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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.

Microvascular invasion (MVI) is an important risk factor in hepatocellular carcinoma (HCC), but its diagnosis mandates postoperative histopathologic analysis. We aimed to develop and externally validate a predictive scoring system for MVI.From July 2015 to November 2020, consecutive patients underwent surgery for HCC with preoperative gadoxetate disodium (EOB)-enhanced MRI was retrospectively enrolled. All MR images were reviewed independently by two radiologists who were blinded to the outcomes. In the training centre, a radio-clinical MVI score was developed via logistic regression analysis against pathology. In the testing centre, areas under the receiver operating curve (AUCs) of the MVI score and other previous MVI schemes were compared. Overall survival (OS) and recurrence-free survival (RFS) were analysed by the Kaplan-Meier method with the log-rank test.A total of 417 patients were included, 195 (47%) with pathologically-confirmed MVI. The MVI score included: non-smooth tumour margin (odds ratio [OR] = 4.4), marked diffusion restriction (OR = 3.0), internal artery (OR = 3.0), hepatobiliary phase peritumoral hypointensity (OR = 2.5), tumour multifocality (OR = 1.6), and serum alpha-fetoprotein400 ng/mL (OR = 2.5). AUCs for the MVI score were 0.879 (training) and 0.800 (testing), significantly higher than those for other MVI schemes (testing AUCs: 0.648-0.684). Patients with model-predicted MVI had significantly shorter OS (median 61.0 months vs not reached, P .001) and RFS (median 13.0 months vs. 42.0 months, P .001) than those without.A preoperative MVI score integrating five EOB-MRI features and serum alpha-fetoprotein level could accurately predict MVI and postoperative survival in HCC. Therefore, this score may aid in individualized treatment decision making.

The definition of washout in gadoxetate disodium-enhanced MRI (Gd-EOB-MRI) is controversial. The current Liver Imaging Reporting and Data System (LI-RADS) defines washout only in the portal venous phase on Gd-EOB-MRI, leading to low diagnostic sensitivity for HCC. We performed a meta-analysis to compare the diagnostic performance of Gd-EOB-MRI using conventional (cWO) and modified (mWO) definitions of washout.The PubMed and EMBASE databases were searched to identify studies published between January 1, 2010, and August 1, 2021, that compared the diagnostic performance of cWO and mWO for HCC. The mWOs added transition phase (TP) hypointensity (mWO-1), hepatobiliary phase (HBP) hypointensity (mWO-2), or both (mWO-3). The pooled sensitivity and specificity were calculated using a bivariate random-effects model. Study heterogeneity was explored by subgroup analysis and meta-regression analysis.Ten comparative studies with 2391 patients were included. Compared to cWO, the overall mWO yielded significantly higher sensitivity (71% vs. 81%, p = 0.00) and lower specificity (97% vs. 93%, p = 0.01) for diagnosing HCC. The area under the curve (AUC) was 0.90 and 0.94 for the cWO and mWO, respectively. Regarding the three types of mWOs, mWO-2 showed the highest sensitivity (85%) and specificity (96%) for diagnosing HCC. mWO-2 achieved the highest AUC (0.97), followed by mWO-1 (0.90), and mWO-3 (0.89). Average reviewer experience and scanner field strength were significantly associated with study heterogeneity (p0.05).Inclusion of TP and HBP hypointensity in the definition of washout improved the sensitivity with slightly lower specificity for diagnosing HCC in LI-RADS.• Compared to the conventional definition of washout, studies using a modified definition had higher sensitivity (71% vs. 81%) but lower specificity (97% vs. 93%) in LI-RADS for the diagnosis of HCC. • Hepatobiliary phase hypointensity may be a preferred alternative washout for HCC diagnosis with the highest area under the curve. • Studies with experienced reviewer or 3.0T MRI showed higher sensitivity and lower specificity for diagnosing HCC when using modified washout (p0.05).

Gadolinium-ethoxybenzyl-diethylene triamine pentaacetic acid (Gd-EOB-DTPA) is a newer magnetic resonance contrast that has the combined effect of conventional and liver-specific contrast. The use of Gd-EOB-DTPA may aid in management of patients with hepatocellular carcinoma (HCC) undergoing living donor liver transplant (LDLT).We retrospectively reviewed all HCC patients who received LDLT with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) as part of a pretransplant evaluation between October 2012 and October 2016. The detection rate and impact on decision making were assessed between multidetector-row computed tomography (MDCT) and Gd-EOB-DTPA-enhanced MRI with pathology of the explanted liver being the reference standard.We analyzed 25 patients with 80 nodules. Gd-EOB-DTPA-enhanced MRI showed superior detection rate for HCCs than MDCT (76.1% vs 35.8%). Among the 25 patients, 16 had additional HCCs detected by Gd-EOB-DTPA-enhanced MRI, which led to changes in therapeutic decisions in 11 patients. The recurrence rate and mortality rate were 4% (1 of 25). In the same period in our institution, the mortality rate was 13.9% (25 of 180) for those who did not receive Gd-EOB-DTPA-enhanced MRI as part of the pretransplant evaluation.The use of Gd-EOB-DTPA-enhanced MRI can aid in characterization of indeterminate nodules and detect more HCCs and thus more adequate downstaging and pretransplant neoadjuvant treatment ensue, which may lower the recurrence rate after LDLT.

