Extracellular Contrast Agent Research Articles

Diagnostic performance of the 2022 KLCA-NCC criteria for hepatocellular carcinoma on magnetic resonance imaging with extracellular contrast and hepatobiliary agents: comparison with the 2018 KLCA-NCC criteria.

This study aimed to determine the diagnostic performance of 2022 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) imaging criteria compared with the 2018 KLCA-NCC for hepatocellular carcinoma (HCC) in high-risk patients using magnetic resonance imaging (MRI). This retrospective study included 415 treatment-naïve patients (152 patients who underwent extracellular contrast agent [ECA]-MRI and 263 who underwent hepatobiliary agent [HBA]-MRI; 535 lesions, including 412 HCCs) with a high risk of HCC who underwent contrast-enhanced MRI. Two readers evaluated all lesions according to the 2018 and 2022 KLCA-NCC imaging diagnostic criteria, and the per-lesion diagnostic performances were compared. In "definite" HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI showed a significantly higher sensitivity for the diagnosis of HCC than ECA-MRI (77.0% vs. 64.3%, P=0.006) without a significant difference in specificity (94.7% vs. 95.7%, P=0.801). On ECAMRI, "definite" or "probable" HCC categories of the 2022 KLCA-NCC had significantly higher sensitivity than those of the 2018 KLCA-NCC (85.3% vs. 78.3%, P=0.002) with identical specificity (93.6%). On HBA-MRI, the sensitivity and specificity of "definite" or "probable" HCC categories of both 2018 and 2022 KLCA-NCC were not significantly different (83.3% vs. 83.6%, P>0.999 and 92.1% vs. 90.8%, P>0.999, respectively). In "definite" HCC category of both 2018 and 2022 KLCA-NCC, HBA-MRI provides better sensitivity than ECA-MRI without compromising specificity. On ECA-MRI, "definite" or "probable" HCC categories of the 2022 KLCA-NCC may improve sensitivity in the diagnosis of HCC compared with the 2018 KLCA-NCC.

VICT2 Trait: Prognostic Alternative to Peritumoral Hepatobiliary Phase Hypointensity in HCC.

Background Peritumoral hepatobiliary phase (HBP) hypointensity is an established prognostic imaging feature in hepatocellular carcinoma (HCC), often associated with microvascular invasion (MVI). Similar prognostic features are needed for non-HBP MRI. Purpose To propose a non-hepatobiliary-specific MRI tool with similar prognostic value to peritumoral HBP hypointensity. Materials and Methods From December 2011 to November 2021, consecutive patients with HCC who underwent preoperative contrast-enhanced MRI were retrospectively enrolled and followed up until recurrence. All MRI scans were reviewed by two blinded radiologists with 7 and 10 years of experiences with liver MRI. A scoring system based on non-hepatobiliary-specific features that highly correlated with peritumoral HBP hypointensity was identified in a stratified sampling-derived training set of the gadoxetate disodium (EOB) group by means of multivariable logistic regression, and its values to predict MVI and recurrence-free survival (RFS) were assessed. Results There were 660 patients (551 men; median age, 53 years; IQR, 45-61 years) enrolled. Peritumoral portal venous phase hypoenhancement (odds ratio [OR] = 8.8), incomplete "capsule" (OR = 3.3), corona enhancement (OR, 2.6), and peritumoral mild-moderate T2 hyperintensity (OR, 2.2) (all P < .001) were associated with peritumoral HBP hypointensity and constituted the "VICT2 trait" (test set area under the receiver operating characteristic curve = 0.84; 95% CI: 0.78, 0.90). For the EOB group, both peritumoral HBP hypointensity (OR for MVI = 2.5, P = .02; hazard ratio for RFS = 2.5, P < .001) and the VICT2 trait (OR for MVI = 5.1, P < .001; hazard ratio for RFS = 2.3, P < .001) were associated with MVI and RFS, despite a higher specificity of the VICT2 trait for MVI (89% vs 80%, P = .01). These values of the VICT2 trait were confirmed in the extracellular contrast agent group (OR for MVI = 4.0; hazard ratio for RFS = 1.7; both P < .001). Conclusion Based on four non-hepatobiliary-specific MRI features, the VICT2 trait was comparable to peritumoral hepatobiliary phase hypointensity in predicting microvascular invasion and postoperative recurrence of hepatocellular carcinoma. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Intraindividual Comparison of MRIs with Extracellular and Hepatobiliary Contrast Agents for the Noninvasive Diagnosis of Hepatocellular Carcinoma Using the Korean Liver Cancer Association-National Cancer Center 2022 Criteria.

