Extracellular contrast agent-enhanced MRI is as effective as gadoxetate disodium-enhanced MRI for predicting microvascular invasion in HCC.

PURPOSE: To compare the performances of gadoxetate disodium-enhanced MRI (EOB-MRI) and extracellular contrast agent-enhanced MRI (ECA-MRI) for predicting microvascular invasion (MVI) in HCC. MATERIALS AND METHODS: From November 2009 to December 2021, consecutive HCC patients who underwent preoperative contrast-enhanced MRI were retrospectively enrolled into either an ECA-MRI or EOB-MRI cohort. In the ECA-MRI cohort, a preoperative MVI score was constructed in the training dataset using a logistic regression model that evaluated pathological type. In a propensity score-matched testing dataset of the ECA-MRI cohort, the MVI score was validated and compared with a previously proposed EOB-MRI-based MVI score calculated in the EOB-MRI cohort. Time-to-early recurrence survival was evaluated by the Kaplan-Meier method with the log-rank test. RESULTS: A total of 536 patients were included (478 men; 53 years, interquartile range, 46-62 years), 322 (60.1 %) with pathologically confirmed MVI. Based on the training dataset, independent variables associated with MVI included serum alpha-fetoprotein > 400 ng/ml (odds ratio [OR] = 2.3), infiltrative appearance (OR = 4.9), internal artery (OR = 2.5) and nodule-in-nodule architecture (OR = 2.4), which were incorporated into the ECA-MRI-based MVI score. The testing dataset AUC of the ECA-MRI score was 0.720, which was comparable to that of the EOB-MRI-based MVI score (AUC = 0.721; P =.99). Patients from either the ECA-MRI or the EOB-MRI cohort with model-predicted MVI had significantly shorter time-to-early recurrence than those without MVI (P <.001). CONCLUSION: Based on the preoperative serum alpha-fetoprotein and three MRI features, ECA-MRI demonstrated comparable performance to EOB-MRI for predicting MVI in HCC.

The diagnostic performance of contrast-enhanced CT versus extracellular contrast agent-enhanced MRI in detecting hepatocellular carcinoma: direct comparison and a meta-analysis.

To compare the diagnostic value of contrast-enhanced computed tomography (CT) with extracellular contrast agent-enhanced magnetic resonance imaging (ECA-MRI) for the detection of hepatocellular carcinoma (HCC). Pubmed, Embase, Web of Science and Cochrane Library were searched (1/5/2021) for studies comparing contrast-enhanced CT with ECA-MRI in patients suspected of HCC. Studies without head-to-head comparison were excluded. The pooled sensitivity, specificity and summary area under the curve (sAUC) of contrast-enhanced CT and ECA-MRI in detecting HCC was calculated based on bivariate random effects model. Heterogeneity test included threshold effect analysis and meta-regression. Subgroup analyses were conducted according to lesion size (< 20 mm or ≥ 20 mm). Overall, 10 articles containing 1333 patients were deemed suitable for inclusion in this meta-analysis. ECA-MRI displayed increased sensitivity to contrast-enhanced CT in detecting HCC (0.77 vs. 0.63, P < 0.01). The difference in specificity between ECA-MRI and contrast-enhanced CT was not statistically significant (0.93 vs. 0.94, P = 0.25). ECA-MRI yielded higher diagnostic accuracy (sAUCs = 0.88 vs. 0.80, P < 0.01). In the subgroup analysis with a lesion size < 20 mm, ECA-MRI allowed significant gains of accuracy compared to contrast-enhanced CT (0.79 vs. 0.72, P = 0.02). ECA-MRI also outperformed contrast-enhanced CT in patients with lesion size ≥ 20 mm (sAUCs = 0.96 vs. 0.93, P = 0.04). ECA-MRI provided higher sensitivity and accuracy than contrast-enhanced CT in detecting HCC, especially lesions size < 20 mm.

Update on MR Contrast Agents for Liver Imaging: What to Use and When.

Contrast-enhanced liver MR imaging is an important diagnostic tool for many different liver diseases with the sensitivity and specificity in diagnosing liver diseases typically far exceeding other imaging modalities. The safety profile of GBCA is excellent with minimal adverse events. Both extracellular and hepatobiliary contrast agents offer unique advantages and potential limitations. ECA is excellent for obtaining high-quality arterial phase imaging and can be particularly useful for the evaluation of hepatocellular carcinoma (HCC) in cirrhotic patients. In contrast, hepatobiliary agent (HBA) can help distinguish FNH from adenomas, detect liver metastases, and provide biliary imaging due to their uptake within normal hepatocytes and biliary excretion.

Enhancing capsule in hepatocellular carcinoma: intra-individual comparison between CT and MRI with extracellular contrast agent.