The multiple arterial-phase (AP) technique was introduced for liver MRI, but it is not really known if multiple AP MRI (MA-MRI) improves image quality and lesion detection rate on gadoxetate disodium-enhanced MRI in comparison with single AP MRI (SA-MRI). We aimed to determine the clinical usefulness of MA-MRI in comparison with SA-MRI.Original articles reporting the percentage of adequate AP imaging and the lesion detection rate on gadoxetate disodium-enhanced MA-MRI were identified in PubMed, EMBASE, and Cochrane Library databases. The pooled percentage of adequate AP imaging and lesion detection rate were calculated using random-effects meta-analysis of single proportions. Subgroup analysis was performed to explain causes of study heterogeneity, and publication bias was evaluated using Egger's test.Of 772 articles screened, 22 studies in 12 articles were included: 18 studies (ten MA-MRI and eight SA-MRI) suitably defined the percentage of adequate AP imaging and four (three MA-MRI and one SA-MRI) defined the lesion detection rate. MA-MRI had 16.1% higher pooled percentage of adequate AP imaging than SA-MRI (94.8% vs. 78.7%, p0.01). MA-MRI additionally detected 33.2% of lesions than SA-MRI (83.2% vs. 50.0%, p = 0.06). Substantial study heterogeneity was found in MA-MRI, and the definition of adequate AP imaging, lesion characteristics, and reference standards were significant factors affecting study heterogeneity (p ≤ 0.02). Significant publication bias was found in MA-MRI (p0.01) but not in SA-MRI studies (p = 0.87).Gadoxetate disodium-enhanced MA-MRI may be more clinically useful than SA-MRI, but further study is necessary to validate this finding because of study heterogeneity and publication bias.• Multiple arterial-phase MRI (MA-MRI) had a 16.1% higher pooled percentage of adequate AP imaging than single arterial-phase MRI (SA-MRI) (94.8% vs. 78.7%, p0.01). • MA-MRI additionally detected an extra 33.2% of lesions compared with SA-MRI (83.2% vs. 50.0%, p = 0.06). • Substantial study heterogeneity and significant publication bias were found across MA-MRI studies.

The association of repeated administration of gadolinium-based contrast agents (GBCAs) with the gadolinium (Gd) retention in the brains of mother and fetus remains unclear.To investigate the effects of pregnancy and repeated administration of GBCAs on Gd retention in the brains of mother and pup mice.Cross-sectional cohort toxicity study.From gestational days 16-19, pregnant (n = 48) BALB/c mice.A 9.4 T and fast spin echo sequence.Half of the mother mice (n = 24) were killed at postnatal day 1 (P1) for inductively coupled plasma mass spectrometry (ICP-MS) and transmission electron microscopy (TEM). Besides the ICP-MS and TEM, four pups were randomly selected from each mother and killed at P1 for ultraperformance liquid chromatography mass spectrometry (UPLC-MS) and Nissl staining.One-way analysis of variance and unpaired t-test.In the group of gadodiamide, retention of Gd in the brains of pregnant mice was significantly lower than that of nonpregnant mice in the area of the deep cerebellar nuclei (DCN) (10.35 ± 2.16 nmol/g vs. 18.74 ± 3.65 nmol/g). Retention of Gd in the DCN of pups whose mothers were administered gadoterate meglumine was significantly lower than that of pups whose mothers were administered gadodiamide (0.21 ± 0.09 nmol/g vs. 6.15 ± 3.21 nmol/g) at P1. In mice treated with gadodiamide, most of the retained Gd in the brain tissue was insoluble (19.5% ± 9.5% of the recovered amount corresponded to the intact complex in the DCN).In different brain areas of the mother and pup mice, the retention of Gd after gadoterate meglumine administration was lower than that of gadodiamide and gadopentetate dimeglumine administration, and almost all the detected Gd in pups' brains was intact soluble GBCAs.1 TECHNICAL EFFICACY: Stage 2.

MRI is increasingly utilized for the diagnosis of liver disease and focal liver lesions. Although liver-targeted gadolinium-based contrast agents (GBCAs) have high efficacy, there continue to be safety concerns regarding release of toxic Gd(III) ions. Herein, Mn(EOB-PC2A) is synthesized as a nongadolinium alternative for liver-specific MRI. Mn(EOB-PC2A) has an

To identify the imaging and clinical features of hepatic neuroendocrine tumors (NETs) associated with peritumoral hyperintensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging.Fifty-seven patients with hepatic NETs were enrolled. Based on the degree of peritumoral hyperintensity, patients were divided into three groups: group 0 (no peritumoral hyperintensity), group 1 (lower peritumoral hyperintensity), and group 2 (higher peritumoral hyperintensity). The imaging and clinical findings were compared among the three groups.Apparent diffusion coefficient (ADC) values of group 2 were significantly lower than those of group 0 and group 1. Atypical (cholangiocarcinoma-like) enhancement pattern in the arterial phase was significantly more frequently observed in group 2 as compared to that in group 0 and group 1. Group 2 patients showed significantly poorer progression-free survival than group 0 patients.Hepatic NETs with greater peritumoral hyperintensity exhibit greater malignant potential.

