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Published in: Digestive Diseases and Sciences 12/2021

01-12-2021 | Ultrasound | Original Article

Hepatic Vein Contrast-Enhanced Ultrasound Subharmonic Imaging Signal as a Screening Test for Portal Hypertension

Authors: Priscilla Machado, Ipshita Gupta, Sriharsha Gummadi, Maria Stanczak, Corinne E. Wessner, Jonathan M. Fenkel, Colette M. Shaw, Susan Shamini-Noori, Susan Schultz, Michael C. Soulen, Chandra M. Sehgal, Kirk Wallace, John R. Eisenbrey, Flemming Forsberg

Published in: Digestive Diseases and Sciences | Issue 12/2021

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Abstract

Background

Portal hypertension is the underlying cause of most complications associated with cirrhosis, with the hepatic venous pressure gradient (HVPG) used for diagnosis and disease progression. Subharmonic imaging (SHI) is a contrast-specific imaging technique receiving at half the transmit frequency resulting in better tissue suppression.

Aims

To determine whether the presence of optimized SHI signals inside the hepatic vein can be used as a screening test for portal hypertension.

Methods

This prospective trial had 131 patients undergoing SHI examination of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI). Images acquired after infusion of the ultrasound contrast agent Sonazoid (GE Healthcare, Oslo, Norway) were assessed for the presence of optimized SHI signals in the hepatic vein and compared to the HVPG values obtained as standard of care.

Results

Of 131 cases, 64 had increased HVPG values corresponding to subclinical (n = 31) and clinical (n = 33) portal hypertension (> 5 and > 10 mmHg, respectively), and 67 had normal HVPG values (< 5 mmHg). Two readers performed independent, binary qualitative assessments of the acquired digital clips. Reader one (experienced radiologist) achieved for the subclinical subgroup sensitivity of 98%, specificity of 88%, and ROC area of 0.93 and for the clinical subgroup sensitivity of 100% and specificity of 61%, with an ROC area of 0.74. Reader two (less experienced radiologist) achieved for the subclinical subgroup sensitivity of 77%, specificity of 76%, and ROC area of 0.76 and for the clinical subgroup sensitivity of 88% and specificity of 63%, with an ROC area of 0.70. Readers agreement was of 83% with kappa value of 0.66.

