Assessment of hepatic transporter function in rats using dynamic gadoxetate-enhanced MRI: a reproducibility study.

OBJECTIVE: Previous studies have revealed a substantial between-centre variability in DCE-MRI biomarkers of hepatocellular function in rats. This study aims to identify the main sources of variability by comparing data measured at different centres and field strengths, at different days in the same subjects, and over the course of several months in the same centre. MATERIALS AND METHODS: 13 substudies were conducted across three facilities on two 4.7 T and two 7 T scanners using a 3D spoiled gradient echo acquisition. All substudies included 3-6 male Wistar-Han rats each, either scanned once with vehicle (n = 76) or twice with either vehicle (n = 19) or 10 mg/kg of rifampicin (n = 13) at follow-up. Absolute values, between-centre reproducibility, within-subject repeatability, detection limits, and effect sizes were derived for hepatocellular uptake rate (Ktrans) and biliary excretion rate (kbh). Sources of variability were identified using analysis of variance and stratification by centre, field strength, and time period. RESULTS: Data showed significant differences between substudies of 31% for Ktrans (p = 0.013) and 43% for kbh (p < 0.001). Within-subject differences were substantially smaller for kbh (8%) but less so for Ktrans (25%). Rifampicin-induced inhibition was safely above the detection limits, with an effect size of 75 ± 3% in Ktrans and 67 ± 8% in kbh. Most of the variability in individual data was accounted for by between-subject (Ktrans = 23.5%; kbh = 42.5%) and between-centre (Ktrans = 44.9%; kbh = 50.9%) variability, substantially more than the between-day variation (Ktrans = 0.1%; kbh = 5.6%). Significant differences in kbh were found between field strengths at the same centre, between centres at the same field strength, and between repeat experiments over 2 months apart in the same centre. DISCUSSION: Between-centre bias caused by factors such as hardware differences, subject preparations, and operator dependence is the main source of variability in DCE-MRI of liver function in rats, closely followed by biological between-subject differences. Future method development should focus on reducing these sources of error to minimise the sample sizes needed to detect more subtle levels of inhibition.

Clear cell hepatocellular carcinoma: Gd-EOB-DTPA-enhanced MR imaging features and prognosis.

PURPOSE: To investigate imaging findings on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and prognosis of clear cell hepatocellular carcinoma (CCHCC) comparing with non-otherwise specified hepatocellular carcinoma (NOS-HCC). METHODS: The clinical, pathological and MR imaging features of 42 patients with CCHCC and 84 age-matched patients with NOS-HCC were retrospectively analyzed from January 2015 to October 2021. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors for CCHCC. Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier analysis. RESULTS: CCHCC showed fat content more frequently (P < 0.001) and relatively higher Edmondson tumor grade (P = 0.001) compared with NOS-HCC. The lesion-to-muscle ratio (LMR) and lesion-to-liver ratio (LLR) of CCHCC on pre-enhancement T1-weighted imaging (pre-T1WI) (P = 0.001, P = 0.003) and hepatobiliary phase (HBP) (P = 0.007, P = 0.048) were significantly higher than those of NOS-HCC. The area under the curve (AUC) for fat content, LLR on pre-T1WI and their combination with better diagnostic performance in predicting CCHCC were 0.678, 0.666, and 0.750, respectively. There was no statistically significant difference in clinical outcomes between CCHCC and NOS-HCC. Multivariate Cox analysis confirmed that tumor size > 2 cm and enhancing capsule were independent prognostic factors for DFS and OS among CCHCC patients. CONCLUSION: Fat content and adjusted lesion signal intensity on pre-T1WI and HBP could be used to differentiate CCHCC from NOS-HCC. CCHCC had similar prognosis with NOS-HCC.

Based on Gadolinium Ethoxybenzyl DTPA-Enhanced MRI: Diagnostic Performance of the Category-Modified LR-5 Criteria in Patients At Risk for Hepatocellular Carcinoma.

Introduction: We aimed to modify the LR-5 strategy to improve the diagnostic sensitivity for hepatocellular carcinoma (HCC) in high-risk patients while maintaining specificity. Methods: This study retrospectively analyzed 412 patients with 445 liver observations who underwent preoperative gadolinium ethoxybenzyl DTPA (GD-EOB-DTPA)-enhanced MRI followed by surgical procedures or biopsies. All observations were classified according to LI-RADS v2018, and the classifications were adjusted by modifying major features (MF)(substituting threshold growth with a more HCC-specific ancillary features (AF): presence of blood products within the mass, arterial phase hyperenhancement (APHE) was interpreted with hypointensity on precontrast imaging- isointensity in arterial phase (AP) and extending washout to transitional phase (TP)(2 min)). The specificity, sensitivity, and positive predictive value (PPV) were assessed to compare LR-5 (definitely HCC) diagnostic efficacy between LI-RADS version 2018 and modified LI-RADS. Results: Apart from nonenhancing "capsule", the interreader agreement of MFs and HCC-specific AFs between the two readers reached substantial or excellent ranges (κ values ranging from 0.631 to 0.911). According to LI-5 v2018, the specificity, sensitivity and PPV of HCC were 90.74%, 82.35%, and 98.17%, respectively. Based on a more HCC-specific AF, signal intensity in AP and TP (2 min), the sensitivity of the three modified strategies were 86.19%, 93.09%, 96.67% (P < .05)), while maintaining high specificity and PPV rates at 88.89% and 98.25% (P > .05) Conclusion: Further investigation into the efficacy of threshold growth as a MF is warranted. By utilizing GD-EOB-DTPA-enhanced MRI, enhancing the sensitivity of the modified LR-5 category may be achieved without compromising specificity and PPV in diagnosing HCC among high-risk patients.

Assessing regional hepatic function changes after hypertrophy induction by radioembolisation: comparison of gadoxetic acid-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy.

BACKGROUND: To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies. METHODS: Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL). RESULTS: Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046). CONCLUSION: LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE. RELEVANCE STATEMENT: MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction. KEY POINTS: • Both MRI and HBS can assess liver function after RE. • Liver enhancement on MRI correlates with mebrofenin uptake on HBS. • MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction.