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Magnetic resonance angiography (MRA) contrast agents are extensively utilized in clinical practice due to their capability of improving the image resolution and sensitivity. However, the clinically approved MRA contrast agents have the disadvantages of a limited acquisition time window and high dose administration for effective imaging. Herein, albumin-coated gadolinium-based nanoparticles (BSA-Gd) were meticulously developed for in vivo ultrahigh-resolution MRA. Compared to Gd-DTPA, BSA-Gd exhibits a significantly higher longitudinal relaxivity ( r 1 = 76.7 mM -1 s -1 ), nearly 16-fold greater than that of Gd-DTPA, and an extended blood circulation time ( t 1/2 = 40 min), enabling a dramatically enhanced high-resolution imaging of microvessels (sub-200 μm) and low dose imaging (about 1/16 that of Gd-DTPA). Furthermore, the clinically significant fine vessels were successfully mapped in large mammals, including a circle of Willis, kidney and liver vascular branches, tumor vessels, and differentiated arteries from veins using dynamic contrast-enhanced MRA BSA-Gd, and have superior imaging capability and biocompatibility, and their clinical applications hold substantial promise.

Gadolinium (Gd) is one of the rare earth elements (REY) and is widely used in magnetic resonance imaging (MRI) contrast agents. Anthropogenic Gd enrichment has frequently been found in wastewater treatment plant effluents in industrialised countries, rising concerns regarding effects on aquatic biota. This study investigates the acute toxicity and sublethal effects of Gd in two forms, as inorganic salt (GdCl 3 ) and as Gd-based contrast agent (GBCA), on early life stages of zebrafish (Danio rerio). Nominal exposure concentrations ranged from 3 to 3000 μg L -1 , with an exposure duration of 96 h. None of the two tested compounds were acutely toxic to embryos and larvae. Similarly, we did not observe any effects on larval development and locomotive behaviour. However, we found significant changes in the brain activity of larvae exposed to the highest concentrations of GdCl 3 and the GBCA. Our findings show that Gd can have sublethal effects on developing fish at lower concentrations than reported previously, highlighting the necessity of investigating the long-term fate and effects of GBCAs released into the aquatic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The study aims at assessing the quantitative features which distinguish focal liver lesions (FLLs) in gadoxetic acid (GA) enhanced liver MRI and at determining whether these features can accurately differentiate benign from malignant lesions., Material and Methods: 107 patients with 180 unequivocal FLLs in previous examinations were included in a single-center retrospective study. All patients underwent a MRI test of the liver with GA. 99 benign and 74 malignant lesions were included. The group of benign lesions consisted of 60 focal nodular hyperplasias (FNH), 22 hemangiomas (HMG), 6 hepatic adenomas (HA), and 11 other benign lesions (1 angiomyolipioma, 6 lesions histopathology diagnoses as benign without further specification, or ones lacking features of malignancy, and 4 lesions radiologically diagnosed as benign which remained stable in the follow-up studies). The group of malignant lesions consisted of primary 51 hepatocellular carcinomas, 12 metastases, and 11 metastases from melanoma malignum (MM meta). 7 FLLs were excluded (4 cases of uncertain histopathological diagnosis, 2 cholangiocarcinomas, and 1 regenerative nodule). For the included lesions ROI (region of interest) measurements were taken by two observers in the T2-w, ADC (apparent diffusion coefficient) and in the T1-w sequence in the hepatobiliary phase (HBP). The interobserver agreement was evaluated with the Wilcoxon test. The Kruskal - Wallis, Mann - Whitney U and post hoc Dunn's tests were applied to assess if there were any significant differences in the ROI values between individual lesions. The variables with the p values of < 0.05 were considered statistically significant., Results: We found significant differences in the ROI values between lesions with p < 0.0001. Strikingly high ROI values in the T2-w sequence were found for HMG. The lowest ADC values were encountered for metastases and MM metastases. The highest ROI values in the HBP were found for FNH, and the lowest for metastases. We also found statistically significant differences in the ROI values between benign and malignant lesions with benign lesions presenting statistically higher ROI values compared to malignant lesions., Conclusions: There were significant differences in the ROI values among different types of FLLs. The predominant quantitative feature in the T2-w sequence was a strikingly high ROI value for HMG. Benign lesions presented statistically higher ROI values in the T2-w, ADC, and HBP sequences compared to malignant lesions. This was true for all lesions except for HA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Abstract: Next-generation gadolinium-based contrast agents (GBCAs), including both high relaxivity agents and targeted agents, and manganese-based agents with a high probably of commercial success are discussed in some depth. It is highly likely that gadopiclenol and gadoquatrane, both next-generation high relaxivity gadolinium-based compounds, will come in time to replace the current macrocyclic gadolinium chelates, despite the wide acceptance, very high safety profile, and high stability of the latter group. Current research has also made possible the development of 2 new targeted gadolinium chelates, which look very