The aim of the present study was to evaluate the per-lesion sensitivity and specificity of the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) 2022 criteria for the noninvasive diagnosis of hepatocellular carcinoma (HCC), with intraindividual comparison of the diagnostic performance of magnetic resonance imaging with extracellular agents (ECA-MRI) and hepatobiliary agents (HBA-MRI). Patients at high risk for HCC who were referred to a tertiary academic institution for hepatic lesions with size ≥ 10 mm between July 2019 and June 2022 were enrolled. A total of 91 patients (mean age, 58.1 years; 76 men and 15 women) with 118 lesions who underwent both ECA-MRI and HBA-MRI were eligible for final analysis. The per-lesion sensitivities and specificities of the KLCA-NCC 2022 criteria using ECA-MRI and HBA-MRI were compared using McNemar's test. The 118 lesions were 93 HCCs, 4 non-HCC malignancies, and 21 benign lesions. On HBA-MRI, the "definite" HCC category showed significantly higher sensitivity than ECA-MRI (78.5% vs. 58.1%, p < 0.001), with identical specificity (92.0% vs. 92.0%, p > 0.999). For "probable" or "definite" HCC categories, there were no differences in the sensitivity (84.9% vs. 84.9%, p > 0.999) and specificity (84.0% vs. 84.0%, p > 0.999) between ECA-MRI and HBA-MRI. The "definite" HCC category of the KLCA-NCC 2022 criteria showed higher sensitivity in diagnosing HCC on HBA-MRI compared with ECA-MRI, without compromising specificity. There were no significant differences in the sensitivity and specificity of "probable" or "definite" HCC categories according to ECA-MRI and HBA-MRI.

Percentages of Hepatocellular Carcinoma in LI-RADS Categories with CT and MRI: A Systematic Review and Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) CT and MRI algorithm applies equally to CT, MRI with extracellular contrast agents (ECA-MRI), and MRI with gadoxetate (Gx-MRI). Purpose To estimate pooled percentages of hepatocellular carcinoma (HCC) and overall malignancy for each LI-RADS category with CT and MRI. Materials and Methods MEDLINE and EMBASE databases were searched for research articles (January 2014-April 2021) reporting the percentages of observations in each LI-RADS category with use of versions 2014, 2017, or 2018. Study design, population characteristics, imaging modality, reference standard, and numbers of HCC and non-HCC malignancies in each category were recorded. A random-effects model evaluated the pooled percentage of HCC and overall malignancy for each category. Results There were 49 studies with 9620 patients and a total 11 562 observations, comprising 7921 HCCs, 1132 non-HCC malignancies, and 2509 benign entities. No HCC or non-HCC malignancies were reported with any modality in the LR-1 category. The pooled percentages of HCC for CT, ECA-MRI, and Gx-MRI, respectively, were 10%, 6%, and 1% for LR-2 (P = .16); 48%, 31%, and 38% for LR-3 (P = .42); 76%, 64%, and 77% for LR-4 (P = .62); 96%, 95%, and 96% for LR-5 (P = .76); 88%, 76%, and 78% for LR-5V or LR-TIV (tumor in vein) (P = .42); and 20%, 30%, and 35% for LR-M (P = .32). Most LR-M (93%-100%) and LR-5V or LR-TIV (99%-100%) observations were malignant, regardless of modality. Conclusion There was no difference in percentages of hepatocellular carcinoma and overall malignancy between CT, MRI with extracellular contrast agents, and MRI with gadoxetate for any Liver Imaging Reporting and Data System categories. © RSNA, 2023 Supplemental material is available for this article See also the editorial by Ronot in this issue.

