This study was approved by the Institutional Review Board of Zhongshan Hospital, Fudan University (approval number B2018-236) in accordance with the ethical guidelines of the Declaration of Helsinki. The committee waived the requirement for informed consent because it is a retrospective study.
Patients selection
According to the AASLD guideline, patients with preexisting cirrhosis were at high risk for developing HCC and surveillance program of ultrasound (US) and a-fetoprotein (AFP) were recommended. In our institution, between February 2016 and March 2017, 222 patients underwent gadoxetic acid-enhanced MRI for further evaluation of suspicious HCCs detected during surveillance. Patients with probable benign nodules (i.e., cysts, hemangiomas, arterioportal shunts) screened by US or patients with HCCs having any previous treatments such as transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) were initially excluded from the study. The inclusive criteria of the patient selection were: (a) single HCC with histology and preoperative gadoxetic acid-enhanced MRI; (b) the interval time between MRI protocol and the operation was less than 2 weeks; (c) patients in Child-Pugh A-B; (d) HCC with qualified MR images. Of the 222 patients, 55 patients were excluded for having two or more HCCs; 8 patients were excluded for Child-Pugh C; 28 were excluded for other types of nodules including intrahepatic cholangiocarcinoma (n = 15), combined HCC and cholangiocarcinoma (n = 1), dysplastic nodule (n = 10) and metastasize (n = 2); 16 patients were excluded for more than 2 weeks interval time during follow-up; 21 patients were excluded for lesions on left lobe with susceptibility or respiratory motion artifacts on DW images. Finally, 94 patients with single HCC were included in our study (Fig. 1).
MR Imaging Protocol
All patients enrolled in our study underwent gadoxetic acid-enhanced MRI in a single 1.5-T MR system (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany), with a 8-channel phased-array receiver coil. Single-spin echo plane DWI for free breathing (3200/56 milliseconds repetition time (TR) / echo time (TE), 84 × 128 matrix, 380–400 × 300–324 mm field of view (FOV), 5.5 mm slice thickness) was performed, and corresponding ADC maps were automatically generated with b values of 0 and 500 s/mm2. Dynamic contrast-enhanced T1-weighted 3D gradient-recalled echo images (3.47 / 1.36 TR / TE, 320 × 195 matrix, 10° flip angle, 308 × 380 mm FOV, 3 mm slice thickness) were obtained after intravenously injection of contrast agent. A dual flip-angle (Flip angle, 2° and 12°) before and at 20 min after injection of gadoxetic acid based on a voxel-by-voxel basis was applied for generating T1 maps with syngo MapIt. The precontrast phase was obtained before a bolus injection of 0.025 mmol/kg of gadoxetic acid (Primovist, Bayer Schering Pharma, Berlin, Germany) at a rate of 1 ml/sec with a subsequent 20 ml saline flush. Subsequent MR images during the arterial phase (automatically triggered when the ascending aorta reached peak enhancement), the portal vein phase (about 14 seconds), the transition phase (about 3 minutes), and the hepatobiliary phase (HBP; 20 minutes) were obtained.
MR images analysis
Two abdominal radiologists (Blinded) independently reviewed the MR images of all the patients. Region of interest (ROI) was outlined around the edge of tumor on each slice on precontrast T1 maps, postcontrast T1 maps and ADC maps, which were copied from ROIs of HCCs that drawn on high flip angle (12°) T1-weighted images and high b value images (500 s/mm2), respectively (Fig. 2). Precontrast, postcontrast T1 relaxation time and ADC values of the two observers were then calculated. We also calculated the reduction rate (Δ%) of T1 relaxation time using the following formula: Δ%= 100% × (pre T1 value − post T1 value) / pre T1 value, in which pre T1 and post T1 values representing the T1 relaxation times before and after injection of gadoxetic acid.
Reference standard for MVI
Pathological data including presence of cirrhosis, Edmondson-Steiner grade or microvascular invasion was according to surgical pathologic reports generated by our institutional pathologists specialized in liver histology (each individual with more than 20 years of experience). Microvascular invasion was defined as presence of muscular wall in any vascular space with invasion or adherence of any intravascular tumors to the vessel wall visible microscopically.
Statistical Analysis
Frequencies of categorical variables for differentiating MVI were co mpared by using Fisher exact test. Difference of quantitative variables including precontrast/postcontrast T1 relaxation time and ADC values between MVI-positive and MVI-negative groups was compared by using independent sample t test. The interclass correlation coefficient (ICC) of quantitative data between the two observers was calculated (poor: <0.40; fair: 0.40–059; good: 0.60–0.74; excellent: 0.75-1.00). Area under receiver operating characteristic curve (AUC) with 95% confidence interval (95% CI) based on receiver operating characteristic curve (ROC) analysis was generated for evaluating the utility of variables to discriminate the status of MVI. Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratio (LR) of appropriate cutoff value corresponding to maximal Youden index by using ROC analysis were presented with 95% CI. All the statistical tests were performed by using statistical software (SPSS version 21, SPSS, Chicago, III) and a two-side P value less than 0.05 indicating significance level.