Several preclinical studies have reported the presence of gadolinium (Gd) in different chemical forms in the brain, depending on the class (macrocyclic versus linear) of Gd-based contrast agent (GBCA) administered. The aim of this study was to identify, with a special focus on insoluble species, the speciation of Gd retained in the deep cerebellar nuclei (DCN) of rats administered repeatedly with gadoterate or gadodiamide 4 months after the last injection.Three groups (N = 6/group) of healthy female Sprague-Dawley rats (SPF/OFA rats; Charles River, L'Arbresle, France) received a cumulated dose of 50 mmol/kg (4 daily intravenous administrations of 2.5 mmol/kg, for 5 weeks, corresponding to 80-fold the usual clinical dose if adjusted for man) of gadoterate meglumine (macrocyclic) or gadodiamide (linear) or isotonic saline for the control group (4 daily intravenous administrations of 5 mL/kg, for 5 weeks). The animals were sacrificed 4 months after the last injection. Deep cerebellar nuclei were dissected and stored at -80°C before sample preparation. To provide enough tissue for sample preparation and further analysis using multiple techniques, DCN from each group of 6 rats were pooled. Gadolinium species were extracted in 2 consecutive steps with water and urea solution. The total Gd concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Soluble Gd species were analyzed by size-exclusion chromatography coupled to ICP-MS. The insoluble Gd species were analyzed by single-particle (SP) ICP-MS, nanoscale secondary ion mass spectroscopy (NanoSIMS), and scanning transmission electron microscopy with energy-dispersive X-ray spectroscopy (STEM-EDX) for elemental detection.The Gd concentrations in pooled DCN from animals treated with gadoterate or gadodiamide were 0.25 and 24.3 nmol/g, respectively. For gadoterate, the highest amount of Gd was found in the water-soluble fractions. It was present exclusively as low-molecular-weight compounds, most likely as the intact GBCA form. In the case of gadodiamide, the water-soluble fraction of DCN was composed of high-molecular-weight Gd species of approximately 440 kDa and contained only a tiny amount (less than 1%) of intact gadodiamide. Furthermore, the column recovery calculated for this fraction was incomplete, which suggested presence of labile complexes of dissociated Gd3+ with endogenous molecules. The highest amount of Gd was detected in the insoluble residue, which was demonstrated, by SP-ICP-MS, to be a particulate form of Gd. Two imaging techniques (NanoSIMS and STEM-EDX) allowed further characterization of these insoluble Gd species. Amorphous, spheroid structures of approximately 100-200 nm of sea urchin-like shape were detected. Furthermore, Gd was consistently colocalized with calcium, oxygen, and phosphorous, strongly suggesting the presence of structures composed of mixed Gd/Ca phosphates. No or occasional colocalization with iron and sulfur was observed.A dedicated analytical workflow produced original data on the speciation of Gd in DCN of rats repeatedly injected with GBCAs. The addition, in comparison with previous studies of Gd speciation in brain, of SP element detection and imaging techniques allowed a comprehensive speciation analysis approach. Whereas for gadoterate the main fraction of retained Gd was present as intact GBCA form in the soluble fractions, for linear gadodiamide, less than 10% of Gd could be solubilized and characterized using size-exclusion chromatography coupled to ICP-MS. The main Gd species detected in the soluble fractions were macromolecules of 440 kDa. One of them was speculated to be a Gd complex with iron-binding protein (ferritin). However, the major fraction of residual Gd was present as insoluble particulate species, very likely composed of mixed Gd/Ca phosphates. This comprehensive Gd speciation study provided important evidence for the dechelation of linear GBCAs and offered a deeper insight into the mechanisms of Gd deposition in the brain.

This study aimed to establish a reliable diagnostic scoring model for the preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biochemical indicators.This retrospective study included 129 patients with HCC at our hospital from 2014 to 2020. Based on the intratumoral and peritumoral features on Gd-EOB-DTPA MRI and biochemical indicators, a scoring model was developed for preoperative prediction of MVI, and examined for diagnostic efficacy according to postoperative pathological results. The scoring model was further externally validated in an independent cohort of 63 HCC patients.Logistic regression analysis was performed to identify five parameters related to MVI, including maximum tumor diameter, peritumoral low intensity in the hepatobiliary phase, incomplete capsule, apparent diffusion coefficient (ADC), and [alkaline phosphatase (ALP) (U/L) + gamma-glutamyl transpeptidase (GGT) (U/L)] / lymphocyte count (× 10The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators provides a reliable tool for preoperative prediction of MVI in HCC patients.• The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators is practical for preoperative prediction of MVI in HCC patients. • AGLR is an independent risk factor for MVI. • The scoring model could help implement more appropriate interventions, potentially leading to precise and individualized treatments based on the biological characteristics of the tumor.