promising, with the potential to improve cancer detection (for both MT218 and ProCA32.collagen) as well as diseases of collagen (for the latter agent). Further work with manganese-based compounds, a topic left fallow for more than 20 years, has also now produced 2 agents with high potential for clinical use, one (manganese chloride tetrahydrate, administered orally) developed primarily for imaging of the liver and the other (Mn-PyC3A, administered intravenously) as a gadolinium-free replacement for the GBCAs. New detail has recently emerged regarding specific circumscribed subregions of the brain with specialized cytoarchitecture and functions in which high gadolinium concentrations are seen following injection of the linear agent gadodiamide. These findings pave the way for tailored functional neurological testing, specifically in patients at potential risk due to the continued wide use in many countries across the world of the linear GBCAs. The impact of artificial intelligence is also critically discussed, with its most likely applications being dose reduction and new clinical indications., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Study Aims: The sensitivity of the Liver Imaging Reporting and Data System (LI-RADS) in the diagnosis of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) was suboptimal. This study evaluated the LI-RADS diagnostic performance in HCC when modifying the definition of washout using the transition phase (TP) or hepatobiliary phase (HBP) hypointensity on EOB-MRI., Patients and Methods: This retrospective study included patients at high risk of HCC who underwent EOB-MRI from June 2016 to June 2021. Three modified LI-RADS (mLI-RADS) algorithms were formulated according to different definitions of washout as follows: (a) portal venous phase (PVP) or TP hypointensity, (b) PVP or HBP hypointensity, and (c) PVP or TP or HBP hypointensity. Diagnostic performance, including sensitivity, specificity, and accuracy, was compared between mLI-RADS and LI-RADS v2018 using McNemar's test., Results: A total of 379 patients with 426 pathologically confirmed hepatic observations (250 HCCs, 88 nonHCC malignancies, and 88 benign lesions) were included in our study. The sensitivity rates of mLI-RADS a-c (80.0 %, 80.8 %, and 80.8 %) were all higher than that of LI-RADS v2018 (74.4 %) (all p < 0.05). The specificity rates of mLI-RADS a-c (86.9 %, 85.8 %, and 85.8 %) were all slightly lower than that of LI-RADS v2018 (88.6 %), although no statistically significant difference was noted (all p > 0.05). The accuracies of the three mLI-RADS algorithms were the same and were all higher than that of LI-RADS v2018 (82.9 % vs. 80.3 %, all p < 0.05)., Conclusion: When the definition of washout appearance was extended to TP or HBP hypointensity on EOB-MRI, the diagnostic sensitivity of LI-RADS for HCC improved without decreasing specificity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding This study was funded by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-074C)., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to evaluate the capacity of gadopiclenol, a high-relaxivity gadolinium-based contrast agent to detect brain metastases in mice as a function of dose (0.08 mmol/kg or 0.1 mmol/kg) compared with gadobenate at 0.1 mmol/kg., Materials and Methods: Brain metastases were induced by ultrasound-guided intracardiac implantation of 1.10 5 MDA-MB-231Br cells in the left ventricle of 18 anesthetized Balb/c Nude nu/nu female mice. At day 28 ± 3 after cell injection, each mouse received 2 crossover intravenous injections at 24-hour intervals, randomly selected from 2 doses of gadopiclenol (0.08 mmol/kg or 0.1 mmol/kg) and gadobenate (0.1 mmol/kg) with n = 6 mice/group (3 groups). Brain magnetic resonance imaging sessions were performed at 4 weeks on a 2.35 T magnet with a 3-dimensional T1-weighted high-resolution gradient echo sequence, before and after each injection. Images were blindly and randomly analyzed to detect enhancing lesions. Contrast-to-noise ratio between the metastases and the surrounding healthy parenchyma was calculated, based on region-of-interest signal measurements. In 2 animals per group, an early time point was added to the protocol (day 22 ± 3) to evaluate the sensitivity of detection as a function of time. After the last imaging session, the presence and location of whole-brain metastases were confirmed by histology in 4 mice., Results: After gadopiclenol, approximately twice as many metastases were detected compared with gadobenate, regardless of the dose. Contrast-to-noise ratios of the detected metastases were 2.3 and 3.3 times higher with gadopiclenol at 0.08 mmol/kg and 0.1 mmol/kg, respectively, compared with gadobenate at 0.1 mmol/kg ( P < 0.0001). Gadopiclenol at the dose of 0.1 mmol/kg resulted in a 1.4-fold higher contrast compared with gadopiclenol at 0.08 mmol/kg ( P < 0.02). In a subset of mice that were imaged 1 week earlier, 2 metastases were detected with gadopiclenol and not with gadobenate., Conclusions: The high-relaxivity macrocyclic gadolinium-based contrast agent gadopiclenol allowed higher diagnostic performance for detecting brain enhancing metastases in terms of contrast-to-noise ratio and number of detected metastases compared with gadobenate, at both equal (0.1 mmol/kg) dose and 20% lower Gd dose (0.08 mmol/kg). Tumor detection was higher after gadopiclenol at the dose of 0.1 mmol/kg compared with 0.08 mmol/kg., Competing Interests: Conflicts of interest and sources of funding: All authors are Guerbet employee. Banque Publique d'Investissement (France)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: