Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 27, 2022; 14(7): 1459-1469
Published online Jul 27, 2022. doi: 10.4254/wjh.v14.i7.1459
Hepatobiliary phases in magnetic resonance imaging using liver-specific contrast for focal lesions in clinical practice
Daniel Alvarenga Fernandes, Eduardo Andreazza Dal Lago, Felipe Aguera Oliver, Bruna Melo Coelho Loureiro, Daniel Lahan Martins, Thiago José Penachim, Ricardo Hoelz de Oliveira Barros, José de Arimatéia Batista Araújo Filho, Larissa Bastos Eloy da Costa, Áurea Maria Oliveira da Silva, Elaine Cristina de Ataíde, Ilka de Fátima Santana Ferreira Boin, Nelson Marcio Gomes Caserta
Daniel Alvarenga Fernandes, Eduardo Andreazza Dal Lago, Daniel Lahan Martins, Thiago José Penachim, Ricardo Hoelz de Oliveira Barros, Nelson Marcio Gomes Caserta, Department of Radiology, School of Medical Sciences, University of Campinas- UNICAMP, Campinas 13083-888, São Paulo, Brazil
Felipe Aguera Oliver, Department of Radiology, Medical School, São Paulo State University- UNESP, Botucatu 18618-970, São Paulo, Brazil
Bruna Melo Coelho Loureiro, Instituto de Radiologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo- InRad/HC-FMUSP, São Paulo 05403-010, SP, Brazil
José de Arimatéia Batista Araújo Filho, Department of Radiology, Sírio- Libanês Hospital, São Paulo 05652-900, SP, Brazil
Larissa Bastos Eloy da Costa, Department of Pathology, School of Medical Sciences, University of Campinas - UNICAMP, Campinas 13083-888, São Paulo, Brazil
Áurea Maria Oliveira da Silva, Elaine Cristina de Ataíde, Ilka de Fátima Santana Ferreira Boin, Liver Transplant Unit, Department of Surgery, School of Medical Sciences, University of Campinas- UNICAMP, Campinas 13083-888, São Paulo, Brazil
Author contributions: Fernandes DA, Caserta NMG, and Boin IFFS designed the research study; Fernandes DA, Dal Lago EA, Oliver FA, and Loureiro BMC performed the research; Dal Lago EA, Oliver FA, Martins DL, Penachim TJ, Barros RHO, and Araújo-Filho JAB contributed analytic tools and analyzed the data; and All authors have read and approved the final manuscript.
Institutional review board statement: Project approved by the Institutional Research Ethics Committee, UNICAMP, opinion number 962.639, CAAE: 41531415.0.0000.5404. Identification of the study under the Universal Trial Number (UTN): U1111-1247-9655.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Data sharing statement: Dataset available from the corresponding author at daniel_alvafer@yahoo.com.br. The presented data are anonymized and risk of identification is low.
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE Statement.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Daniel Alvarenga Fernandes, Doctor, Medical Assistant, Research Associate, Department of Radiology, School of Medical Sciences, University of Campinas- UNICAMP, Rua Vital Brasil, 251, Cidade Universitária, Campinas 13083-888, São Paulo, Brazil. daniel_alvafer@yahoo.com.br
Received: February 23, 2022
Peer-review started: February 23, 2022
First decision: April 17, 2022
Revised: April 20, 2022
Accepted: July 11, 2022
Article in press: July 11, 2022
Published online: July 27, 2022
Processing time: 153 Days and 21.1 Hours
ARTICLE HIGHLIGHTS
Research background

The accurate characterization of focal liver lesions (FLL) has great clinical relevance. Although ultrasonography (US) and computed tomography (CT) are the most important diagnostic tools for screening FLL, magnetic resonance imaging (MRI) is a well-established diagnostic imaging method in clinical practice and produces images without ionizing radiation, with good spatial resolution and excellent tissue resolution, thus allowing a very reliable assessment. One of the main innovative trends currently, is the use of molecular and functional methods.

Research motivation

Challenging lesions, difficult to diagnose through non-invasive methods, constitute an important emotional burden for each patient regarding a still uncertain diagnosis (malignant x benign). In addition, from a therapeutic and prognostic point of view, delay in a definitive diagnosis can lead to worse outcomes. Numerous liver-specific contrast agents have been developed and studied in recent years to improve the performance of liver MRI. More recently, one of the contrast agents introduced in clinical practice is gadoxetic acid (gadoxetate disodium).

Research objectives

To determine the value of hepatobiliary phases (HBP) using gadoxetic acid as a liver-specific agent in MRI in addition to the non-contrast and dynamic phases after contrast in the characterization of benign and malignant FLL in clinical practice, including hepatocellular carcinoma and metastases.

Research methods

Controlled diagnostic clinical trial. Two radiologists independently assessed the four stages of images in the following order: Stage 1: Non-contrast images (T1-pre-contrast; T2-weighted images with and without fat saturation; DWI, b-value 1000); Stage 2: Non-contrast images and dynamic phases following injection of gadoxetic acid (arterial, portal, and transitional phase); Stage 3: Addition of hepatobiliary phase ten minutes (HBP10’) following the injection of gadoxetic acid in stage 2; Stage 4: Addition of hepatobiliary phase twenty minutes (HBP 20’) following the injection of gadoxetic acid in stage 2. A 6-point scale was created by the author for the assessment of each focal liver lesion in each stage. The method of Generalized Estimating Equations (GEE) was used to compare the stages. The estimates were calculated by maximum likelihood to weight the difference in the number of repetitions for each patient. The receiver operating characteristic (ROC) curve for repeated measurements was used to assess the accuracy of each stage in relation to the definitive diagnosis.

Research results

The interobserver agreement was high (weighted Kappa coefficient: 0.81-1) at all stages in the characterization of benign and malignant FLL. The diagnostic weighted accuracy (Az) was 0.80 in stage 1 and was increased to 0.90 in stage 2. Addition of the hepatobiliary phase increased Az to 0.98 in stage 3, which was also 0.98 in stage 4.

Research conclusions

The value of morphofunctional MRI with gadoxetic acid as a liver-specific contrast in addition to the usual dynamic phases after contrast medium (arterial, portal and transitional/equilibrium) was to increase the proportion of hits for differentiation between benign and malignant FLL in relation to the definitive diagnosis.

Research perspectives

With growing potential in the era of precision medicine, the improvement and dissemination of the method among medical field can bring benefits in the management of patients with focal liver lesions that are difficult to diagnose. With the accumulation of experience, the use demonstrated herein and other potentials of morphofunctional MRI with liver-specific contrast as a new potential imaging tumor biomarker may be established, benefiting patients with challenging focal liver lesions. Other potential benefits in living laboratories have brought to light new uses of this methodology, such as outcome predictions and co-creation intelligences for the resolution and/or amelioration of specific diseases to patients, emerging as promising prospects. Further potential liver-specific contrast applications include assesment of liver fibrosis, the evaluation of the functional hepatic reserve before partial hepatectomy; evaluation of live donor's hepatic function as well as evaluation of early liver failure after transplantation. In another active area of ​​investigation, morphofunctional MRI with liver-specific contrast may provide a system for stratifying patients according to risk of recurrence with a likely influence on the outcomes of locoregional HCC treatments. Also new translational studies similar to this one in other parts of the world added to the socioeconomic background and specificities of each region may bring benefits to this group of patients.