MR imaging of hepatocellular carcinoma: prospective intraindividual head-to-head comparison of the contrast agents gadoxetic acid and gadoteric acid

The routine use of dynamic-contrast-enhanced MRI (DCE-MRI) of the liver using hepatocyte-specific contrast agent (HSCA) as the standard of care for the study of focal liver lesions is not widely accepted and opponents invoke the risk of a loss in near 100% specificity of extracellular contrast agents (ECA) and the need for prospective head-to-head comparative studies evaluating the diagnostic performance of both contrast agents. The Purpose of this prospective intraindividual study was to conduct a quantitative and qualitative head-to-head comparison of DCE-MRI using HSCA and ECA in patients with liver cirrhosis and HCC. Twenty-three patients with liver cirrhosis and proven HCC underwent two 3 T-MR examinations, one with ECA (gadoteric acid) and the other with HSCA (gadoxetic acid). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), wash-in, wash-out, image quality, artifacts, lesion conspicuity, and major imaging features of LI-RADS v2018 were evaluated. Wash-in and wash-out were significantly stronger with ECA compared to HSCA (P < 0.001 and 0.006, respectively). During the late arterial phase (LAP), CNR was significantly lower with ECA (P = 0.005), while SNR did not differ significantly (P = 0.39). In qualitative analysis, ECA produced a better overall image quality during the portal venous phase (PVP) and delayed phase (DP) compared to HSCA (P = 0.041 and 0.008), showed less artifacts in the LAP and PVP (P = 0.003 and 0.034) and a higher lesion conspicuity in the LAP and PVP (P = 0.004 and 0.037). There was no significant difference in overall image quality during the LAP (P = 1), in artifacts and lesion conspicuity during the DP (P = 0.078 and 0.073) or in the frequency of the three major LI-RADS v2018 imaging features. In conclusion, ECA provides superior contrast of HCC—especially hypervascular HCC lesions—in DCE-MR in terms of better perceptibility of early enhancement and a stronger washout.

An activatable Mn(II) MRI probe for detecting peroxidase activity in vitro and in vivo

Myeloperoxidase (MPO), a hallmark of the function and activation of innate immune cells, can act as a ‘double-edged sword’, contributing to clear infection as well as causing tissue oxidizing damage in various inflammatory diseases. In this study, an activatable Mn(II) chelate-based magnetic resonance imaging (MRI) contrast agent (CA), Mn-TyEDTA (TyEDTA = tyrosine derived ethylenediaminetetraacetic acid) structurally featuring a phenol group as the electron-donor, was developed to sense the activity of peroxidase in vitro and in vivo. Mn-TyEDTA demonstrated a peroxidase activity-dependent relaxivity in the presence of horseradish peroxidase (HRP)/H2O2 with more than a 2.6-fold increase in water proton relaxivity produced (HRP, 500 U; H2O2, 4.5 eq). A mechanism of peroxidase-mediated Mn(II) monomer radical polymerization was confirmed with those oligomers of Mn-TyEDTA such as dimer, trimer and tetramer were found in the LC-MS study. Dynamic MR imaging of normal mice revealed rapid blood clearance and mixed renal and hepatobiliary elimination of Mn-TyEDTA. Furthermore, compared to liver-specific and non-specific extracellular contrast agents (Mn-BnO-TyEDTA (BnO-TyEDTA = benzyl tyrosine-derived ethylenediaminetetraacetic acid) and Gd-DTPA (DTPA = diethylene triamine penta-acetic acid)), MRI on a monosodium urate (MSU) crystal-induced acute mice model of arthritis showed that inflamed tissues could be selectively enhanced by Mn-TyEDTA, suggesting that this peroxidase-activatable Mn(II) MRI probe could potentially be used for noninvasive detection of MPO activity in vivo.

Preclinical Profile of Gadoquatrane: A Novel Tetrameric, Macrocyclic High Relaxivity Gadolinium-Based Contrast Agent.

