Investigation Of Tissue Elasticity Measurements Using Shear Wave Ultrasound Elastography

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1 Investigation Of Tissue Elasticity Measurements Using Shear Wave Ultrasound Elastography Poster No.: C-1915 Congress: ECR 2014 Type: Scientific Exhibit Authors: H. E. Ting, C. H. Yeong, B. J. J. Abdullah, K. H. Ng; Kuala Lumpur/ MY Keywords: Tissue characterisation, Cirrhosis, Cancer, Experimental investigations, Equipment, Diagnostic procedure, Ultrasound, Experimental, Elastography, Ultrasound physics, Oncology DOI: /ecr2014/C-1915 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 26

2 Aims and objectives Introduction Elasticity imaging, otherwise known as elastography, plays a significant role in the application of clinical diagnosis by providing useful structural and pathological information on the elastic properties of tissue in the body. Many pathological processes such as inflammation and tumours can alter tissue elasticity significantly [Krouskop, 1998]. For example, most cancers, such as scirrhous carcinoma of the breast, appear to be very stiff compared to normal tissue [Anderson, 1953]. One of the latest developments in elastography imaging is Shear Wave Elastography (SWE) (Refer to Fig.1) which uses ultrafast ultrasound to measure tissue elasticity in a selected area. It is a real-time, non-invasive and reproducible method to map tissue stiffness of the entire region of interest (ROI). The process of SWE is demonstrated in Fig.2. In SWE, a transient pulse is sent out from the probe to push the underlying tissue, causing the underlying tissue to deform or displace. Human tissues, which are elastic, will oppose the push by a restoring force which subsequently generates transverse shear wave fronts propagating in opposite direction. The propagation of shear wave is then captured using ultrafast technology in which a flat ultrasound wave is sent out to insonify the whole medium in one shot. The propagation of shear wave in the medium is then captured just like a movie from which its velocity can be estimated. From equation 1, the elasticity of the tissue (Young's modulus) can be computed [Bercoff, 2008]. 2 E = 3#c Equation (1) -3 where # is the local density (constant and equal to 1000 kg m in soft tissue) and is the shear wave propagation velocity). Objectives This study aimed to verify the accuracy of SWE measurement in a gelatine-based elasticity phantom by comparing the elasticity measurements with a gold standard and investigate the effect of masses' depth, size and elasticity on the SWE measurements. Page 2 of 26

3 Images for this section: Page 3 of 26

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5 Fig. 1: ShearWave Elastography system developed by Supersonic Imagine Company, USA Fig. 2: SWE process involves non invasive procedure in 3 main steps: generation of a shear wave, capture of a shear wave and quantification of shear wave speed to give local elasticity value of tissues (Young's Modulus) Page 5 of 26

6 Methods and materials The methodology of this research can be divided into two parts. Fig.3 summarises the flow of the methodology of this study. 1. Phantom construction 1.1 Phantoms for calibration of elasticity The phantoms were constructed to give guidelines as to how much gelatine needs to be added to produce phantoms within required range of elasticity. Each phantom was constructed without any internal inclusions in them. Different amount of gelatines (8 to 24 g with 4 g increasing step) were dissolved in 150 ml of water and mixed together with 0.5 g of calcium carbonate (CaCO3) which acts as scatterers in a beaker. The solution was heated on a hot plate and stirred continuously until everything dissolved into molten gelatine as shown in Fig.4. The molten gelatine was then poured into containers and left to set as shown in Fig Phantom for comparison between SWE and gold standard Five spherical inclusions with different elasticity were constructed using different amount of gelatine (8 to 24 g with 4 g increasing step) mixed with 0.5 g of CaCO3 and 150 ml of water. 2 hemispherical moulds were submerged into the red molten gelatine and clamped together to form the spherical inclusions as shown in Fig.6. The inclusions were then incorporated into the phantom to represent different elasticity of lesions. The final product of the phantom was shown in Fig Phantoms for investigations of factors affecting SWE A phantom consisting of inclusions of varying sizes, elasticity and depth was constructed to explore the factors affecting elasticity measurement. The calibration phantom was constructed according to the schematic diagram shown in Fig.8 and the specifications were listed in Table 1. In addition, another phantom was made to compare the elasticity of spherical and cylindrical inclusions. Five cylindrical and spherical inclusions of different elasticity were embedded in a homogenous background as shown in Fig.9 2. Elasticity measurements 2.1 With SWE Page 6 of 26

7 The elasticity of the phantoms was first measured using SWE. All the phantoms were scanned with the SWE probe and the SWE colour map was displayed in real time. The ROI was placed on the inclusions and the value of its elasticity was displayed as shown in Fig With the gold standard The gold standard to verify the SWE measurement was a calibrated material microtester system (model 5848, Instron Co, USA). After the measurements with SWE, the inclusions were extracted from the phantom and cut into cylindrical shapes (the Instron can only test cylindrical samples) to be tested on the Instron. A graph of stress vs. strain was displayed in real time where the initial slope gives the Young's modulus of the tested samples as shown in Fig Comparison of SWE with the Gold Standard The elasticity of each phantom measured by the SWE and the Instron were presented in graphical forms and their relationships were studied and observed by means of statistical analysis. Images for this section: Page 7 of 26

