Experimental studies for noninvasive assessment of portal vein pressure based on contrast enhanced subharmonic sonographic imaging_Journal of Biomedical Engineering

Authors：

XIANG Heng ¹ , YANG Rui ² ,  ZOU Yuanwen ¹ , LU Qiang ² , CHEN Ke ¹

1. Department of Biomedical Engineering, College of Materials Science & Engineering, Sichuan University, Chengdu 610065, P.R.China;
2. Department of Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, P.R.China;

Corresponding author：

ZOU Yuanwen, Email: zyw@scu.edu.cn

Keywords：

portal vein pressure; subharmonic; noninvasive; ultrasound contrast agent; linear regression

DOI：

10.7507/1001-5515.202003002

Video：

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Portal hypertension (PHT) is a common complication of liver cirrhosis, which could be measured by the means of portal vein pressure (PVP). However, there is no report about an effective and reliable way to achieve noninvasive assessment of PVP so far. In this study, firstly, we collected ultrasound images and echo signals of different ultrasound contrast agent (UCA) concentrations and different pressure ranges in a low-pressure environment based on an in vitro simulation device. Then, the amplitudes of the subharmonics in the echo signal were obtained by ultrasound grayscale image construction and fast Fourier transform (FFT). Finally, we analyzed the relationship between subharmonic amplitude (SA) and bionic portal vein pressure (BPVP) through linear regression. As a result, in the pressure range of 7.5–45 mm Hg and 8–20 mm Hg, the linear correlation coefficients (LCC) between SA and BPVP were 0.927 and 0.913 respectively when the UCA concentration was 1∶3 000, and LCC were 0.737 and 0.568 respectively when the UCA concentration was 1∶6 000. Particularly, LCC was increased to 0.968 and 0.916 respectively while the SAs of two UCA concentrations were used as the features of BPVP. Therefore, the results show a good performance on the linear relationship between SA and BPVP, and the LCC will be improved by using SAs obtained at different UCA concentrations as the features of BPVP. The proposed method provides reliable experimental verification for noninvasive evaluation of PVP through SA in clinical practice, which could be a guidance for improving the accuracy of PVP assessment.

Citation： XIANG Heng, YANG Rui, ZOU Yuanwen, LU Qiang, CHEN Ke. Experimental studies for noninvasive assessment of portal vein pressure based on contrast enhanced subharmonic sonographic imaging. Journal of Biomedical Engineering, 2020, 37(6): 1073-1079. doi: 10.7507/1001-5515.202003002 Copy