The Liver Imaging Reporting and Data System (LI-RADS) is widely used for diagnosing hepatocellular carcinoma (HCC), however, with unsatisfactory sensitivity, complex ancillary features, and inadequate integration with gadoxetate disodium (EOB)-enhanced MRI.To modify LI-RADS (mLI-RADS) on EOB-MRI.Secondary analysis of a prospective observational study.Between July 2015 and September 2018, 224 consecutive high-risk patients (median age, 51 years; range, 26-83; 180 men; training/testing sets: 169/55 patients) with 742 (median size, 13 mm; interquartile range, 7-27; 498 HCCs) LR-3/4/5 observations.3.0 T TThree radiologists (with 5, 5, and 10 years of experience in liver MR imaging, respectively) blinded to the reference standard (histopathology or imaging follow-up) reviewed all MR images independently. In the training set, the optimal LI-RADS version 2018 (v2018) features selected by Random Forest analysis were used to develop mLI-RADS via decision tree analysis.In an independent testing set, diagnostic performances of mLI-RADS, LI-RADS v2018, and the Korean Liver Cancer Association (KLCA) guidelines were computed using a generalized estimating equation model and compared with McNemar's test. A two-tailed P 0.05 was statistically significant.Five features (nonperipheral "washout," restricted diffusion, nonrim arterial phase hyperenhancement [APHE], mild-moderate T2 hyperintensity, and transitional phase hypointensity) constituted mLI-RADS, and mLR-5 was nonperipheral washout coupled with either nonrim APHE or restricted diffusion. In the testing set, mLI-RADS was significantly more sensitive (72%) and accurate (80%) than LI-RADS v2018 (sensitivity, 61%; accuracy 74%; both P 0.001) and the KLCA guidelines (sensitivity, 64%; accuracy 74%; both P 0.001), without sacrificing positive predictive value (mLI-RADS, 94%; LI-RADS v2018, 94%; KLCA guidelines, 92%).In high-risk patients, the EOB-MRI-based mLI-RADS was simpler and more sensitive for HCC than LI-RADS v2018 while maintaining high positive predictive value.2 TECHNICAL EFFICACY: Stage 2.

To determine the value of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) from the hepatobiliary phase for predicting poor outcome in acute-on-chronic liver failure (ACLF) patients.In this single-center retrospective study, 74 patients diagnosed as ACLF who underwent Gd-BOPTA-enhanced hepatobiliary magnetic resonance imaging were collected. The quantitative liver-spleen contrast ratio (Q-LSC) and the relative enhancement ratio of the biliary system (REB) at the hepatobiliary phase were measured. Cox proportional hazards regression models were used to evaluate prognostic factors. The capacity of the Q-LSC and REB to predict the 90-day outcome was evaluated via receiver operating characteristic (ROC) curve.During the follow-up period, twenty-eight of 74 ACLF patients (38%) had a poor outcome. The Q-LSC and REB were significant predictive factors (hazard ratio [HR] = 0.03 [0.002-0.54], p 0.05; HR = 0.07 [0.01-0.88], p 0.05) for prognosis in patients with ACLF. Moreover, the areas under the ROC curves of Q-LSC and REB for predicting poor outcome in patients with ACLF were 0.81 and 0.80, respectively. The most appropriate cutoff values for the Q-LSC and REB were 1.09 and 0.57, respectively. The ACLF patients with the Q-LSC ≤ 1.09 or REB ≤ 0.57 had a low cumulative survival.Gd-BOPTA-enhanced hepatobiliary phase MR imaging can predict poor outcome in patients with acute-on-chronic liver failure.• The quantitative liver-spleen contrast ratio at the hepatobiliary phase was a significant predictive prognostic factor in patients with acute-on-chronic liver failure. • The relative enhancement ratio of the biliary system at the hepatobiliary phase was a significant prognostic factor in patients with acute-on-chronic liver failure. • Gadobenate dimeglumine contrast-enhanced MR imaging from the hepatobiliary phase can predict poor outcome in patients with acute-on-chronic liver failure.

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.

Background Myocardial replacement fibrosis is one of the major histologic features of hypertrophic cardiomyopathy (HCM), but its characteristics have not been well delineated. Purpose To clarify the characteristics of replacement fibrosis in HCM and to evaluate the prognostic value of the regional extent of fibrosis. Materials and Methods This prospective study evaluated participants with HCM who underwent contrast-enhanced cardiac MRI from March 2011 to April 2019. For each participant, global and 16-segment extent of late gadolinium enhancement (LGE) in the left ventricle (LV) at cardiac MRI was analyzed. The primary end point was all-cause death. Results Among the 798 study participants enrolled (median age, 49 years [interquartile range {IQR}: 38-59 years]; 508 men), 588 (74%) underwent whole-exome sequencing. Thirty-five participants (4%) experienced death from any cause during a median follow-up of 2.9 years (IQR: 1.5-4.7 years). Spearman analysis showed weak correlations between the extent of LGE and wall thickness (LGE of global LV and maximal LV wall thickness

Background/Aim: Gadolinium has been reported to cause liver lobular necrosis and nephrogenic systemic fibrosis. However, its toxicity to the skin remains unknown. This study aimed to investigate the effect of a high dose of gadolinium-based contrast agent gadodiamide on the human keratinocyte HaCaT cell line. Materials and Methods: Cell viability was assessed using MTT assay, and autophagy was assessed using acridine orange and LysoTracker Red staining. Western blotting was performed to verify the changes in Bcl2 and Bax levels. Results: The viability of HaCaT cells was significantly suppressed after gadodiamide treatment. Interestingly, gadodiamide caused autophagic vacuoles, whereas the autophagy inhibitors 3-methyladenine and chloroquine significantly alleviated autophagic cell death. Simultaneously, gadodiamide induced apoptosis, which was reduced by caspase inhibitors. Gadodiamide also inhibited Bcl-2 expression and promoted Bax expression. Conclusion: Gadodiamide induced both autophagy and apoptosis in HaCaT cells. Physicians should carefully assess the gadodiamide dosage used clinically.