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9 Fig. 1: ShearWave Elastography system developed by Supersonic Imagine Company, USA Fig. 2: SWE process involves non invasive procedure in 3 main steps: generation of a shear wave, capture of a shear wave and quantification of shear wave speed to give local elasticity value of tissues (Young's Modulus) Fig. 3: Flow chart showing the methodology of the study Page 9 of 26

10 Fig. 4: Schematic diagram of the experimental setup to make gelatine for the phantom Fig. 5: Molten gelatine of different amount of gelatine added were poured into different containers and left to congeal. Page 10 of 26

11 Fig. 6: (a) Two parts hemispherical moulds were immersed in red molten gelatine, clamped together with masking tape and left to set to form spherical inclusions. (b) After the gelatine had congealed, the two parts moulds were separated carefully and the spherical inclusion formed was taken out. (c) The spherical inclusions of diameter 2.6 cm. Page 11 of 26

12 Fig. 7: The final product of the phantom Page 12 of 26

13 Fig. 8: (a) Schematic diagram of the phantom from the top view (b) from the front view (c) final product of the phantom from top view (d) front view Page 13 of 26

14 Table 1: Specifications of each inclusion in the calibration phantom Page 14 of 26

15 Fig. 9: (a) Schematic diagram of the side view of the phantom. Three spherical and cylindrical inclusions pairs were placed on the first layer of gelatine in the front row. The other two pairs were hidden at the back row. The inclusions were then covered with second layer and third layer of gelatine. (b) The final product of the phantom from the top view. Page 15 of 26

16 Fig. 10: The ROI was placed on the inclusions to measure its elasticity. The colour scale on the top right depicts quantitative values of elasticity shown in the ROI. Page 16 of 26

17 Fig. 11: (a) Cylindrical-shaped samples for the compressive test. (b) The cylindrical sample was placed in between the two plates to be compressed slowly by the upper plate. The displacement of the samples was calculated by the system software and the graph of stress vs. strain was displayed in real time on the monitor by the software. (c) The initial slope of the graph of stress vs. strain gives the Young's modulus of the tested samples. Page 17 of 26

18 Results Calibration of Phantom Elasticity Fig.12 shows the SWE mode overview of background phantom with 4, 8, 12, 16, 20 and 24 g of gelatine added. The colour scale on the top right depicts quantitative values of elasticity shown in the ROI while the qualitative values of elasticity measured in each ROIs were displayed on the right. The values of the elasticity were shown in three ways: mean, min and max. The mean elasticity values were taken into account as it is the most relevant values. Fig.13 shows the relationship between mass of gelatine added into the phantoms and the mean elasticity value the phantoms give. It can be observed that the mean elasticity increases linearly with the amount of gelatine added. The coefficient of determination, 2 R was 0.983, which means that 98.3% of the total variation in mean elasticity can be explained by the linear relationship between mean elasticity and mass of gelatine added. This showed a rather strong correlation between the mean elasticity of the phantom and the mass of gelatine added, indicating that mass of gelatine added was useful as a predictor for the phantom's mean elasticity from the calibration graph. Comparison between SWE and the gold standard Fig.14 shows the relationship between mass of gelatine added into spherical inclusions and the mean elasticity measured using SWE and Instron microtester. It can be observed that the mean elasticity increases linearly with mass of gelatine added for both methods of measurements. However, the elasticity measurements by Instron microtester were always lower than the elasticity measurements by SWE. The p-value was smaller than Therefore, it can be concluded that there was a statistically significant difference between both method. As the mean elasticity measured by SWEwas always greater than the measurements made by Instron microtester, it can be said that the elasticity measurement made by SWEwas an overestimation of the actual elasticity by 7 to 39 kpa. This overestimation was probably contributed by the assumption made by the SWE -3 system that all density of tissue in the body equals to 1 g cm. In reality, the density of human tissue differs slightly from one another, depending on the types of tissue [Farvid, 2005; Ward, 2005]. Investigation of Factors Affecting the Elasticity Measurements Page 18 of 26