Conclusion

The presence of optimized SHI signals inside the hepatic vein can be a qualitative screening test for portal hypertension, which could reduce the need for invasive diagnostic procedures.
Literature
1.
go back to reference Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383:1749–1761.CrossRef Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383:1749–1761.CrossRef
2.
go back to reference Bosch J, Berzigotti A, Garcia-Pagan JC, Abraldes JG. The management of portal hypertension: rational basis, available treatments and future options. J Hepatol. 2008;48:S68–S92.CrossRef Bosch J, Berzigotti A, Garcia-Pagan JC, Abraldes JG. The management of portal hypertension: rational basis, available treatments and future options. J Hepatol. 2008;48:S68–S92.CrossRef
3.
go back to reference Bosch J, Abraldes JG, Fernández M, García-Pagán JC. Hepatic endothelial dysfunction and abnormal angiogenesis: new targets in the treatment of portal hypertension. J Hepatol. 2010;53:558–567.CrossRef Bosch J, Abraldes JG, Fernández M, García-Pagán JC. Hepatic endothelial dysfunction and abnormal angiogenesis: new targets in the treatment of portal hypertension. J Hepatol. 2010;53:558–567.CrossRef
4.
go back to reference Pinzani M, Rosselli M, Zuckermann M. Liver cirrhosis. Best Pract Res Clin Gastroenterol. 2011;25:281–290.CrossRef Pinzani M, Rosselli M, Zuckermann M. Liver cirrhosis. Best Pract Res Clin Gastroenterol. 2011;25:281–290.CrossRef
5.
go back to reference Berzigotti A, Seijo S, Reverter E, et al. Assessing portal hypertension in liver diseases. Expert Rev Gastroenterol Hepatol. 2013;7:141–155.CrossRef Berzigotti A, Seijo S, Reverter E, et al. Assessing portal hypertension in liver diseases. Expert Rev Gastroenterol Hepatol. 2013;7:141–155.CrossRef
6.
go back to reference Kim MY, Baik SK, Lee SS. Hemodynamic alterations in cirrhosis and portal hypertension. Korean J Hepatol. 2010;16:347.CrossRef Kim MY, Baik SK, Lee SS. Hemodynamic alterations in cirrhosis and portal hypertension. Korean J Hepatol. 2010;16:347.CrossRef
7.
go back to reference Groszmann RJ, Abraldes JG. Portal hypertension: from bedside to bench. J Clin Gastroenterol. 2005;39:S125–S130.CrossRef Groszmann RJ, Abraldes JG. Portal hypertension: from bedside to bench. J Clin Gastroenterol. 2005;39:S125–S130.CrossRef
8.
go back to reference Sanyal AJ, Bosch J, Blei A, Arroyo V. Portal hypertension and its complications. Gastroenterology. 2008;134:1715–1728.CrossRef Sanyal AJ, Bosch J, Blei A, Arroyo V. Portal hypertension and its complications. Gastroenterology. 2008;134:1715–1728.CrossRef
9.
10.
go back to reference D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217–231.CrossRef D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217–231.CrossRef
11.
go back to reference Schouten JN, Garcia-Pagan JC, Valla DC, Janssen HL. Idiopathic noncirrhotic portal hypertension. Hepatology. 2011;54:1071–1081.CrossRef Schouten JN, Garcia-Pagan JC, Valla DC, Janssen HL. Idiopathic noncirrhotic portal hypertension. Hepatology. 2011;54:1071–1081.CrossRef
12.
go back to reference Kumar A, Sharma P, Sarin SK. Hepatic venous pressure gradient measurement: time to learn. Indian J Gastroenterol. 2008;27:74–80.PubMed Kumar A, Sharma P, Sarin SK. Hepatic venous pressure gradient measurement: time to learn. Indian J Gastroenterol. 2008;27:74–80.PubMed
13.
go back to reference Londoño M-C, Cárdenas A, Guevara M, et al. MELD score and serum sodium in the prediction of survival of patients with cirrhosis awaiting liver transplantation. Gut. 2007;56:1283–1290.CrossRef Londoño M-C, Cárdenas A, Guevara M, et al. MELD score and serum sodium in the prediction of survival of patients with cirrhosis awaiting liver transplantation. Gut. 2007;56:1283–1290.CrossRef
14.
go back to reference Merli M, Nicolini G, Angeloni S, et al. Incidence and natural history of small esophageal varices in cirrhotic patients. J Hepatol. 2003;38:266–272.CrossRef Merli M, Nicolini G, Angeloni S, et al. Incidence and natural history of small esophageal varices in cirrhotic patients. J Hepatol. 2003;38:266–272.CrossRef
15.
go back to reference Kalambokis G, Manousou P, Vibhakorn S, et al. Transjugular liver biopsy–indications, adequacy, quality of specimens, and complications—a systematic review. J Hepatol. 2007;47:284–294.CrossRef Kalambokis G, Manousou P, Vibhakorn S, et al. Transjugular liver biopsy–indications, adequacy, quality of specimens, and complications—a systematic review. J Hepatol. 2007;47:284–294.CrossRef