ObjectivesThe aim of this report was to characterize the key physicochemical, pharmacokinetic (PK), and magnetic resonance imaging (MRI) properties of gadoquatrane (BAY 1747846), a newly designed tetrameric, macrocyclic, extracellular gadolinium-based contrast agent (GBCA) with high relaxivity and stability.Materials and MethodsThe r1-relaxivities of the tetrameric gadoquatrane at 1.41 and 3.0 T were determined in human plasma and the nuclear magnetic relaxation dispersion profiles in water and plasma. The complex stability was analyzed in human serum over 21 days at pH 7.4 at 37°C and was compared with the linear GBCA gadodiamide and the macrocyclic GBCA (mGBCA) gadobutrol. In addition, zinc transmetallation assay was performed to investigate the kinetic inertness. Protein binding and the blood-to-plasma ratio were determined in vitro using rat and human plasma. The PK profile was evaluated in rats (up to 7 days postinjection). Magnetic resonance imaging properties were investigated using a glioblastoma (GS9L) rat model.ResultsThe new chemical entity gadoquatrane is a macrocyclic tetrameric Gd complex with one inner sphere water molecule per Gd (q = 1). Gadoquatrane showed high solubility in buffer (1.43 mol Gd/L, 10 mM Tris-HCl, pH 7.4), high hydrophilicity (logP −4.32 in 1-butanol/water), and negligible protein binding. The r1-relaxivity of gadoquatrane in human plasma per Gd of 11.8 mM−1·s−1 (corresponding to 47.2 mM−1·s−1 per molecule at 1.41 T at 37°C, pH 7.4) was more than 2-fold (8-fold per molecule) higher compared with established mGBCAs. Nuclear magnetic relaxation dispersion profiles confirmed the more than 2-fold higher r1-relaxivity in human plasma for the clinically relevant magnetic field strengths from 0.47 to 3.0 T. The complex stability of gadoquatrane at physiological conditions was very high. The observed Gd release after 21 days at 37°C in human serum was below the lower limit of quantification. Gadoquatrane showed no Gd3+ release in the presence of zinc in the transmetallation assay. The PK profile (plasma elimination, biodistribution, recovery) was comparable to that of gadobutrol. In MRI, the quantitative evaluation of the tumor-to-brain contrast in the rat glioblastoma model showed significantly improved contrast enhancement using gadoquatrane compared with gadobutrol at the same Gd dose administered (0.1 mmol Gd/kg body weight). In comparison to gadoterate meglumine, similar contrast enhancement was reached with gadoquatrane with 75% less Gd dose. In terms of the molecule dose, this was reduced by 90% when compared with gadoterate meglumine. Because of its tetrameric structure and hence lower number of molecules per volume, all prepared formulations of gadoquatrane were iso-osmolar to blood.ConclusionsThe tetrameric gadoquatrane is a novel, highly effective mGBCA for use in MRI. Gadoquatrane provides favorable physicochemical properties (high relaxivity and stability, negligible protein binding) while showing essentially the same PK profile (fast extracellular distribution, fast elimination via the kidneys in an unchanged form) to established mGBCAs on the market. Overall, gadoquatrane is an excellent candidate for further clinical development.

Reliability of extracellular contrast versus gadoxetic acid in assessing small liver lesions using liver imaging reporting and data system v.2018 and European association for the study of the liver criteria.

The diagnostic accuracy of Liver Imaging Reporting and Data System (LI-RADS) v.2018 and European Association for the Study of the Liver (EASL) criteria for the diagnosis of HCC have been widely evaluated, but their reliability should be investigated. We aimed to assess and compare the reliability of LI-RADS v.2018 and EASL criteria for the diagnosis of HCC using MRI with extracellular contrast agents (ECAs) and gadoxetic acid (GA) and determine the effect of ancillary features on LI-RADS reliability. Ten readers reviewed MRI studies of 92 focal liver lesions measuring <3 cm acquired with ECAs and GA <1 month apart from two prospective trials, assessing EASL criteria, LI-RADS major and ancillary features, and LI-RADS categorization with and without including ancillary features. Inter-reader agreement for definite HCC diagnosis was substantial and similar for the two contrasts for both EASL and LI-RADS criteria. For ECA-MRI and GA-MRI, respectively, inter-reader agreement was k = 0.72 (95% CI, 0.63-0.81) and k = 0.72 (95% CI, 0.63-0.80); for nonrim hyperenhancement, k = 0.63 (95% CI, 0.54-0.72) and k = 0.57 (95% CI, 0.48-0.66); and for nonperipheral washout, k = 0.49 (95% CI, 0.40-0.59) and k = 0.48 (95% CI, 0.37-0.58) for enhancing capsule. The inter-reader agreement for LI-RADS after applying ancillary features remained in the same range of agreement. Agreement for definite HCC was substantial and similar for both scoring systems and the two contrast agents in small focal liver lesions. Agreement for LI-RADS categorization was lower for both contrast agents, and including LI-RADS ancillary features did not improve agreement.

Albumin-templated manganese carbonate nanoparticles for precise magnetic resonance imaging of acute myocardial infarction.