19 Fig.15 shows how different sizes of inclusions affect the SWE measurements. It can be observed from the Fig.15 that the elasticity of different sizes inclusions did not vary much, with standard deviations of among the measured elasticity. However the error bars of each measurement appeared to be quite large but they all overlap with one another. This indicated that there was a much lower likelihood that the elasticity values differ significantly from one another. Fig.16 shows how inclusions at different depth affect the SWE measurements. Only three inclusions closest to the surface of the phantom (2.7, 4.7 and 6.7 cm from the surface) could be measured probably because the transducer (15 MHz) used was designed for superficial measurement of up to 7 cm depth. Due to lack of data, the effect of depth on elasticity was inconclusive. Therefore, repetition of measurement is needed to investigate this effect. Fig.17 shows that the elasticity increases with increasing mass of gelatine added to the inclusions. Different amount of gelatine was added to the inclusions to produce inclusions with different stiffness. The more gelatine was added into the inclusions, the stiffer the inclusions would be. Fig.18 shows the relationship between mass of gelatine added and mean elasticity measured using SWE for cylindrical and spherical inclusions. The graph shows a linear relationship between the mass of gelatine and mean elasticity for both shapes of inclusions. It can be observed that the mean elasticity of cylindrical inclusions was always lower than the mean elasticity of the spherical inclusions for the same mass of gelatine added. However, as the mass of gelatine added increases, both graphs converge and finally meet at 125 kpa at 24 g of gelatine added. The p-value was greater than Therefore, it was concluded that there is no statistically significant difference between the mean elasticity of the cylindrical and spherical inclusions. Further works need to be done to find the factors of the overestimation. Images for this section: Page 19 of 26

20 Fig. 12: (a) The top image shows the SWE mode of the background phantom with 4 g of gelatine added. 4 ROIs measuring 3 mm of diameter were placed on the phantom to quantify their respective elasticities which were displayed on the right side of the monitor. The ROI appear blue which according to the colour scale at the upper right corner, means very low elasticity. The bottom image shows the phantom in B-mode. (b) 8 g of gelatine added (c) 12 g of gelatine added (d) 16 g of gelatine added (e) 20 g of gelatine added (f) 24 g of gelatine added. Page 20 of 26

21 Fig. 13: Graph of elasticity calibration of phantom Fig. 14: Graph of comparison in elasticity measurements between SWE and Instron microtester for spherical inclusions. Page 21 of 26

22 Fig. 15: Graph that shows effect of the size of the inclusions on the elasticity measured by SWE. Fig. 16: Graph shows the effect of the depth of the inclusions on the elasticity measured by SWE. Page 22 of 26

23 Fig. 17: Graph that shows the effect of the mass of gelatine added to the inclusions on the elasticity measured by SWE. Page 23 of 26

24 Fig. 18: Graph of comparison between the elasticity values of cylindrical and spherical inclusions. Page 24 of 26

25 Conclusion The main objective of this study, which was to investigate tissue elasticity measurement using SWE has been achieved. An elasticity calibration curve had been constructed to give the reference elasticity values based on the amount of gelatine added. The calibration curve gave a linear relationship between the elasticity and the mass of gelatine and both the variables were proven to be strongly corelated. A homogenous phantom that simulates lesions of varying sizes, stiffness and depth had been constructed to investigate the factors affecting the elasticity. This study showed that masses of varying sizes had no significant effect on the elasticity values given by the SWE. However, depth of the masses does not have conclusive influence on the elasticity measured, due to lack of data. Cylindrical and spherical masses had also been incorporated in the phantom to explore the effect of shape on the SWE measurement. The paired T-test showed that there was no significant difference between elasticity of cylindrical and spherical masses. The elasticity of the spherical masses had been measured by SWE and the gold standard and then compared. It was observed that the elasticity measured by SWE is always greater than the elasticity measured by the gold standard. A paired sample t-test had been performed and results showed that there was a significant difference between the elasticity values given by the SWE and the gold standard. Thus, it can be concluded that the elasticity measurement by SWE was an overestimation of the actual elasticity by an unknown factor which needs further investigation. Personal information Huong Eng Ting, MMedPhys huong.eng207@gmail.com Chai Hong Yeong, PhD, MMedPhys, BSc chyeong@um.edu.my Basri JJ Abdullah basrij@ummc.edu.my Kwan Hoong Ng ngkh@ummc.edu.my Page 25 of 26

26 Department of Biomedical Imaging and University of Malaya Reserach Imaging Centre, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia References Krouskop, T. A., Wheeler, T. M., Kllel, F., Garra, B. S., Hall, T. (1998) Elastic moduli of breast and prostate tissues under compression. Ultrasonic imaging, 20, Anderson, W. A. D. (1953). Pathology. St. Louis: C.V. Mosby Co. TM Bercoff, J. (2008). ShearWave Elastography. SuperSonic Imagine, S.A. Farvid, M. S., Ng, T. W. K, Chan, D. C., Barrett, P. H. R, Watts, G. F. (2005). Association of adiponectin and resistin with adipose tissue compartments, insulin resistance and dyslipidaemia. Diabetes, Obesity and Metabolism, 7(4), Ward, S. R, Lieber, R. L. (2005). Density and hydration of fresh and fixed human skeletal muscle. Journal of Biomechanics, 38(11), Page 26 of 26