1.	Qi X, Berzigotti A, Cardenas A, et al. Emerging non-invasive approaches for diagnosis and monitoring of portal hypertension. Lancet Gastroenterol Hepatol, 2018, 3(10): 708-719.
2.	宋珂达, 姜洪池. 门静脉压力无创测定应给予重视. 中华普通外科学文献(电子版), 2018, 12(6): 373-375.
3.	Bolognesi M, Di Pascoli M, Sacerdoti D. Clinical role of non-invasive assessment of portal hypertension. World J Gastroenterol, 2017, 23(1): 15-24.
4.	Ravaioli F, Montagnani M, Lisotti A, et al. Noninvasive assessment of portal hypertension in advanced chronic liver disease: An update. Gastroenterol Res Prac, 2018, 2018: 1-11.
5.	Thabut D, Moreau R, Lebrec D. Noninvasive assessment of portal hypertension in patients with cirrhosis. Hepatology, 2011, 53(2): 683-694.
6.	Addley J, Tham T C, Cash W J. Use of portal pressure studies in the management of variceal haemorrhage. World J Gastrointest Endosc, 2012, 4(7): 281-289.
7.	Leung J C-F, Loong T C-W, Pang J, et al. Invasive and non-invasive assessment of portal hypertension. Hepatol Int, 2018, 12: 44-55.
8.	Levick C, Phillips-Hughes J, Collier J, et al. Non-invasive assessment of portal hypertension by multi-parametric magnetic resonance imaging of the spleen: A proof of concept study. PLoS ONE, 2019, 14(8): e0221066.
9.	Wang J, Gao F, Shen J L. Noninvasive assessment of portal hypertension using spectral computed tomography. J Clin Gastroenterol, 2019, 53(9): e387-e391.
10.	Roccarina D, Rosselli M, Genesca J, et al. Elastography methods for the non-invasive assessment of portal hypertension. Expert Rev Gastroenterol Hepatol, 2018, 12(2): 155-164.
11.	Elmahdy A M, Berzigotti A. Non-invasive measurement of portal pressure. Curr Hepat Rep, 2019, 18: 20-27.
12.	Leeming D J, Veidal S S, Karsdal M A, et al. Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis. Scand J Gastroenterol, 2015, 50(5): 584-592.
13.	La Mura V, Reverter J C, Flores-Arroyo A, et al. Von Willebrand factor levels predict clinical outcome in patients with cirrhosis and portal hypertension. Gut, 2011, 60(8): 1133-1138.
14.	Zhang Q W, Wang Y, Wang J, et al. A non-invasive magnetic resonance imaging-based model predicts portal venous pressure. J Digest Dis, 2016, 17(3): 175-185.
15.	Chen J, Yin M, Talwalkar J A, et al. Diagnostic performance of MR elastography and vibration-controlled transient elastography in the detection of hepatic fibrosis in patients with severe to morbid obesity. Radiology, 2016: 160685.
16.	Andaluz I, Abadía M, Ponce D, et al. SAT-409-Hepatic vein arrival time assessed by contrast-enhanced ultrasound in the non-invasive evaluation of portal hypertension. J Hepatol, 2019, 70(1): e813.
17.	Ferraioli G, Tinelli C, Dal Bello B, et al. Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: A pilot study. Hepatology, 2012, 56(6): 2125-2133.
18.	Xie Limei. Real-time elastography for diagnosis of liver fibrosis in chronic hepatitis B. J Ultrasound Med, 2012, 31(7): 1053-1060.
19.	Wiechowska-Kozłowska A, Zasada K, Milkiewicz M, et al. Correlation between endosonographic and Doppler ultrasound features of portal hypertension in patients with cirrhosis. Gastroenterol Res Prac, 2012, 2012(1): 395345.
20.	Elwan N, Salah R, Hamisa M, et al. Evaluation of portal pressure by Doppler ultrasound in patients with cirrhosis before and after simvastatin administration - a randomized controlled trial. F1000 Res, 2018, 7: 256.
21.	Postema M, Gilja O H. Contrast-enhanced and targeted ultrasound. World J Gastroenterol, 2011, 17(1): 28-41.
22.	Jansen C, Bogs C, Verlinden W, et al. Shear-wave elastography of the liver and spleen identifies clinically significant portal hypertension: A prospective multicentre study. Liver Int, 2017, 37(3): 396-405.
23.	吕道文, 张拥军, 赵挺, 等. 超声造影剂微泡次谐波辅助压力估测技术研究进展. 中国医学物理学杂志, 2016, 33(9): 959-962.
24.	Eisenbrey J R, Dave J K, Halldorsdottir V G, et al. Chronic liver disease: Noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology, 2013, 268(2): 581-588.
25.	Li F, Li D, Yan F. Improvement of detection sensitivity of microbubbles as sensors to detect ambient pressure. Sensors, 2018, 18(12): 4083.
26.	Shi W T, Forsberg F, Raichlen J S, et al. Pressure dependence of subharmonic signals from contrast microbubbles. Ultrasound Med Biol, 1999, 25(2): 275-283.
27.	Leodore L M, Forsberg F, Shi W T. P5B-6 in vitro pressure estimation obtained from subharmonic contrast microbubble signals//2007 IEEE Ultrasonics Symposium. New York: IEEE, 2007: 2207-2210.
28.	Andersen K S, Jensen J A. Impact of acoustic pressure on ambient pressure estimation using ultrasound contrast agent. Ultrasonics, 2010, 50(2): 294-299.
29.	Sun T, Jia N, Zhang D, et al. Ambient pressure dependence of the ultra-harmonic response from contrast microbubbles. J Acoust Soc Am, 2012, 131(6): 4358.
30.	Wu Jun, Fan Tingbo, Xu Di, et al. Investigation on the relationship between overpressure and sub-harmonic response from encapsulated microbubbles. Chin Phys B, 2014, 23(10): 104302.
31.	李德玉, 李飞, 樊瑜波, 等. 基于微泡超声造影剂的血压无创测量装置: CN101982156B. 2010.
32.	李飞. 基于超声造影剂次谐波的无创血压测量方法研究. 北京: 北京航空航天大学, 2012.
33.	Dave J K, Halldorsdottir V G, Eisenbrey J R, et al. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC-Cardiovasc Imag, 2012, 5(1): 7-92.
34.	黄韫栀, 刘奇, 肖勇. 基于超声RF信号的超声成像实验设计. 实验科学与技术, 2016, 14(6): 32-35, 84.
35.	周志华. 机器学习. 北京: 清华大学出版社, 2016.