Myocardial infarction (MI) is a major cause of death worldwide. Early and precise diagnosis of myocardial viability after MI is extremely important for effective treatment and prognosis evaluation. Herein, we developed the BSA-templated manganese carbonate (MnCO3@BSA) nanoparticles as an MR imaging contrast agent for accurate detection of the infarcted regions. The chemophysical features, targeting capability toward the infarct, and biocompatibility were evaluated. The nanoparticles showed superior chemical stability. In vitro study suggested that the MnCO3@BSA nanoparticles do not enter normal cardiomyocytes. MR imaging indicated that the MnCO3@BSA with a high longitudinal (r1) relaxivity of 5.84mM-1s-1 at physiological condition specifically accumulated into the infarcted regions of myocardial ischemia/reperfusion (I/R) mice. In addition, the MnCO3@BSA nanoparticles exhibited low cytotoxicity to cardiomyocytes, no damage to organs and good hemocompatibility. Thereby, the MnCO3@BSA nanoparticles manifested great potential as an extracellular contrast agent of MR imaging for sensitive and specific detection of the infarcted regions during acute myocardial I/R injury.

New Liver MR Imaging Hallmarks for Small Hepatocellular Carcinoma Screening and Diagnosing in High-Risk Patients.

ObjectiveEarly detection and diagnosis of hepatocellular carcinoma (HCC) is essential for prognosis; however, the imaging hallmarks for tumor detection and diagnosis has remained the same for years despite the use of many new immerging imaging methods. This study aimed to evaluate the detection performance of hepatic nodules in high risk patients using either hepatobiliary specific contrast (HBSC) agent or extracellular contrast agent (ECA), and further to compare the diagnostic performances for hepatocellular carcinoma (HCC) using different diagnostic criteria with the histopathological results as reference standard.MethodsThis prospective study included 247 nodules in 222 patients (mean age, 53.32 ± 10.84 years; range, 22–79 years). The detection performance and imaging features of each nodule were evaluated in all MR sequences by three experienced abdominal radiologists. The detection performance of each nodule on all MR sequences were compared and further the diagnostic performance of various diagnostic criteria were evaluated.ResultsFor those patients who underwent ECA-MRI, the conventional imaging hallmark of “AP + PVP and/or DP” was recommended, as 60.19% diagnostic sensitivity, 80.95% specificity and 100% lesion detection rate. Additionally, for those patients who underwent HBSC-MRI, the diagnostic criteria of “DWI + HBP” was recommended. This diagnostic criteria demonstrated, both in all tumor size and for nodules ≤2 cm, higher sensitivity (93.07 and 90.16%, all p <0.05, respectively) and slightly lower specificity (64.71 and 87.50%, all p >0.05, respectively) than that of the European Association for the Study of the Liver (EASL) criteria.ConclusionsDifferent abbreviated MR protocols were recommended for patients using either ECA or HBSC. These provided imaging settings demonstrated high lesion detection rate and diagnostic performance for HCC.

Histogram peritumoral enhanced features on MRI arterial phase with extracellular contrast agent can improve prediction of microvascular invasion of hepatocellular carcinoma.

Preoperative microvascular invasion (MVI) prediction plays an important role in therapeutic decision-making of hepatocellular carcinoma (HCC). This study aimed to investigate the value of histogram based on the arterial phase (AP) of magnetic resonance imaging (MRI) with extracellular contrast agent compared with radiological features for predicting MVI of solitary HCC. In total, 113 patients with pathologically proven solitary HCC were retrospectively enrolled who received surgical resection and underwent preoperative abdominal MRI. The patients were divided into the ≤3 cm [small HCC (sHCC)] cohort and the >3 cm cohort. Based on pathological analysis of surgical specimens, the patients were classified into MVI negative (MVI-) and MVI positive (MVI+) groups. Peritumoral and intratumoral histogram features [mean, median, standard deviation (Std), coefficient of variation (CV), skewness, kurtosis] were acquired on AP subtraction images and radiological features [size, capsule, corona enhancement, corona enhancement thickness (CET), CET group]. Receiver operating characteristic (ROC) curve was constructed to assess predictive capability. Subgroup analysis of patients with a visible corona enhancement based on the CET cut-off value was performed. None of the features extracted from the intratumor area were significantly different between the MVI+ and MVI- groups in both cohorts. Histogram defined peritumoral (peri-) mean, median, kurtosis, and radiological features including CET and CET group were associated with MVI in sHCCs. Peri-mean, median, Std and radiological features including incomplete capsule, CET, and CET group were associated with MVI in HCC >3 cm. In multivariate logistic regression analysis, the CET group and peri-mean were independent predictors for HCC >3 cm with an area under the curve (AUC) of 0.741. Peri-mean was an independent predictor for sHCC (AUC =0.798). Subgroup analysis of the corona enhancement using 8 mm as a cut-off value showed 100% sensitivity and negative predictive value (NPV). Peritumoral AP enhanced degree on MRI showed an encouraging predictive performance for preoperative prediction of MVI, especially in sHCCs. CET ≤8 mm could be used as a negative predictive marker for MVI.