PURPOSE To evaluate the utility of T2-enhanced spin-echo imaging using the time-reversed gradient echo sequence (T2FFE imaging) in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI (Gd-EOB-MRI) for differentiating hemangiomas from metastatic tumors. METHODS A total of 61 patients with 133 liver lesions, including 37 hemangiomas and 96 metastatic tumors, were scanned by Gd-EOB-MRI. Four data sets were independently analyzed by two readers: (1) 3D fat-suppressed T2-weighted imaging (FS-T2WI) alone; (2) the combination of 3D FS-T2WI and T2FFE imaging in the HBP of Gd-EOB-MRI; (3) the combination of 3D FS-T2WI, diffusion-weighted imaging (DWI) with the b-value of 1000 s/mm2 and the apparent diffusion coefficient (ADC); and (4) a dynamic study of Gd-EOB-MRI. After classifying the lesion sizes as ≤ 10 mm or > 10 mm, we conducted a receiver-operating characteristic analysis to compare diagnostic accuracies among the four data sets for differentiating hemangiomas from metastatic tumors. RESULTS The areas under the curves (AUCs) of the four data sets of two readers were: (1) ≤ 10 mm (0.85 and 0.91) and > 10 mm (0.88 and 0.97), (2) ≤ 10 mm (0.94 and 0.94) and > 10 mm (0.96 and 0.95), (3) ≤ 10 mm (0.90 and 0.87) and > 10 mm (0.89 and 0.95), and (4) ≤ 10 mm (0.62 and 0.67) and > 10 mm (0.76 and 0.71), respectively. Data sets (2) and (3) showed no significant differences in AUCs, but both showed significantly higher AUCs compared to that of (4) regardless of the lesion size (P < 0.05). CONCLUSION The combination of 3D FS-T2WI and T2FFE imaging in the HBP of Gd-EOB-MRI achieved an accuracy equivalent to that of the combination of 3D FS-T2WI, DWI, and ADC and might be helpful in differentiating hemangiomas from metastatic tumors.

To evaluate the predictive value of gadoxetic acid-enhanced MRI features (focused on Liver Imaging Reporting and Data System (LI-RADS) v2018 features and non-LI-RADS imaging features) for microvascular invasion (MVI) of hepatocellular carcinoma (HCC).From October 2018 to December 2020, 134 patients who underwent gadoxetic acid-enhanced MRI with a pathological diagnosis of HCC after hepatectomy were enrolled in this retrospective study. Two radiologists assessed the pre-hepatectomy LI-RADS v2018 imaging features and non-LI-RADS features to identify independent predictors of MVI of HCC with a logistic regression model.Four MRI features were found to be independent predictors of MVI: corona enhancement [odds ratio (OR) 5.787; 95% confidence interval (CI) 1.180, 28.369; p = 0.030], mosaic architecture (OR 7.097; 95% CI 1.299, 38.783; p = 0.024), nonsmooth tumor margin (OR 13.131; 95% CI 3.950, 43.649; p 0.001), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR 33.123; 95% CI 2.897, 378.688; p = 0.005). When one of four imaging features was present, the sensitivity was 93.2% (41/44), and the specificity was 71.1% (64/90).The four imaging features including corona enhancement, mosaic architecture, nonsmooth tumor margin, and peritumoral hypointensity on HBP can be used as preoperative imaging biomarkers for predicting MVI in patients at high risk for HCC. When one of the four imaging features is present, MVI can be predicted with a sensitivity 90%.

The aim of this study was to report early clinical experience with various forms of immune dampening to mitigate the expected flare reaction in patients suffering from gadolinium deposition disease (GDD) receiving DTPA chelation.All patients were clinical subjects, and no prospective research was performed on them. The study included 31 consecutive patients (21 women; age, 46.2 ± 12.5 years). The diagnosis of GDD was clinically made. The severity of the flare over the week after each chelation session was rated on a scale from 1 to 10 (where 1 is negligible, 10 is intolerably severe). Patients were followed for up to 5 chelation sessions. Four immune dampening strategies were used: (1) no concurrent treatment; (2) antihistamine plus montelukast (AH); (3) steroid/antihistamine taper postchelation (SAHT); and (4) steroid/antihistamine extending from prechelation to 5 days postchelation (extended hypersensitivity medication regimen; EHMR). The data were analyzed with generalized linear mixed models and with linear regression.A total of 102 flare scores were obtained at different time points. Ten patients underwent 5 chelations. The severity of the flare after the first chelation was significantly higher in cases of no concurrent therapy (8.4 ± 2.6) and AH (7 ± 1.4) compared with SAHT (6 ± 1.3) and EHMR (5 ± 1.1). Patients who underwent SAHT and EHMR experienced less severity of flare after the first chelation (P = 0.0049 and P = 0.0005, respectively). Considering all time points, the results were also significantly better with SAHT and EHMR.Based on early clinical experience, EHMR seems to manage flare reactions in DTPA chelation well. This strategy may represent the first standard therapy in patients with GDD.