1. Qi X, Berzigotti A, Cardenas A, et al. Emerging non-invasive approaches for diagnosis and monitoring of portal hypertension. Lancet Gastroenterol Hepatol, 2018, 3(10): 708-719.
2. 宋珂达, 姜洪池. 门静脉压力无创测定应给予重视. 中华普通外科学文献(电子版), 2018, 12(6): 373-375.
3. Bolognesi M, Di Pascoli M, Sacerdoti D. Clinical role of non-invasive assessment of portal hypertension. World J Gastroenterol, 2017, 23(1): 15-24.
4. Ravaioli F, Montagnani M, Lisotti A, et al. Noninvasive assessment of portal hypertension in advanced chronic liver disease: An update. Gastroenterol Res Prac, 2018, 2018: 1-11.
5. Thabut D, Moreau R, Lebrec D. Noninvasive assessment of portal hypertension in patients with cirrhosis. Hepatology, 2011, 53(2): 683-694.
6. Addley J, Tham T C, Cash W J. Use of portal pressure studies in the management of variceal haemorrhage. World J Gastrointest Endosc, 2012, 4(7): 281-289.
7. Leung J C-F, Loong T C-W, Pang J, et al. Invasive and non-invasive assessment of portal hypertension. Hepatol Int, 2018, 12: 44-55.
8. Levick C, Phillips-Hughes J, Collier J, et al. Non-invasive assessment of portal hypertension by multi-parametric magnetic resonance imaging of the spleen: A proof of concept study. PLoS ONE, 2019, 14(8): e0221066.
9. Wang J, Gao F, Shen J L. Noninvasive assessment of portal hypertension using spectral computed tomography. J Clin Gastroenterol, 2019, 53(9): e387-e391.
10. Roccarina D, Rosselli M, Genesca J, et al. Elastography methods for the non-invasive assessment of portal hypertension. Expert Rev Gastroenterol Hepatol, 2018, 12(2): 155-164.
11. Elmahdy A M, Berzigotti A. Non-invasive measurement of portal pressure. Curr Hepat Rep, 2019, 18: 20-27.
12. Leeming D J, Veidal S S, Karsdal M A, et al. Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis. Scand J Gastroenterol, 2015, 50(5): 584-592.
13. La Mura V, Reverter J C, Flores-Arroyo A, et al. Von Willebrand factor levels predict clinical outcome in patients with cirrhosis and portal hypertension. Gut, 2011, 60(8): 1133-1138.
14. Zhang Q W, Wang Y, Wang J, et al. A non-invasive magnetic resonance imaging-based model predicts portal venous pressure. J Digest Dis, 2016, 17(3): 175-185.
15. Chen J, Yin M, Talwalkar J A, et al. Diagnostic performance of MR elastography and vibration-controlled transient elastography in the detection of hepatic fibrosis in patients with severe to morbid obesity. Radiology, 2016: 160685.
16. Andaluz I, Abadía M, Ponce D, et al. SAT-409-Hepatic vein arrival time assessed by contrast-enhanced ultrasound in the non-invasive evaluation of portal hypertension. J Hepatol, 2019, 70(1): e813.
17. Ferraioli G, Tinelli C, Dal Bello B, et al. Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: A pilot study. Hepatology, 2012, 56(6): 2125-2133.