PURPOSE: The purpose of this study was to compare the value of contrast-enhanced computed tomography (CT) to that of magnetic resonance imaging obtained with extracellular contrast agent (ECA-MRI) for the diagnosis of a tumor capsule in hepatocellular carcinoma (HCC) using histopathologic findings as the standard of reference. MATERIALS AND METHODS: This retrospective study included patients with pathologically-proven resected HCCs with available preoperative contrast-enhanced CT and ECA-MRI examinations. Two blinded radiologists independently reviewed contrast-enhanced CT and ECA-MRI examinations to assess the presence of an enhancing capsule. The histopathological analysis of resected specimens was used as reference for the diagnosis of a tumor capsule. The sensitivity and specificity of CT and ECA-MRI for the diagnosis of a tumor capsule were determined, and an intra-individual comparison of imaging modalities was performed using McNemar test. Inter-reader agreement was assessed using Kappa test. RESULTS: The study population included 199 patients (157 men, 42 women; mean age: 61.3 ± 13.0 [SD] years) with 210 HCCs (mean size 56.7 ± 43.7 [SD] mm). A tumor capsule was present in 157/210 (74.8%) HCCs at histopathologic analysis. Capsule enhancement was more frequently visualized on ECA-MRI (R1, 68.6%; R2, 71.9%) than on CT (R1, 44.3%, P < 0.001; R2, 47.6%, P < 0.001). The sensitivity of ECA-MRI was better for the diagnosis of histopathological tumor capsule (R1, 76.4%; R2, 79.6%; P < 0.001), while CT had a greater specificity (R1, 84.9%; R2, 83.0%; P < 0.001). Inter-reader agreement was moderate both on CT (kappa = 0.55; 95% confidence interval [CI]: 0.43-0.66) and ECA-MRI (kappa = 0.57; 95% CI: 0.45-0.70). CONCLUSION: Capsule enhancement was more frequently visualized on ECA-MRI than on CT. The sensitivity of ECA-MRI was greater than that of CT, but the specificity of CT was better than that of ECA-MRI.

Assessing locoregional treatment response to Hepatocellular Carcinoma: comparison of hepatobiliary contrast agents to extracellular contrast agents.

Cross-sectional imaging with contrast-enhanced magnetic resonance imaging (MRI) is routinely performed in patients with hepatocellular carcinoma (HCC) to assess tumor response to locoregional therapy (LRT). Current response assessment algorithms, such as the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (TRA), allow assessment using conventional gadolinium-based extracellular contrast agents (ECA) for accurate tumor response assessment following LRT. MRI with hepatobiliary agents (HBA) allows an acquisition of hepatobiliary phase (HBP), which is proven to increase sensitivity for detection of observations in at-risk patients, particularly for findings < 2 cm. The use of HBA is not yet incorporated into the TRA; however, it is increasingly used in clinical practice. Few published studies have evaluated the performance of LI-RADS TRA by applying ancillary features related to HBP that has resulted in category adjustment, enabling more sensitive and unequivocal diagnosis. This may help timely management of viable cases, without a significant loss of specificity in comparison with the ECA-based LI-RADS TRA assessment. In this review, we will describe and compare the imaging appearance of treated HCC on MRI using extracellular and hepatobiliary contrast agents and discuss emerging evidence and pitfalls in the assessment of tumor response following LRT with HBA.

Dual contrast liver MRI: a pictorial illustration.

Liver magnetic resonance imaging (MRI) is a commonly performed imaging technique with multiple indications and applications. There are two general groups of contrast agents used when imaging the liver, extracellular contrast agents (ECA) and hepatobiliary agents (HBA), each of which has its own advantages and limitations. Liver MRI with ECA provides excellent information on abdominal vasculature and better quality multi-phasic studies for characterization of focal liver lesions. HBA improves lesion detection, provides information regarding liver function and can be helpful for evaluating biliary tree anatomy, excretion, anastomotic stenoses, or leaks. Most liver MRI studies are usually performed with one agent, however in some cases, a second study is performed with another agent to obtain additional information or confirm the findings in the first study. Administering both agents in a single exam can potentially eliminate the need for additional imaging in certain situations. In this pictorial review, the techniques and indications for dual contrast MRI will be detailed with multiple demonstrative examples.

Diagnostic performance of MRI for HCC according to contrast agent type: a systematic review and meta-analysis.