Diagnosis of Hepatocellular Carcinoma Using Gd-EOB-DTPA MR Imaging.

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; Gadoxetic acid; Gadoxetate disodium) is a hepatocyte-specific MR contrast agent. It acts as an extracellular contrast agent in the early phase after intravenous injection, and then is taken up by hepatocytes later. Using this contrast agent, we can evaluate the hemodynamics of the liver and liver tumors, and can therefore improve the detection and characterization of hepatocellular carcinoma (HCC). Gd-EOB-DTPA helps in the more accurate detection of hypervascular HCC than by other agents. In addition, Gd-EOB-DTPA can detect hypovascular HCC, which is an early stage of the multi-stage carcinogenesis, with a low signal in the hepatobiliary phase. In addition to tumor detection and characterization, Gd-EOB-DTPA contrast-enhanced MR imaging can be applied for liver function evaluation and prognoses evaluation. Thus, Gd-EOB-DTPA plays an important role in the diagnosis of HCC. However, we have to employ optimal imaging techniques to improve the diagnostic ability. In this review, we aimed to discuss the characteristics of the contrast media, optimal imaging techniques, diagnosis, and applications.

A modified LI-RADS: targetoid tumors with enhancing capsule can be diagnosed as HCC instead of LR-M lesions.

To elucidate whether the presence of enhancing capsule can be applied to establish a modified Liver Imaging Reporting and Data System (LI-RADS) to differentiate hepatocellular carcinoma (HCC) from non-HCC malignancies in extracellular contrast agent (ECA)-enhanced and hepatobiliary agent (HBA)-enhanced MRI. We enrolled 198 participants (161 men; mean age, 56.3 years) with chronic liver disease who underwent ECA-MRI and HBA-MRI before surgery for de novo hepatic nodule(s). Two reviewers assigned LI-RADS categories (v2018). We defined a "modified LR-5 category, which emphasizes enhancing capsule (mLR-5C)" over targetoid features and classifies tumors with both targetoid appearance and enhancing capsule as HCC instead of LR-M. We compared the diagnostic performance of conventional LI-RADS and modified LI-RADS criteria for both MRIs. A total of 258 hepatic nodules (194 HCCs, 43 benign lesions, and 21 non-HCC malignancies; median size, 19 mm) were analyzed. By conventional LI-RADS, 47 (18.2%) nodules (31 HCCs and 16 non-HCC malignancies) were categorized as LR-M. The mLR-5C criterion showed superior sensitivity (ECA-MRI, 76.6% vs. 67.0%; HBA-MRI, 60.4% vs. 56.3%; both p < 0.05) while maintaining high specificity (ECA-MRI, 93.8% vs. 98.4%; HBA-MRI, 95.3% vs. 98.4%; both p > 0.05) compared with the LR-5 criterion. Using the mLR-5C criterion, ECA-MRI exhibited higher sensitivity than HBA-MRI (76.6% vs. 60.4%, p < 0.001) and similar specificity (93.8% vs. 95.3%, p > 0.99). Our modified LI-RADS achieved superior sensitivity for diagnosing HCC, without compromising specificity compared with LR-5. ECA-MRI showed higher sensitivity in diagnosing HCC than HBA-MRI by applying the mLR-5C for LR-M lesions. • By conventional LI-RADS, 31 (16.0%) of 194 HCCs were categorized as LR-M. • Among 31 HCCs categorized as LR-M, 19 HCCs or 8 HCCs were recategorized as HCC on ECA-MRI or HBA-MRI, respectively, after applying the modified LR-5 category, which allocates targetoid lesions with enhancing capsule as mLR-5C instead of LR-M. • The mLR-5C showed superior sensitivity compared with the LR-5 in both MRIs (ECA-MRI, 76.6% vs. 67.0%; HBA-MRI, 60.4% vs. 56.3%, both p < 0.05), while maintaining high specificity (ECA-MRI, 93.8% vs. 98.4%; HBA-MRI, 95.3% vs. 98.4%; both p > 0.05).