To compare contrast-enhanced transabdominal ultrasonography (CE-US) following contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with enhanced magnetic resonance imaging using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB-MRI) in the diagnosis of liver metastases in patients with pancreatic cancer.Patients who underwent contrast-enhanced computed tomography for possible pancreatic cancer and required further evaluation with CH-EUS were enrolled in this study, and the diagnostic performance of CE-US following CH-EUS for liver metastasis was compared with that of EOB-MRI.A total of 228 patients were included in the final analysis. Two hundred thirty-four hepatic lesions were found in 81 patients, and 178 lesions were finally diagnosed as metastases. EOB-MRI had a higher sensitivity (0.837 vs 0.949), while CE-US had a higher specificity and positive predictive value (PPV) (0.982 and 0.993 vs 0.911 and 0.971, respectively) in the diagnosis of liver metastasis. CE-US with defect reperfusion imaging had a higher diagnostic performance than EOB-MRI (0.866 vs 0.667) in the differentiation between liver metastasis and abscess.EOB-MRI had a higher sensitivity than CE-US for diagnosing liver metastasis in patients with pancreatic cancer, but CE-US following CH-EUS demonstrated a higher specificity and PPV than EOB-MRI and was especially useful in the differentiation between liver metastasis and abscess.

3D-fluid attenuation inversion recovery (FLAIR) collected 4 h after intravenous gadolinium injection can delineate the perilymphatic space (PLS) from the endolymphatic space (ELS) to capture endolymphatic hydrops, the pathological counterpart of Ménière's disease. We aimed to optimize visualization of such inner ear internal anatomy using 3D-FLAIR without injection.3D-FLAIR signal from different fluid compartments such as PLS and ELS was first simulated. Then, twenty-two healthy subjects were scanned at 3.0-T MRI with non-injected 3D-FLAIR using variable T2 preparations (T2Preps) (OFF, 200, 400, and 600 ms) and variable inversion times (TIs) (from 224 to 5000 ms) and different resolutions (1.0 × 1.0 × 1.5, 0.6 × 0.6 × 0.8, and 0.6 × 0.6 × 0.6 mmThe PLS and ELS were differentiated when T2Prep was used but not without. The relative contrast was larger with T2Prep at 400 ms than at 200 or 600 ms (0.72 ± 0.22 vs. 0.44 ± 0.11, p = 0.019; and 0.72 ± 0.22 vs. 0.46 ± 0.28, p = 0.034, respectively). The saccule and utricle were best delineated in 87. % cases with T2Prep = 400 and TI = 2100 ms at the highest resolution. Visualization of the saccule and utricle in the optimized non-injected 3D-FLAIR was similar to conventional injected 3D-FLAIR in a patient.Combining a specific T2Prep and TI in non-injected 3D-FLAIR could separate PLS and ELS and even the saccule and utricle, paving the way toward future application to diagnose Ménière's disease.• MRI can capture the internal anatomy of inner ear without injection of contrast media. • Specific parameters consisting of a T2 preparation of 400 ms and an inversion time of 2100 ms must be used to visualize the saccule and utricle on non-injected 3D-FLAIR.

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. (c) 2021 Societe francaise de radiologie. Published by Elsevier Masson SAS. All rights reserved.

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.

Background There is considerable overlap in radiologic features of tubercular and malignant spinal lesions on conventional magnetic resonance imaging (MRI). Purpose To evaluate the role of dynamic contrast-enhanced (DCE) MRI perfusion parameters in differentiating vertebral malignancy from spinal tuberculosis. Material and Methods This was a prospective study and we enrolled consecutive patients presenting with a clinical/radiologic evidence of vertebral lesions. DCE-MRI of the spine was performed using 3D volume interpolated breath-hold examination (VIBE) sequence after intravenously injecting 0.1 mmol/kg body weight of gadopentetate dimeglumine. We used Tofts model to calculate DCE parameters that included Ktrans (transfer constant), kep (rate constant), ve (fractional volume of extracellular extravascular space), and iAUC (initial area under the curve). We compared the mean value of each perfusion parameter by type of lesion (tubercular/malignant) at 0.05 significance level and performed receiver operating characteristic curve analysis. Results We could confirm histologic/cytologic diagnosis in 35 of the 45 patients recruited. Of these, 19 were tubercular and 16 were malignant lesions. The mean (± standard deviation) of kep (min−1) was significantly higher (2.89 ± 3.3) in malignant compared to tubercular lesions (0.81 ± 0.19), whereas ve was significantly lower in malignant (0.27 ± 0.13 mL/g) compared to benign lesions (0.47 ± 0.12 mL/g) at 0.05 significance level. kep cutoff of ≥1.17 min−1 had a sensitivity of 93.8% and specificity of 100% with a diagnostic accuracy of 94.4% in detecting malignant disease. Conclusion High kep is the single best predictor of malignant vertebral lesions. We recommend kep cutoff value of ≥1.17 min−1 that has high diagnostic accuracy in identifying malignant lesions.

