively evaluating the spatiotemporal dynamics of the elasticity of a matrix remodeled by cells cultured in 3D environments. We used this approach to measure the elasticity changes of 3D matrices grown with highly invasive lung cancer cells and cardiac myoblasts, and to delineate the principal mechanism underlying the stiffening of matrices remodeled by these cells. The described approach can be a useful tool in fields investigating and manipulating the mechanotransduction of cells in 3D contexts, and also has potential as a drug-screening platform. Summary: Use of a non-direct-contact platform for measurement of the spatiotemporal dynamics of matrix elasticity when remodeled by cells cultured in three-dimensional contexts.

Shear Wave Measurements for Evaluation of Tendon Diseases

This study investigated the feasibility of using supersonic shear wave measurements to quantitatively differentiate normal and damaged tendons based on their mechanical properties. Five freshly harvested porcine tendons excised from pig legs were used. Tendon damage was induced by incubating the tendons with a 1% w/v collagenase solution. Values of shear modulus were derived both by a time-of-flight (TOF) approach and by a transverse isotropic plate model (TI-model). Results show that as the preload applied to the tendon increased from 0 to 3 N, the mean shear modulus derived based on the TOF approach, the TI-model, and Youngs modulus estimated from mechanical testing increased from 14.6 to 89.9 kPa, 53.9 to 348 kPa, and from 1.45 to 10.36 MPa, respectively, in untreated tendons, and from 8.4 to 67 kPa, 28 to 258 kPa, and from 0.93 to 7.2 MPa in collagenase-treated tendons. Both the TOF approach and the TI-model correlated well with the changes in Youngs moduli. Although there is bias on estimation of shear modulus using the TOF approach, it still provides statistical significance to differentiate normal and damaged tendons. Our data indicate that the SSI is a valuable imaging technique to assess tendon stiffness dynamics and characterize normal and collagenase-damaged tendons.

Stiffness dynamics of rabbit's achilles tendons evaluated by shear wave elastography in vivo

The physiological function of tendon is to withstand the tension generated by muscles during various type of joint movement, and thus prevent muscle from violent damage. Hence, the dynamic change of tendon stiffness for adapting various external forces is highly related to its functional performance. In other words, monitoring the dynamic tendon stiffness at various stretching conditions can be used for assessment of tendon functions. Recently, a relatively new imaging technique called shear wave elastography (SWE) has emerged as a promising tool for estimation of tissue stiffness. However, because tendons are anisotropic materials with the highest stiffness along the longitudinal direction, the general relation between the shear wave speed and Youngs modulus derived from isotropic materials (i.e., E=3ρc2) does not hold. To precisely estimate the mechanical properties of tendon, it is necessary to analyze the velocity dispersion of the guided waves propagating inside tendons. The aim of this study is thus to evaluate SWE combined with dispersion analysis as a diagnostic tool for tendon functionality by monitoring the dynamics of tendon stiffness at various stretching conditions. SWE was in vivo applied to six Achilles tendons of three New Zealand rabbits. Assuming the tendons as a transverse isotropic material, the tendons were passively stretched at four ankle joint angles and the dispersion of shear waves running in parallel with the longitudinal direction of the tendons were analyzed to yield the elastic constants C55 in Christoffels tensor. The measured mean value of C55 at joint angles of 125°, 110°, 95° and 80°were 0.42MPa, 0.95MPa, 1.49MPa and 2.27MPa, respectively. Our results show that the change of C55 is highly correlated with the stretching conditions. This suggests that the dynamic stiffness of tendon at various stretching conditions can be monitored by elastic constant C55. In summary, SWE combined with dispersion analysis is a powerful tool to non-invasively monitor the stiffness dynamic changes of tendons and highly potential for diagnosis of tendon injury and monitoring of the treatment efficiency.

Correlation between the shear wave speed in tendon and its elasticity properties

Mechanical properties, such as the Youngs modulus, of the tendon are highly correlated to its pathological state. The isolated tensile testing is the conventional method for measuring the Youngs modulus of tendon. However, it is an invasive process and is not suitable for early diagnosis. A non-invasive method for measuring the Youngs modulus of tendon is thus highly desired. Recently, shear wave elasticity imaging has been widely used to quantify the elasticity property of soft tissue non-invasively. Up to date, the relation between the Youngs modulus (E) and the shear wave speed (Vs), (i.e., E-V relation), of tendon is still difficult to formulate. In this study, five porcine tendons were used to test the correlation between the relation between shear wave speed and Youngs modulus in a normal and a collagenase-induced diseased model. The measurement of the Youngs modulus was accomplished on a step motor with a load cell. Different degrees of pre-loading ranging from 0.5 to 3N were used to change the elastic properties both in normal and diseased models. For each loading condition, a fully preprogrammed array system was used to generate and detect the shear wave speed. The measured Youngs modulus under different degrees of preloading are highly correlated with the shear wave speed in both normal and diseased models. The averaged correlation coefficients between the wave speed and elastic modulus in normal and diseased models are 0.97±0.02 and 0.99 ± 0.005, respectively. We further use a second order polynomial to model the E-Vs relation. The scaling coefficient was found to be 0.104 and 0.117, respectively, for the normal and the diseased model. When all data points were adopted in the fitting, the scaling coefficient was 0.107. Based on these results, we found that the E-Vs relation is similar in both the normal and diseased model. The shear wave speed can be an index for quantifying Youngs modulus of tendon. Our findings may provide a new strategy for tendon function investigation in clinical practice.

Tissue shear viscosity measurements using a spectral ratio method

Mechanical properties such as elasticity and viscosity are highly related to tissue pathology state. Images that provide the geometry information of an object as well as its shear elasticity and viscosity are important in clinical applications. In the supersonic shear imaging (SSI) technique, image reconstruction in an inhomogeneous medium could be performed by varying the reconstruction kernel size, which in this article was regarded as the modified supersonic shear imaging (mSSI) method. In this study, we proposed a spectral ratio (SR) method for the reconstruction of shear elasticity and viscosity images. The reconstruction performance of an embedded object was evaluated for three different sizes of kernels, which were 0.308, 1.84 and 3.08 mm with comparison with the results obtained by the SSI method. The mean elasticity and viscosity error in the best reconstruction case using the SR method was 3.2% and 28.45%, respectively, while the mean elasticity and viscosity error in the best case using modify spectroscopy method is 19.56% and 26.36%, respectively. Both SR and mSSI method could provide boundary information of the embedded object. The SR method could achieve a spatial resolution of 0.308 mm in both elasticity and viscosity reconstruction.

Effects of Extracorporeal Shock Wave-Mediated Transdermal Local Anesthetic Drug Delivery on Rat Caudal Nerves

Cavitation plays a substantial role in the clinical effects of extracorporeal shock wave therapy (ESWT). It is also generally accepted as a major mechanism in sonophoresis. To identify the enhancing effect of extracorporeal shock wave-mediated transdermal drug delivery, 24 Wistar rats were randomly assigned to four groups: (i) topical application of a eutectic mixture of local anesthetics (EMLA); (ii) 1-MHz ultrasound; (iii) ESWT pre-treatment combined with EMLA application; (iv) ESWT concurrent with EMLA application on rat tails. The degree of anesthesia was assessed using the amplitude and latency of sensory nerve action potentials within 5 min after a 60-min EMLA application. The results indicated that ESWT pre-treatment and concurrent ESWT accelerated the anesthetic effects of the EMLA cream on the tail nerve (p < 0.05). This finding might indicate that shock wave-mediated transdermal drug delivery is possible during the ESWT period.