Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2020; 26(38): 5836-5848
Published online Oct 14, 2020. doi: 10.3748/wjg.v26.i38.5836
Endogenous motion of liver correlates to the severity of portal hypertension
Sigita Gelman, Andrius Sakalauskas, Romanas Zykus, Andrius Pranculis, Rytis Jurkonis, Irma Kuliavienė, Arūnas Lukoševičius, Limas Kupčinskas, Juozas Kupčinskas
Sigita Gelman, Romanas Zykus, Irma Kuliavienė, Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
Andrius Sakalauskas, Rytis Jurkonis, Arūnas Lukoševičius, Biomedical Engineering Institute, Kaunas University of Technology, Kaunas 51423, Lithuania
Andrius Pranculis, Department of Radiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
Limas Kupčinskas, Juozas Kupčinskas, Institute for Digestive Research and Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
Author contributions: Kupcinskas L and Kupcinskas J designed the research; Gelman S, Zykus R and Kuliaviene I treated patients, collected material and clinical data from the patients; Sakalauskas A, Jurkonis R and Lukosevicius A analyzed the radiofrequency signals and developed the algorithm; Pranculis A performed hepatic vein catheterization and HVPG measurement; Gelman S performed ultrasound scanning, analysed the data and drafted the manuscript; Kupcinskas J approved the final version of the manuscript.
Supported by the Research Council of Lithuania, No. S-MIP-19-8; and the Research, Development and Innovation Fund of Kaunas University of Technology, No. MTEPI-L-17003 and MTEPI-L-16012.
Institutional review board statement: The study was reviewed and approved by the Kaunas Region Biomedical Research Ethics Committee (2015-08-24, No. BE-2-28, Kaunas, Lithuania).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: None declared.
Data sharing statement: Technical appendix and dataset available from the corresponding author at sigita.gelman@lsmuni.lt. Informed consent for data sharing was not obtained but the presented data are anonymized, and risk of identification is low.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sigita Gelman, MD, PhD, Assistant Lecturer, Attending Doctor, Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus Str. 9, Kaunas 44307, Lithuania. sigita.gelman@lsmuni.lt
Received: May 21, 2020
Peer-review started: May 21, 2020
First decision: May 29, 2020
Revised: June 11, 2020
Accepted: September 17, 2020
Article in press: September 17, 2020
Published online: October 14, 2020
Processing time: 145 Days and 23.5 Hours
ARTICLE HIGHLIGHTS
Research background

Degree of portal hypertension (PH) is the most important prognostic factor for the decompensation of liver cirrhosis and death, therefore adequate care for patients with liver cirrhosis requires timely detection and evaluation of the presence of clinically significant PH (CSPH) and severe PH (SPH).

Research motivation

As the most accurate method for the assessment of PH is an invasive direct measurement of hepatic venous pressure gradient (HVPG), the search for non-invasive methods to diagnose these conditions is actively ongoing. Ultrasound elastography is one of the most widely used non-invasive alternatives for the diagnosis of PH. Strain elastography (SE) is an ultrasound elastography technique widely used for the examination of musculoskeletal system, breast and thyroid pathologies, however it has been scarcely evaluated in the setting of liver cirrhosis and PH. It is an appealing alternative, as it is considered that SE readings are not affected by hepatic inflammation, jaundice, liver congestion, fatty degeneration, obesity, ascites or narrow intercostal spaces as is the case with other elastography modalities.

Research objectives

Our group has applied SE technique to assess the strain of liver tissue caused by endogenous motion of the beating heart and developed a specific radiofrequency (RF) signal analysis algorithm to calculate the parameters for quantification of strain in liver tissue. The aim of present study was to evaluate the ability and feasibility of endogenously induced displacements and strain on the liver to assess the degree of PH, using this specifically developed RF signal analysis algorithm.

Research methods

Of 36 patients with liver cirrhosis and measured HVPG were included in the case-control study. Endogenous motion of the liver was characterized by derived parameters of region average tissue displacement signal (dantero, dretro, dRMS) and results of endogenous tissue strain imaging using specific radiofrequency signal processing algorithm. Average endogenous strain µ and standard deviation σ of strain were assessed in the regions of interest (ROI) (1 cm × 1 cm and 2 cm × 2 cm in size) and different frequency subbands of endogenous motion (0-10 Hz and 10-20 Hz).

Research results

Four parameters showed statistically significant (P < 0.05) correlation with HVPG measurement. The strongest correlation was obtained for the standard deviation of strain (estimated at 0-10 Hz and 2 cm × 2 cm ROI size). Three parameters showed statistically significant differences between patient groups with CSPH, but only dretro showed significant results in SPH analysis. According to ROC analysis area under the curve (AUC) of the σROI[0…10Hz, 2 cm × 2 cm] parameter reached 0.71 (P = 0.036) for the diagnosis of CSPH; with a cut-off value of 1.28 μm/cm providing 73% sensitivity and 70% specificity. AUC for the diagnosis of CSPH for µROI[0…10Hz, 1 cm × 1 cm] was 0.78 (P = 0.0024); with a cut-off value of 3.92 μm/cm providing 73% sensitivity and 80% specificity. Dretro parameter had an AUC of 0.86 (P = 0.0001) for the diagnosis of CSPH and 0.84 (P = 0.0001) for the diagnosis of SPH. A cut-off value of -132.34 μm yielded 100% sensitivity for both conditions, whereas specificity was 80% and 72% for CSPH and SPH respectively.

Research conclusions

The parameters of endogenously induced displacements and strain of the liver significantly correlated with HVPG. This shows that parameters of endogenous motion could be a potential diagnostic tool for the non-invasive diagnosis of PH. A proposed method is potentially suitable for other applications of non-invasive diagnostics.

Research perspectives

The presented technique has certain limitations. It does not allow the evaluation of strain in real-time differently from commercial SE techniques and the strain parameters are calculated retrospectively, using recorded RF data. The other limitation of the approach is the detection of displacements field only in the direction of ultrasound wave propagation. In this method we have used an undefined endogenous source for the tissue displacement excitation, which might influence quantified evaluation of liver elasticity. Also despite the promising results, this was a pilot study and our results could be biased by the small size of our sample. We are conducting further research of this method, which will include larger groups of patients, also allowing subgroup analysis of patients with ascites and obesity.