BACKGROUND/PURPOSE: Conflicting results have been reported between the use of extracellular contrast agent (ECA) and hepatobiliary contrast agent (HBA) when magnetic resonance imaging (MRI) is used for the diagnosis of hepatocellular carcinoma (HCC). Therefore, we aimed to compare the diagnostic performance of MRI using ECA (ECA-MRI) and HBA (HBA-MRI). METHODS: Original studies reporting the diagnostic performance of contrast-enhanced MRI for the diagnosis of HCC published between January 2010 and February 2020 were identified in a Pubmed, EMBASE, and Cochrane Library database search. The pooled sensitivity and specificity of ECA-MRI and HBA-MRI were calculated using a bivariate random effects model and compared using a joint-model bivariate meta-regression. Subgroup analyses were performed to compare the diagnostic performance of ECA-MRI and HBA-MRI according to study design, underlying liver disease, lesion size, reference standard, and imaging criteria. RESULTS: Of the 1760 screened articles, 31 studies were included: 15 studies included 2890 lesions imaged using ECA-MRI and 19 studies included 3893 lesions imaged using HBA-MRI. The pooled sensitivity and specificity were not significantly different between ECA-MRI (sensitivity, 72% [95% confidence interval 65-79%]; specificity 92% [89-95%]) and HBA-MRI (76% [68-83%]; 92% [87-95%], p = 0.72). Subgroup analyses did not find differences in diagnostic performance between ECA-MRI and HBA-MRI according to study design (p ≥ 0.11), underlying disease (p ≥ 0.09), lesion size (≤ 2 cm, p = 0.97), reference standard (p = 0.70), or imaging criteria (p = 0.33). CONCLUSION: ECA-MRI showed similar performance to HBA-MRI in the diagnosis of HCC. The contrast agent might be selected with consideration of the advantages of each agent.

Gastroenteropancreatic neuroendocrine tumors: impact of consistent contrast agent selection on radiologists' confidence in hepatic lesion assessment on restaging MRIs.

PURPOSE: To evaluate the impact of contrast agent selection on radiologists' confidence in assessing liver lesions on follow-up magnetic resonance imaging (MRI) studies in patients with neuroendocrine tumors. METHODS: This Institutional Review Board-approved, retrospective study performed at a tertiary cancer center and a quaternary care urban academic hospital included all 694 follow-up abdominal MRI studies from 179 patients with gastroenteropancreatic neuroendocrine tumor performed from 01/01/2010 to 05/31/2015. Primary outcome measure was radiologists' confidence in assessing liver lesions on follow-up MRI. MRI reports were reviewed to abstract radiologists' confidence, classified as "equivocal" if any equivocal connotation (mention of limitation due to differences in contrast agent or follow-up recommendation with specific contrast agent) was present; or "unequivocal" if a precise, confident comparison to prior was documented without the use of ambiguous terms. A fellowship-trained radiologist separately evaluated 100 randomly selected reports and images to calculate interobserver agreement with the report classification (equivocal vs. unequivocal) and with the original MRI report, respectively. Chi-square test was used to compare the proportion of equivocal reports when "same" or "different" contrast agent was used for successive examinations. RESULTS: Rates of equivocal reports were higher when different contrast agents were used for successive examinations compared to examinations with same contrast agent (13.2% [21/159] vs. 1.8% [10/535]; p < 0.0001). There was very good interobserver agreement for assessment of radiologist confidence (κ = 0.92 for report review, κ = 0.82 for image review). CONCLUSIONS: Consistent use of contrast agent for follow-up MRIs allows more confident assessment of liver lesions in patients with neuroendocrine tumors.

Leakage and water exchange characterization of gadofosveset in the myocardium.

PURPOSE: To determine the compartmentalization of the blood pool agent gadofosveset and the effect of its transient binding to albumin on the quantification of steady-state fractional myocardial blood volume (fMBV). METHODS: Myocardial vascular fraction measurements were simulated assuming the limiting cases (slow or fast) of two-compartment water exchange for different contrast agent injection concentrations, binding fractions, bound and free relaxivities, and true cardiac vascular fractions. fMBV was measured in five healthy volunteers (4 males, 1 female, average age 33) at 1.5T after administration of five injections of gadofosveset. The measurements in the volunteers were retrospectively compared to measurements of fMBV after three serial injections of the ultra-small, paramagnetic iron oxide (USPIO) blood pool agent ferumoxytol in an experimental animal. The true fMBV and exchange rate of water protons in both human and animal data sets was determined by chi square minimization. RESULTS: Simulations showed an error in the measurement of fMBV due to partial binding of gadofosveset of less than 30%. Measured fMBV values over-estimate simulation predictions, and approach cardiac extracellular volume (22%), which suggests that the intravascular assumption may not be appropriate for the myocardium, although it may apply to more distal perfusion beds. In comparison, fMBV measured with ferumoxytol (5%, with slow water proton exchange across vascular wall) agree with published values of myocardial vascular fraction. Further comparison between myocardium relaxation rates induced by gadofosveset and by other extracellular and intravascular contrast agents showed that gadofosveset behaves like an extracellular contrast agent. CONCLUSIONS: The distribution of the volunteer data indicates that a three-compartment model, with slow water exchange of gadofosveset and water protons between the vascular and interstitial compartments, and fast water exchange between the interstitium and the myocytes, is appropriate. The ferumoxytol measurements indicate that this USPIO is an intravascular contrast agent that can be used to quantify myocardial blood volume, with the appropriate correction for water exchange using a two-compartment water exchange model.