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Title: Liver fibrosis assessment using transient elastography guided with real-time B-mode ultrasound imaging : a feasibility study
Authors: Mak, Tak-man
Degree: M.Phil.
Issue Date: 2013
Abstract: Liver fibrosis is a kind of chronic damage of the liver and may lead to cirrhosis, one of the top 10 causes of death in the western world. The complications of cirrhosis may include liver failure, portal hypertension and hepatocellular carcinoma. The main causes of liver fibrosis are very common including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcohol abuse and non-alcoholic steatohepatitis (NASH). Thus, the demand for a noninvasive diagnostic system is high. Recently, a device called Fibroscan (Echosens, Paris, France) has been developed based on transient elastography, which shows promising results for liver fibrosis assessment. However, this device does not provide visual guidance of the liver during measurement, which affects the measurement accuracy and user-friendliness of operation. Our team has also developed a transient elastography system with real-time B-mode ultrasound imaging serving as visual guidance for liver fibrosis assessment, named as Liverscan. The aims of this MPhil study are (1) to design and fabricate specific probe for Liverscan to assess liver fibrosis non-invasively; (2) to systematically validate the new system and (3) to establish a measurement protocol for using the system. The measurement probe was designed and fabricated with a B-mode ultrasound transducer (4.5 MHz) fixed along the axis of a mechanical vibrator. When the mechanical vibrator was activated, the ultrasound transducer vibrated accordingly to generate shear wave in tissue. The vibration frequency used in this study was 100 Hz and its amplitude was approximately 5 mm at the surface of the transducer, which were optimal for this system. The induced shear wave propagated through liver tissue; pulse-echo ultrasound acquisition was used to trace the shear wave. The propagation of the shear wave in tissue indicates the stiffness of liver. A higher shear wave velocity indicates a harder liver tissue that reveals the severity of fibrosis. The measurement using Liverscan was validated by conventional mechanical indentation test on 15 custom-made agar-gelatin phantoms with different stiffness. An Instron machine was used to measure the force-indentation relationship of phantoms, and then their Young's modulus values were calculated and compared with the results obtained by Liverscan. A significant linear correlation of Young's moduli measured by the mechanical indentation test and the Liverscan (r=0.97, p<0.001) was found. This indicated that Liverscan was able to differentiate soft tissues with various stiffness. In this study, totally 67 subjects including 34 male and 33 female (Age: 34±13 years and BMI: 21.3±2.8 kgm²) were recruited for different tests. Among them, 20 subjects had confirmed liver diseases while the rest has no history of any liver disease. 26 and 23 subjects participated in inter- and intra-observer tests for the Liverscan, respectively. 28 subjects were tested using both Liverscan and Fibroscan. In addition, all the 67 subjects participated in the test of location dependence using Liverscan.
For the in vivo measurement using Liverscan, the subjects were tested using the following protocol. All the subjects fasted for at least 3 hours prior to any measurements. During the tests, the subjects were asked to lie down in supine position with their right arms in maximal abduction and placed behind their heads. Then, an area close to the projection of the rib cage was identified, i.e. the intercostal space between the 7th and 8th ribs and about 5 cm in distance from the projection. After the suitable location was identified, the measurement probe was applied. With the guidance of real-time B-mode ultrasound, we could select the depth and location of liver tissue to be assessed without any large blood vessels included by moving the cursor of region of interest (ROI). For the intra-observer test, the test was repeated by the same operator twice following the same protocol. The tests were conducted by two operators in the inter-operator test. In addition to the first location, another one was selected for applying the measurement probe to test the location dependence, which was at the intercostal space between 8th and 9th ribs. After the measurement using Liverscan, the selected subjects were tested again by the Fibroscan within one week at the centre of The Hong Kong Health Check. All the subjects fasted at least 3 hours before the measurement, and they were tested by the same operator at the centre. The results showed excellent repeatability of the measurement using Liverscan with an intraclass correlation coefficient of 0.987 (p<0.001) and 0.988 (p<0.001) for the inter- and intra-observer tests, respectively. A high correlation between the liver stiffness values obtained by the Liverscan and the Fibroscan was found (r=0.886, p<0.001). This indicated that the Liverscan was able to perform reliable in vivo liver stiffness measurement and capable of identifying liver with different stiffness. Based on the correlation and the result published for Fibroscan measurement, the calculated cut-off value of liver fibrosis was 14.0 kPa for the Liverscan. The location dependence test revealed no significant difference in the stiffness between the two tested sites (p=0.178) and the two sets of stiffness data showed significant correlation (r=0.946, p<0.001). This result demonstrated that both the locations were qualified to be included in the measurement protocol of the Liverscan. In summary, this study has demonstrated that the Liverscan with a specifically designed B-mode probe is able to provide a reliable measuement of livers with different stiffness using the proposed measurement protocol. The real-time B-mode ultrasound imaging is useful as visual guidance which improves the measurment accuracy and efficiency. Furture studies are required to further validate the system and demonstrate its clinical value by testing a large group of subjects with different degrees of liver fibrosis and by making comparison with biopsy.
Subjects: Liver -- Fibrosis.
Hong Kong Polytechnic University -- Dissertations
Pages: xix, 96 leaves : ill. ; 30 cm.
Appears in Collections:Thesis

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