Prospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2018; 24(3): 415-423
Published online Jan 21, 2018. doi: 10.3748/wjg.v24.i3.415
Optimization of hepatobiliary phase delay time of Gd-EOB-DTPA-enhanced magnetic resonance imaging for identification of hepatocellular carcinoma in patients with cirrhosis of different degrees of severity
Jian-Wei Wu, Yue-Cheng Yu, Xian-Li Qu, Yan Zhang, Hong Gao
Jian-Wei Wu, Xian-Li Qu, Yan Zhang, Hong Gao, Department of Radiology, Bayi Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, Jiangsu Province, China
Yue-Cheng Yu, Liver Disease Center, Bayi Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, Jiangsu Province, China
Author contributions: Wu JW and Yu YC conceived and wrote the manuscript; Wu JW, Yu YC, Qu XL, Zhang Y and Gao H participated in designing the research, collecting and analyzing the data, and approving the final version.
Institutional review board statement: The study was reviewed and approved by the Academic Committee of Bayi Hospital, Nanjing University of Chinese Medicine.
Informed consent statement: Written informed consent for the GED-MRI scanning was obtained from all the enrolled patients and controls.
Conflict-of-interest statement: All the authors listed above have no potential conflicts of interest relevant to this article to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Yue-Cheng Yu, MD, PhD, Chief Doctor, Professor, Liver Disease Center, Bayi Hospital, Nanjing University of Chinese Medicine, No. 34, Section 34, Yanggongjing, Qinhuai District, Nanjing 210002, Jiangsu Province, China. gslsycy@163.com
Telephone: +86-25-80864059 Fax: +86-25-84586476
Received: October 24, 2017
Peer-review started: October 25, 2017
First decision: November 21, 2017
Revised: December 18, 2017
Accepted: December 26, 2017
Article in press: December 26, 2017
Published online: January 21, 2018
Processing time: 86 Days and 19.2 Hours
ARTICLE HIGHLIGHTS
Research background

Gd-EOB-DTPA-enhanced magnetic resonance imaging (GED-MRI) has significant advantages in finding smaller HCC lesions. However, it is believed that GED-MRI may need remarkably long time for scanning, in which the hepatobiliary phase delay time (HBP-DT) is usually set at 15 to 20 min or longer, and many patients could not cooperate well with the operators during the long process of scanning. Recently, a study reported that DT-10 was sufficient for hepatic lesion characterization in patients with normal liver function and without cirrhosis, and another study concluded that DT-15 was sufficient for patients with mild liver dysfunction classified as cirrhosis of Child-Pugh A (CP-A). However, which HBP-DT is both more efficient and more practical for patients with liver dysfunction that correlates with different degrees of severity of cirrhosis is unknown. Accordingly, we attempted to gather new clinical evidence to optimize the HBP-DT of GED-MRI for detection of HCC in the context of different grades of cirrhosis.

Research motivation

The main topics and key problems of the study include: (1) whether and how the severity of liver cirrhosis will influence the signal intensity of liver parenchyma (LPSI) in the process of GED-MRI examination? (2) whether and how the features of LPSI of liver cirrhosis will interfere with the visibility of HCC? and (3) which HBP-DT will provide the more efficient examination without the discount of diagnostic accuracy in the different context of liver cirrhosis? The findings in the current study will provide first hand information for the answers of above-mentioned questions, and thus contribute to the improvement of rational, efficient, and individual application of GED-MRI.

Research objectives

This study aimed to optimize the HBP-DT of GED-MRI for more efficient identification of HCC occurring in different degrees of cirrhosis assessed by CP score without any discount of diagnostic accuracy. Through the systematic assessment of correlations among liver LPSI, liver parenchyma (LP)/HCC signal ratios, and percentage of visibility of HCC lesions at a series of HBP-DT points in the background of liver cirrhosis with different CP scores, it was demonstrated that the HBP-DT of GED-MRI surely could be optimized in the context of liver cirrhosis with different CP scores. Based on those findings and the existence of heterogeneity in the liver function tests, severity of fibrosis, polymorphism of organic anion transporting polypeptide (OATP), and other potential factors that may interfere with the visibility of HCC, a big-sample multicenter prospective study is needed in the future.

Research methods

This study is a retrospective analysis about how to improve the application of GED-MRI to diagnose HCC occurring in the background of different degrees of cirrhosis. Forty-two patients with HCC from 73 patients with CHB-related cirrhosis were included in this study according to the criteria of inclusion and exclusion. The history and CP scores of CHB-related cirrhosis, the features of LPSI, LP/HCC signal ratios, visibility, and its percentages of HCC lesions at a series of HBP-DT points were systematically collected and compared. The two-way analysis of variance (TW-ANOVA), repeated measures one-way ANOVA (OW-ANOVA), and Huynh-Feldt correction were used to do the statistical analyses of the data. These research methods were the routine ways adopted widely in the clinical investigation.

Research results

The main findings in this study are as follows. First, the LPSI was found to increase time-dependently both in healthy controls and in patients with HCC overlapped on cirrhosis. Second, the LP/HCC signal ratios had a significant difference among various HBP-DT points, as well as between the CP-A and CP-B/C subgroups. Third, the constituent ratios of HCC foci identified as obvious hypointensity (+++), moderate hypointensity (++), and mild hypointensity/isointensity (+/-) kept stable from DT-10 to DT-25 in each subgroups, but had a difference among subgroups with cirrhosis of CP-A, CP-B, or CP-C. To our knowledge, this is the first time to report that HCC visibility at DT-10 is equal to that at DT-15 or longer DT; that is, compared to longer DT, DT-10 had the same diagnostic accuracy, but showed more efficient diagnosis of HCC existing in the background of both CP-A cirrhosis and CP-B cirrhosis. The problems that remain to be solved in the future include: (1) whether DT-10 will still keep the same high efficiency and accuracy for identification of HCC overlapped on CP-A and CP-B cirrhosis when this concept is applied to more patients; (2) whether and what kind of OATP polymorphism will interfere with the diagnostic efficacy of GED-MRI when used for identification of HCC in Chinese patients; and (3) how to improve the detection of HCC lesions presenting as mild hypointensity or even isointensity in patients with CP-C cirrhosis.

Research conclusions

The conclusions from this study are summarized as follows. First, the severity of liver cirrhosis has significant negative influence on the HCC visualization by GED-MRI. Second, DT-10 is more efficient and practical than other HBP-DT points to identify most of HCC foci emerging in CP-A cirrhosis, as well as in CP-B cirrhosis. This is the most important new finding of this study. Third, an HBP-DT of 15 min or longer seems more appropriate than DT-10 for visualization of HCC in patients with CP-C cirrhosis. Based on the new findings of this study, we proposed that DT-10 should be chosen as the most appropriate HBP-DT point of GED-MRI for most of the patients with HCC overlapped on CP-A and CP-B cirrhosis, but a longer DT should be used for patients with CP-C patients.

Research perspectives

This study told clinicians that the status of liver cirrhosis should be assessed carefully before GED-MRI examination in order to choose the most efficient HBP-DT point without any discount of accuracy which is based on the visibility of HCC lesions. It was shown in this study that DT-10 was the optimal HBP-DT which could satisfy the requirement of HCC diagnosis in most of the patients suffering from both CP-A/B liver cirrhosis and HCC, without the necessity of longer HBP-DT. On the other hand, a longer HBP-DT ≥ 15 min might improve the visibility of some HCCs overlapped on CP-C cirrhosis. These interesting findings need to be further confirmed in more patients in the future, and the best method to attain this objective is well-designed multicenter big-sample prospective study.