The RAF1 expression affects prognosis in patients with hepatocellular carcinoma (HCC) treated with sorafenib. We examined the expression of sorafenib-targeted gene RAF1 to ascertain its relationship with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (MRI) characteristics. We also explored the predictive potential of RAF1 expression markers in the treatment of HCC. Sixty-five patients with HCC who underwent preoperative enhanced MRI scanning were included in this study. We analyzed the qualitative and quantitative characteristics of enhanced MRI findings in patients with HCC. Immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) analyses were used to detect the protein and mRNA expression levels of RAF1 in HCC. Correlation and logistic regression analyses were used to evaluate the relationship between these image features and the RAF1 gene expression levels in HCC. The IHC analysis indicated a significant difference in tumor thrombus group (P = 0.037), RT-PCR results revealed a significant between-group difference for both tumor margins (P = 0.033) and capsule (P = 0.04). Binary logistic regression analysis results suggest that independent MRI predictors were regular tumor margins [P = 0.035, odds ratio (OR) = 3.145, 95% confidence interval (CI) 1.087–9.103] and thrombus (P = 0.046, OR = 4.421, 95% CI 1.024–19.08) with high RAF1expression; the tumor capsule was not an independent predictor. We found a correlation between MRI features and the RAF1 gene expression, Regular tumor margin and the presence of tumor thrombus are indicators of high RAF1 expression in HCC. Enhanced MRI may be useful for identifying patients with HCC eligible for targeted treatment.

Gadolinium-based contrast agents (GBCAs) have been used in clinical Magnetic Resonance Imaging (MRI) for more than 30 years. However, there is increasing evidence that their dissociation in vivo leads to long-term depositions of gadolinium ions in the human body. In vitro experiments provide critical insights into kinetics and thermodynamic equilibria of underlying processes, which give hints towards the in vivo situation. We developed a time-resolved MRI relaxometry-based approach that exploits distinct relaxivities of Gd3+ in different molecular environments. Its applicability to quantify the transmetallation of GBCAs, the binding of Gd3+ to competing chelators, and the combined transchelation process is demonstrated. Exemplarily, the approach is applied to investigate two representative GBCAs in the presence of Zn2+ and heparin, which is used as a model for a macromolecular and physiologically occurring chelator. Opposing indirect impacts of heparin on increasing the kinetic stability but reducing the thermodynamic stability of GBCAs are observed. The relaxivity of resulting Gd-heparin complexes is shown to be essentially increased compared to that of the parent GBCAs so that they might be one explanation for observed long-term MRI signal enhancement in vivo. In forthcoming studies, the presented method could help to identify the most potent Gd-complexing macromolecular species.

Background: Post-operative pancreatic fistula (POPF) can be life-threatening, and gadoxetic acid-enhanced MRI is routinely performed in patients undergoing pancreatic surgery. However, previous reports have not investigated if gadoxetic acid-enhanced MRI can be used to predict POPF risk. Objective: This study aims to explore if gadoxetic acid-enhanced MRI can predict pancreatic fibrosis and the need for POPF treatment before surgery. Methods: We retrospectively analyzed gadoxetic acid-enhanced MR images from 142 patients who underwent pancreatic surgery between January 1, 2011, and April 30, 2018. Pre-dynamic signal intensity (SI) and values for the portal, transitional, and hepatobiliary phase standardized based on pre-dynamic study values were analyzed. The diameter of the main pancreatic duct (DMPD) was measured, and the degree of pancreatic fibrosis was classified as F0 – F3. We defined POPF higher than grade B as significant. Results: Odds ratios for combinations that led to any degree of fibrosis higher than grade B were defined as significant risk factors. The highest odds ratio was obtained for F0 vs. F1 – F3 (p = 0.038). DMPD (p < 0.001), pre-SI (p = 0.008), portal-SI/pre-SI (p < 0.001), transitional-SI/pre-SI (p < 0.001), and hepatobiliary-SI/pre-SI (p = 0.012) were significantly correlated with the presence of fibrosis. Moreover, the presence of fibrosis was best detected by DMPD (AUC = 0.777). Individual specificity values of transitional-SI/pre-SI and DMPD were 95.5% and 86.6%, respectively, and their combined specificity was 97.7%. Conclusion: The absence of pancreatic fibrosis is a risk factor for developing POPF higher than grade B. DMPD was the most useful diagnostic indicator for the presence of fibrosis among our analysis, and its specificity increased when combined with transitional-SI/pre-SI.