18. Xie Limei. Real-time elastography for diagnosis of liver fibrosis in chronic hepatitis B. J Ultrasound Med, 2012, 31(7): 1053-1060.
19. Wiechowska-Kozłowska A, Zasada K, Milkiewicz M, et al. Correlation between endosonographic and Doppler ultrasound features of portal hypertension in patients with cirrhosis. Gastroenterol Res Prac, 2012, 2012(1): 395345.
20. Elwan N, Salah R, Hamisa M, et al. Evaluation of portal pressure by Doppler ultrasound in patients with cirrhosis before and after simvastatin administration - a randomized controlled trial. F1000 Res, 2018, 7: 256.
21. Postema M, Gilja O H. Contrast-enhanced and targeted ultrasound. World J Gastroenterol, 2011, 17(1): 28-41.
22. Jansen C, Bogs C, Verlinden W, et al. Shear-wave elastography of the liver and spleen identifies clinically significant portal hypertension: A prospective multicentre study. Liver Int, 2017, 37(3): 396-405.
23. 吕道文, 张拥军, 赵挺, 等. 超声造影剂微泡次谐波辅助压力估测技术研究进展. 中国医学物理学杂志, 2016, 33(9): 959-962.
24. Eisenbrey J R, Dave J K, Halldorsdottir V G, et al. Chronic liver disease: Noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology, 2013, 268(2): 581-588.
25. Li F, Li D, Yan F. Improvement of detection sensitivity of microbubbles as sensors to detect ambient pressure. Sensors, 2018, 18(12): 4083.
26. Shi W T, Forsberg F, Raichlen J S, et al. Pressure dependence of subharmonic signals from contrast microbubbles. Ultrasound Med Biol, 1999, 25(2): 275-283.
27. Leodore L M, Forsberg F, Shi W T. P5B-6 in vitro pressure estimation obtained from subharmonic contrast microbubble signals//2007 IEEE Ultrasonics Symposium. New York: IEEE, 2007: 2207-2210.
28. Andersen K S, Jensen J A. Impact of acoustic pressure on ambient pressure estimation using ultrasound contrast agent. Ultrasonics, 2010, 50(2): 294-299.
29. Sun T, Jia N, Zhang D, et al. Ambient pressure dependence of the ultra-harmonic response from contrast microbubbles. J Acoust Soc Am, 2012, 131(6): 4358.
30. Wu Jun, Fan Tingbo, Xu Di, et al. Investigation on the relationship between overpressure and sub-harmonic response from encapsulated microbubbles. Chin Phys B, 2014, 23(10): 104302.
31. 李德玉, 李飞, 樊瑜波, 等. 基于微泡超声造影剂的血压无创测量装置: CN101982156B. 2010.
32. 李飞. 基于超声造影剂次谐波的无创血压测量方法研究. 北京: 北京航空航天大学, 2012.
33. Dave J K, Halldorsdottir V G, Eisenbrey J R, et al. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC-Cardiovasc Imag, 2012, 5(1): 7-92.
34. 黄韫栀, 刘奇, 肖勇. 基于超声RF信号的超声成像实验设计. 实验科学与技术, 2016, 14(6): 32-35, 84.
35. 周志华. 机器学习. 北京: 清华大学出版社, 2016.

Journal of Biomedical Engineering

Experimental studies for noninvasive assessment of portal vein pressure based on contrast enhanced subharmonic sonographic imaging

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