16.
go back to reference Gupta I, Eisenbrey J, Stanczak M, et al. Effect of pulse shaping on subharmonic aided pressure estimation in vitro and in vivo. J Ultrasound Med. 2017;36:3–11.CrossRef Gupta I, Eisenbrey J, Stanczak M, et al. Effect of pulse shaping on subharmonic aided pressure estimation in vitro and in vivo. J Ultrasound Med. 2017;36:3–11.CrossRef
17.
go back to reference Dave JK, Kulkarni SV, Pangaonkar PP, et al. Non-invasive intra-cardiac pressure measurements using subharmonic-aided pressure estimation: proof of concept in humans. Ultrasound Med Biol. 2017;43:2718–2724.CrossRef Dave JK, Kulkarni SV, Pangaonkar PP, et al. Non-invasive intra-cardiac pressure measurements using subharmonic-aided pressure estimation: proof of concept in humans. Ultrasound Med Biol. 2017;43:2718–2724.CrossRef
18.
go back to reference Halldorsdottir VG, Dave JK, Marshall A, et al. Subharmonic-aided pressure estimation for monitoring interstitial fluid pressure in tumors: calibration and treatment with paclitaxel in breast cancer xenografts. Ultrasound Med Biol. 2017;43:1401–1410.CrossRef Halldorsdottir VG, Dave JK, Marshall A, et al. Subharmonic-aided pressure estimation for monitoring interstitial fluid pressure in tumors: calibration and treatment with paclitaxel in breast cancer xenografts. Ultrasound Med Biol. 2017;43:1401–1410.CrossRef
19.
go back to reference Halldorsdottir V, Dave J, Eisenbrey J, et al. Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours–in vitro and in vivo proof of concept. Ultrasonics. 2014;54:1938–1944.CrossRef Halldorsdottir V, Dave J, Eisenbrey J, et al. Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours–in vitro and in vivo proof of concept. Ultrasonics. 2014;54:1938–1944.CrossRef
20.
go back to reference Dave J, Halldorsdottir V, Eisenbrey J, et al. On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation. Ultrasonics. 2013;53:880–888.CrossRef Dave J, Halldorsdottir V, Eisenbrey J, et al. On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation. Ultrasonics. 2013;53:880–888.CrossRef
21.
go back to reference Dave JK, Halldorsdottir VG, Eisenbrey JR, et al. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC Cardiovasc Imaging. 2012;5:87–92.CrossRef Dave JK, Halldorsdottir VG, Eisenbrey JR, et al. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC Cardiovasc Imaging. 2012;5:87–92.CrossRef
22.
go back to reference Eisenbrey J, Dave J, Halldorsdottir V, et al. Simultaneous grayscale and subharmonic ultrasound imaging on a modified commercial scanner. Ultrasonics. 2011;51:890–897.CrossRef Eisenbrey J, Dave J, Halldorsdottir V, et al. Simultaneous grayscale and subharmonic ultrasound imaging on a modified commercial scanner. Ultrasonics. 2011;51:890–897.CrossRef
23.
go back to reference Dave JK, Forsberg F. Novel automated motion compensation technique for producing cumulative maximum intensity subharmonic images. Ultrasound Med Biol. 2009;35:1555–1563.CrossRef Dave JK, Forsberg F. Novel automated motion compensation technique for producing cumulative maximum intensity subharmonic images. Ultrasound Med Biol. 2009;35:1555–1563.CrossRef
24.
go back to reference Shi W, Forsberg F, Raichlen J, Needleman L, Goldberg B. Pressure dependence of subharmonic signals from contrast microbubbles. Ultrasound Med Biol. 1999;25:275–283.CrossRef Shi W, Forsberg F, Raichlen J, Needleman L, Goldberg B. Pressure dependence of subharmonic signals from contrast microbubbles. Ultrasound Med Biol. 1999;25:275–283.CrossRef
25.
go back to reference Forsberg F, Shi WT, Goldberg B. Subharmonic imaging of contrast agents. Ultrasonics. 2000;38:93–98.CrossRef Forsberg F, Shi WT, Goldberg B. Subharmonic imaging of contrast agents. Ultrasonics. 2000;38:93–98.CrossRef
26.
go back to reference Forsberg F, Liu J-B, Shi WT, Furuse J, Shimizu M, Goldberg BB. In vivo pressure estimation using subharmonic contrast microbubble signals: proof of concept. IEEE Trans Ultrason Ferroelectr Freq Control. 2005;52:581–583.CrossRef Forsberg F, Liu J-B, Shi WT, Furuse J, Shimizu M, Goldberg BB. In vivo pressure estimation using subharmonic contrast microbubble signals: proof of concept. IEEE Trans Ultrason Ferroelectr Freq Control. 2005;52:581–583.CrossRef
27.