To visualize whole cancerous region including hypoxic cancer without radiation exposure, we developed meglumine-gadopentetate-glucose solution for 7.0-T magnetic resonance imaging. The infusion solution consists of meglumine-gadopentetate and glucose solutions, and these solutions are mixed before the vein drip infusion. We used readily available solutions, and the concentrations of the meglumine-gadopentetate and glucose solutions were 37.14 and 5.0%, respectively. In the first and second experiments, vein infusions were conducted from a rabbit ear using meglumine-gadopentetate-saline and meglumine-gadopentetate-glucose solutions, and T1 weighted imaging was performed to visualize cancerous region. Using the meglumine-gadopentetate saline, it was not difficult to image cancer-growth regions with new blood vessels. Using the meglumine-gadopentetate-glucose solution, the signal intensity of whole cancerous region including hypoxic cancer substantially increased. The visualizing duration for the meglumine gadopentetate glucose was beyond 90 min, and the rabbit survived after the infusion. The signal intensity in the hypoxic cancer was increasing until 90 min using the meglumine-gadopentetate-glucose solution, since the meglumine-gadopentetate molecules were absorbed into almost the whole cancerous region along with glucose-molecule flows.

BACKGROUND/AIM Detection of hepatocellular carcinoma using intraoperative ultrasonography (IOUS) is indispensable for successful laparoscopic hepatectomy (LH). This study was performed to evaluate patients with intraoperatively unidentified tumours undergoing LH. PATIENTS AND METHODS Seven patients who underwent LH for hepatocellular carcinoma and whose tumours were not detected using IOUS were included in this study. Clinical features, preoperative imaging, intraoperative imaging, surgical procedures, and pathological findings were evaluated. RESULTS Using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, all the tumours were enhanced in the arterial phase and rapidly washed out, becoming hypointense to the remainder of the liver. All tumours except one were

Background Sinusoidal obstruction syndrome (SOS) due to chemotherapy can cause severe hepatotoxicity, leading to impaired outcome in patients with colorectal cancer. A previous study introduced gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to diagnose SOS. Purpose To assess the reproducibility of Gd-EOB-MRI-based SOS diagnosis and its relationship with response to chemotherapy and long-term outcome. Material and Methods Twenty-six Gd-EOB-MRI scans of patients undergoing chemotherapy for colorectal liver metastases (CRLM) were retrospectively analyzed. Three radiologists, blinded to clinical data, independently scored presence and severity of SOS on a 5-point scale (0, definitely not present to 4, definitely present). Patients with a score ≥3 were considered SOS+. Inter-observer agreement between readers was assessed with kappa statistics. Response (RECIST 1.1.), occurrence of new CRLM during follow-up (hepatic progression) and overall survival (OS) were compared between patients with and without SOS. Results The inter-observer agreement of SOS scores was poor, with quadratic kappas of 0.17–0.40. For the binary outcome of SOS+ (confidence level [CL] 3–4) vs. SOS– (CL 0–2) agreement was poor, with kappas of 0.03–0.37. Median follow-up was 24 months (range 4–44 months). Response and OS between patients with and without SOS did not differ significantly for any of the readers. Conclusion Inter-observer agreement for the diagnosis of SOS on Gd-EOB-MRI is poor. No significant correlation with relevant outcomes was found for any of the readers. Therefore, MRI for SOS diagnosis might be less useful than previously reported. Other techniques should be explored to accurately diagnose SOS in absence of histological confirmation.

Background Hepatocellular carcinomas (HCCs) are heterogeneous neoplasms, and the prognosis varies based on the subtype. Two broad molecular classes of HCC have been proposed: a proliferative and a nonproliferative class. Purpose To evaluate the gadoxetate-enhanced MRI findings of the proliferative class HCC and its prognostic significance after surgery. Materials and Methods This retrospective cohort study evaluated patients with surgically resected treatment-naive single HCC (≤5 cm) who underwent hepatic resection from January 2010 through February 2013 and preoperative gadoxetate-enhanced MRI. A Cox proportional hazards model was used to determine the predictive factors for overall survival (OS), intrahepatic distant recurrence, and extrahepatic metastasis (EM). The mean follow-up period was 75.5 months ± 30.2 (standard deviation). Multivariable logistic regression was performed to determine factors associated with proliferative class HCC. Results A total of 158 patients (mean age, 57 years ± 11; 128 men and 30 women) were evaluated. Forty-two of the 158 HCCs (26.6%) were proliferative class HCCs (17 macrotrabecular-massive HCCs, 14 keratin 19-positive HCCs, 10 scirrhous HCCs, and one sarcomatoid HCC). The proliferative class was associated with worse OS (hazard ratio [HR], 3.1; 95% CI: 1.5, 6.0; P = .01) and higher rates of intrahepatic distant recurrence (HR, 1.83; 95% CI: 1.1, 2.9; P = .01) and EM (HR, 9.97; 95% CI: 3.2, 31.4; P 100 ng/mL) (OR, 4.18; 95% CI: 1.64, 10.7; P = .01) were independent predictors for proliferative HCC. The presence of rim APHE was associated with poor OS (HR, 2.4; 95% CI: 1.2, 4.9; P = .02) and higher rates of EM (HR, 7.4; 95% CI: 2.5, 21.7; P < .01). Conclusion The proliferative class of hepatocellular carcinoma (HCC) is an independent factor for poor overall survival with increased rates of intrahepatic and extrahepatic metastasis. Rim arterial phase hyperenhancement at gadoxetate-enhanced MRI may help to identify proliferative class HCC and predict poor overall survival and an increased incidence of extrahepatic metastasis. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Krinsky and Shanbhogue in this issue.