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

PurposeThe 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 methodsThis 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. ResultsThe 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). ConclusionCapsule 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.

Intraindividual Comparison of Compressed Sensing-Accelerated Cartesian and Radial Arterial Phase Imaging of the Liver in an Experimental Tumor Model.

The aim of this study was to intraindividually compare the performance of 2 compressed sensing (CS)-accelerated magnetic resonance imaging (MRI) sequences, 1 featuring Cartesian (compressed sensing volumetric interpolated breath-hold examination [CS-VIBE]) and the other radial (golden-angle radial sparse parallel [GRASP]) k-space sampling in continuous dynamic imaging during hepatic vascular phases, using extracellular and hepatocyte-specific contrast agents. Seven New Zealand white rabbits, with induced VX2 liver tumors (median number of lesions, 2 ± 0.83; range, 1-3), received 2 continuously acquired T1-weighted prototype CS-accelerated MRI sequences (CS-VIBE and GRASP) with high spatial (0.8 × 0.8 × 1.5 mm) and temporal resolution (3.5 seconds) in randomized order on 2 separate days using a 1.5-T scanner. In all animals, imaging was performed using first gadobutrol at a dose of 0.1 mmol/kg and, then 45 minutes later, gadoxetic acid at a dose of 0.025 mmol/kg.The following qualitative parameters were assessed using 3- and 5-point Likert scales (3 and 5 being the highest scores respectively): image quality (IQ), arterial and venous vessel delineation, tumor enhancement, motion artifacts, and sequence-specific artifacts. Furthermore, the following quantitative parameters were obtained: relative peak signal enhancement, time to peak, mean transit time, and plasma flow ratios. Paired sampled t tests and Wilcoxon signed rank tests were used for intraindividual comparison. Image analysis was performed by 2 radiologists. Six of 7 animals underwent the full imaging protocol and obtained data were analyzed statistically. Overall IQ was rated moderate to excellent, not differing significantly between the 2 sequences.Gadobutrol-enhanced CS-VIBE examinations revealed the highest mean Likert scale values in terms of vessel delineation and tumor enhancement (arterial 4.4 [4-5], venous 4.3 [3-5], and tumor 2.9 [2-3]). Significantly, more sequence-specific artifacts were seen in GRASP examinations (P = 0.008-0.031). However, these artifacts did not impair IQ. Excellent Likert scale ratings were found for motion artifacts in both sequences. In both sequences, a maximum of 4 hepatic arterial dominant phases were obtained. Regarding the relative peak signal enhancement, CS-VIBE and GRASP showed similar results. The relative peak signal enhancement values did not differ significantly between the 2 sequences in the aorta, the hepatic artery, or the inferior vena cava (P = 0.063-0.536). However, significantly higher values were noted for CS-VIBE in gadoxetic acid-enhanced examinations in the portal vein (P = 0.031) and regarding the tumor enhancement (P = 0.005). Time to peak and mean transit time or plasma flow ratios did not differ significantly between the sequences. Both CS-VIBE and GRASP provide excellent results in dynamic liver MRI using extracellular and hepatocyte-specific contrast agents, in terms of IQ, peak signal intensity, and presence of artifacts.

Clinical practice guidelines for hepatocellular carcinoma between Korea, Europe, and United States

Clinical practice guidelines for hepatocellular carcinoma between Korea, Europe, and United States

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 Criteria and LI-RADS for Hepatocellular Carcinoma.

Diagnostic Criteria and LI-RADS for Hepatocellular Carcinoma.

Contrast-enhanced body magnetic resonance angiography: how we do it.

This review introduces the basic principles of contrast-enhanced magnetic resonance (MR) angiography and details four contrast-enhanced MR angiography sequences for body imaging with extracellular gadolinium-based contrast agents in pediatric patients. Specifically, this review covers (1) respiratory-navigated, cardiac-gated MR angiography; (2) time-resolved MR angiography; (3) conventional MR angiography; and (4) modified spoiled gradient echo variants. We present and discuss indications, technical considerations, sequence optimization, advantages and disadvantages, along with practical tips and illustrative case examples for each sequence.

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 < 2cm. 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.