go back to reference Eisenbrey JR, Dave JK, Halldorsdottir VG, et al. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 2013;268:581–588.CrossRef Eisenbrey JR, Dave JK, Halldorsdottir VG, et al. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology. 2013;268:581–588.CrossRef
28.
go back to reference Nam K, Eisenbrey JR, Stanczak M, et al. Monitoring neoadjuvant chemotherapy for Breast cancer by using three-dimensional subharmonic aided pressure estimation and imaging with US contrast agents: preliminary experience. Radiology. 2017;285:53–62.CrossRef Nam K, Eisenbrey JR, Stanczak M, et al. Monitoring neoadjuvant chemotherapy for Breast cancer by using three-dimensional subharmonic aided pressure estimation and imaging with US contrast agents: preliminary experience. Radiology. 2017;285:53–62.CrossRef
29.
go back to reference Gupta I, Eisenbrey JR, Machado P, Stanczak M, Wessner CE, Shaw CM, Gummadi S, Fenkel JM, Tan A, Miller C, Parent J, Schultz S, Soulen MC, Sehgal CM, Wallace K, Forsberg F. Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent. Radiology. 2021 Jan;298:104–111. Gupta I, Eisenbrey JR, Machado P, Stanczak M, Wessner CE, Shaw CM, Gummadi S, Fenkel JM, Tan A, Miller C, Parent J, Schultz S, Soulen MC, Sehgal CM, Wallace K, Forsberg F. Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent. Radiology. 2021 Jan;298:104–111.  
30.
go back to reference Halpern EJ, McCue PA, Aksnes AK, Hagen EK, Frauscher F, Gomella LG. Contrast-enhanced US of the prostate with Sonazoid: comparison with whole-mount prostatectomy specimens in 12 patients. Radiology. 2002;222:361–366.CrossRef Halpern EJ, McCue PA, Aksnes AK, Hagen EK, Frauscher F, Gomella LG. Contrast-enhanced US of the prostate with Sonazoid: comparison with whole-mount prostatectomy specimens in 12 patients. Radiology. 2002;222:361–366.CrossRef
31.
go back to reference Landmark KE, Johansen PW, Johnson JA, Johansen B, Uran S, Skotland T. Pharmacokinetics of perfluorobutane following intravenous bolus injection and continuous infusion of Sonazoid™ in healthy volunteers and in patients with reduced pulmonary diffusing capacity. Ultrasound Med Biol. 2008;34:494–501.CrossRef Landmark KE, Johansen PW, Johnson JA, Johansen B, Uran S, Skotland T. Pharmacokinetics of perfluorobutane following intravenous bolus injection and continuous infusion of Sonazoid™ in healthy volunteers and in patients with reduced pulmonary diffusing capacity. Ultrasound Med Biol. 2008;34:494–501.CrossRef
32.
go back to reference Gupta I, Eisenbrey JR, Machado P, Stanczak M, Wallace K, Forsberg F. On factors affecting subharmonic-aided pressure estimation (SHAPE). Ultrasonic Imaging. 2019;41:35–48.CrossRef Gupta I, Eisenbrey JR, Machado P, Stanczak M, Wallace K, Forsberg F. On factors affecting subharmonic-aided pressure estimation (SHAPE). Ultrasonic Imaging. 2019;41:35–48.CrossRef
33.
go back to reference Gupta I, Nio AQ, Faraci A, et al. The effects of hydrostatic pressure on the subharmonic response of SonoVue and Sonazoid. In 2019 IEEE International Ultrasonics Symposium (IUS), IEEE, 2019, pp 1349–1352. Gupta I, Nio AQ, Faraci A, et al. The effects of hydrostatic pressure on the subharmonic response of SonoVue and Sonazoid. In 2019 IEEE International Ultrasonics Symposium (IUS), IEEE, 2019, pp 1349–1352.
34.
go back to reference Cichoż-lach H, Celiński K, Słomka M, Kasztelan-Szczerbińska B. Pathophysiology of portal hypertension. J Physiol Pharmacol. 2008;59:231–238.PubMed Cichoż-lach H, Celiński K, Słomka M, Kasztelan-Szczerbińska B. Pathophysiology of portal hypertension. J Physiol Pharmacol. 2008;59:231–238.PubMed
35.
go back to reference Iwakiri Y, Groszmann RJ. Pathophysiology of portal hypertension. Variceal hemorrhage. Berlin: Springer; 2014:3–14.CrossRef Iwakiri Y, Groszmann RJ. Pathophysiology of portal hypertension. Variceal hemorrhage. Berlin: Springer; 2014:3–14.CrossRef
Metadata
Title
Hepatic Vein Contrast-Enhanced Ultrasound Subharmonic Imaging Signal as a Screening Test for Portal Hypertension
Authors
Priscilla Machado
Ipshita Gupta
Sriharsha Gummadi
Maria Stanczak
Corinne E. Wessner
Jonathan M. Fenkel
Colette M. Shaw
Susan Shamini-Noori
Susan Schultz
Michael C. Soulen
Chandra M. Sehgal
Kirk Wallace
John R. Eisenbrey
Flemming Forsberg
Publication date
01-12-2021
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 12/2021
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-020-06790-6

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