The prospective study was approved by the review board of 8th Medical Center of the General Hospital of the Chinese PLA and obtained the written informed consent of all subjects. All methods were carried out in accordance with relevant guidelines and regulations.
Subjects
Between March 2020 and February 2022, a total of 135 subjects with liver disease who were referred by physicians for Gd-EOB-DTPA-enhanced MRI were prospectively enrolled in the study. The Child-Pugh (C-P) grading and renal function (eGFR<30mL·min-1/1.73m²)[29, 30] were obtained within 1 week of the MRI examination. The inclusion criteria were as follows: (1) Gd-EOB-DTPA-enhanced MRI was referred by physicians to clarify hepatic lesions, (2) Older than 18 years, (3) No contraindications to MRI and no allergy to Gd-EOB-DTPA, (4) normal renal function; the exclusion criteria were as follows: (1) Liver without focal lesions,(2) Failure to cooperate with Gd-EOB-DTPA-enhanced MRI, (3) Contrast agent extravasation, (4) Obvious artifacts on HBP imaging, (5) Portal vein embolism, (6) Administration of rifampicin and/or erythromycin during the examination[31, 32].
One hundred and fifteen subjects were enrolled in the final investigation, and 80 of 115 subjects were cirrhotic (type B viral cirrhosis: 65, type C viral cirrhosis: 6, alcoholic cirrhosis: 7, immune hepatitis: 2). Subsequently, 115 patients were divided into four subgroups according to C-P classification [non-cirrhosis subgroup (n=35), C-P A subgroup (n=30), C-P B subgroup (n=35), C-P C subgroup (n=15)]. The flowchart of all subjects was provided in Fig. 1. The final diagnosis of all hepatic focal lesions was based on histopathology after hepatic resection or aspiration biopsy and CT/MRI follow-up[26, 33].
MRI scanning protocol
All subjects underwent Gd-EOB-DTPA-enhanced MRI performed on a 3.0T MRI scanner (Magnetom Skyra, Siemens Healthcare, Erlangen, Germany) in our medical center. Subjects were instructed to fast for 4 hours before the Gd-EOB-DTPA-enhanced MRI, and all subjects were also trained to hold their breath to ensure the quality of HBP imaging before the MRI examination. Subjects were positioned supine with a phased array receiver coil to finish the scanning. The MRI scanning protocol contained location scan, T1WI (in/oppose phase), pre-contrast T1WI three-dimensional Volumetric Interpolated Breath-hold Examination (3D-VIBE), Arterial phase (25 sec), Portal vein phase (65 sec), Transitional phase (2-3 min)[34]. In order to obtain adequate and optimized HBP for all subjects according to the 2016 ESGAR consensus statement for reference standards, we collected 8 HBP at intervals of 5 minutes within 5-40 minutes after intravenous injection. T2-fs-DIXON and EPI-DWI were obtained after HBP[35]. Administration of Gd-EOB-DTPA (Bayer AG, Berlin, Germany, 10 ml, 0.025 mmol/Kg) based on weight was injected at a rate of 2 mL/s via a power injector (Tennessee XD2003, Ulm, Germany) followed by a 20mL saline flush at a rate of 3mL/s. The MRI parameters was shown in Table 1.
Table 1
MRI protocol parameters used in the study
Sequences | Planes | TR (ms) | TE (ms) | FOV (mm) | Slice (mm) | FA | Matrix |
Location | Coronal/Axial/Sagittal | 7.8 | 3.69 | 430 | 6 | 20° | - |
T2 haste bh | Coronal | 1800 | 89 | 380 | 6 | 160° | 256×256 |
T1 in/opp bh | Axial | 166 | 1.23 | 380 | 6 | 70° | 320×180 |
T1 VIBE fs bh (pre-contrast, DCE, HBP) | Axial | 4.06 | 1.89 | 380 | 3 | 9° | 340×274 |
T2-fs-DIXON | Axial | 3000 | 79 | 380 | 6 | 180° | 256×132 |
EPI-DWI (b = 50、800) | Axial | 5600 | 58 | 400 | 6 | 90° | 160×160 |
TR, repetition time; TE, echo time; FOV, field of view; FA, flip angle; bh, breath hold; fs, fat saturate; EPI, echo planar imaging; HBP, Hepatobiliary phase (5, 10, 15, 20, 25, 30, 35, 40 min). |
Collection of adequate HBP
Two radiologists with 9 and 15 years of experience in abdominal MRI assessed independently all subjects’ HBP datasets using 4-point scale (1: poor, 2: insufficient, 3: good, 4: excellent)[36] based to the 2016 ESGAR consensus statement, then the HBP was determined as adequate HBP which be initially rated 3 or 4 points by both radiologists (Fig. 2). Both radiologists were blind with all clinical information of subjects.
Measurement and calculation of LPR
The other two radiologists with 6 and 14 years of experience in abdominal MRI measured the SI of liver and portal vein (SIliver, SIportal vein) using region of interest (ROI) on all adequate HBP respectively. Obvious artifacts, hepatic lesions, blood vessels and bile ducts should be avoided when setting ROI.
The SIliver took the mean SI of forth liver lobes at the hepatic hilar level (ROI=100mm2). SIliver = (SILMlobe + SILLlobe + SIRAlobe + SIRPlobe) / 4.
The SIportal vein was also measured at the hepatic hilar level, and the area of the ROI was determined by the actual size of the portal trunk (Fig. 3). Ultimately, SIliver and SIprotal vein was the mean of ROI measured by two radiologists.
LPR=SIliver / SIportal vein.
Statistical analysis
All statistical analysis was analyzed by SPSS (version 22.0; Chicago, IL USA). The normal distribution of the continuous data was tested by Shapiro-Wilk's test, then normally distributed data were expressed as mean ± standard deviation (Mean ± SD). Spearman rank correlation coefficient was used to analyze the correction between C-P classification and delay time & LPR of adequate HBP. Differences in LPR and delay time of HBP among four subgroups were assessed by one-way ANOVA and Dunnett's multiple comparisons. The reproducibility of measurements was assessed by intraclass correlation coefficient (ICC), and κ-statistics was used to analyze the consistency of the interpretation for HBP adequacy between radiologists, The evaluation of consistency based on κ-value was as follows: 0.01-0.20, poor agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, good agreement; 0.81-0.99, excellent agreement; 1.00, perfect agreement. P value < 0. 05 indicated statistically significant.