After the administration of gadolinium-based contrast agents (GBCAs), residual gadolinium (Gd) has been detected in a few distinct morphological structures of the central nervous system (CNS). However, a systematic, comprehensive, and quantitative analysis of the spatial Gd distribution in the entire brain is not yet available. The first aim of this study is to provide this analysis in healthy rats after administration of high GBCA doses. The second aim is to assess the spatial distributions and possible Gd colocalizations of endogenous iron (Fe), manganese (Mn), and phosphorus (P). In addition, the presence of Gd in proximity to blood vessels was assessed by immunohistochemistry., Materials and Methods: Male rats were randomly assigned to 3 groups (n = 3/group): saline (control), gadodiamide (linear GBCA), and gadobutrol (macrocyclic GBCA) with cumulative Gd doses of 14.4 mmol/kg of body mass. Five weeks after the last administration, the brains were collected and cryosectioned. The spatial distributions of Gd, Fe, Mn, and P were analyzed in a total of 130 sections, each covering the brain in 1 of the 3 perpendicular anatomical orientations, using laser ablation coupled with inductively coupled plasma mass spectrometry. Quantitative spatial element maps were generated, and the concentrations of Gd, Fe, and Mn were measured in 31 regions of interest covering various distinct CNS structures. Correlation analyses were performed to test for possible colocalization of Gd, Fe, and Mn. The spatial proximity of Gd and blood vessels was studied using metal-tagged antibodies against von Willebrand factor with laser ablation coupled with inductively coupled plasma mass spectrometry., Results: After administration of linear gadodiamide, high Gd concentrations were measured in many distinct structures of the gray matter. This involved structures previously reported to retain Gd after linear GBCA, such as the deep cerebellar nuclei or the globus pallidus, but also structures that had not been reported so far including the dorsal subiculum, the retrosplenial cortex, the superior olivary complex, and the inferior colliculus. The analysis in all 3 orientations allowed the localization of Gd in specific subregions and layers of certain structures, such as the hippocampus and the primary somatosensory cortex. After macrocyclic gadobutrol, the Gd tissue concentration was significantly lower than after gadodiamide. Correlation analyses of region of interest concentrations of Gd, Fe, and Mn revealed no significant colocalization of Gd with endogenous Fe or Mn in rats exposed to either GBCA. Immunohistochemistry revealed a colocalization of Gd traces with vascular endothelium in the deep cerebellar nuclei after gadobutrol, whereas the majority of Gd was found outside the vasculature after gadodiamide., Conclusions: In rats exposed to gadodiamide but not in rats exposed to gadobutrol, high Gd concentrations were measured in various distinct CNS structures, and structures not previously reported were identified to contain Gd, including specific subregions and layers with different cytoarchitecture and function. Knowledge of these distinct spatial patterns may pave the way for tailored functional neurological testing. Signs for the localization of the remaining Gd in the vascular endothelium were prominent for gadobutrol but not gadodiamide. The results also indicate that local transmetalation with endogenous Fe or Mn is unlikely to explain the spatial patterns of Gd deposition in the brain, which argues against a general role of these metals in local transmetalation and release of Gd ions in the CNS., Competing Interests: Conflicts of interest and sources of funding: T.F., J.B., and H.P. are employees of Bayer AG. L.H. was an employee of Bayer AG during part of the investigations., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The ideal contrast agent for imaging patients with hepatocellular carcinoma (HCC) following locoregional therapies (LRT) remains uncertain. We conducted a meta-analysis to assess the diagnostic performance of magnetic resonance imaging with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (EOB-MRI) in detecting residual or recurrence HCC following LRT., Methods: Original studies comparing the diagnostic performance of ECA-MRI and EOB-MRI were systematically identified through comprehensive searches in PubMed, EMBASE, Cochrane Library and Web of Science databases. The pooled sensitivity and specificity of ECA-MRI and EOB-MRI were calculated using a bivariate-random-effects model. Subgroup-analyses were conducted to compare the diagnostic performance of ECA-MRI and EOB-MRI according to different variables. Meta-regression analysis was employed to explore potential sources of study heterogeneity., Results: A total of 15 eligible studies encompassing 803 patients and 1018 lesions were included. Comparative analysis revealed no significant difference between ECA-MRI and EOB-MRI in the overall pooled sensitivity (87% vs. 79%) and specificity (92% vs. 96%) for the detection of residual or recurrent HCC after LRT (P = 0.41), with comparable areas under the HSROC of 0.95 and 0.92. Subgroup analyses indicated no significant diagnostic performance differences between ECA-MRI and EOB-MRI according to study design, type of LRT, most common etiology of liver disease, baseline lesion size, time of post-treated examination and MRI field strength (All P > 0.05)., Conclusion: ECA-MRI exhibited overall comparable diagnostic performance to EOB-MRI in assessing residual or recurrent HCC after LRT., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale and Objectives: Microvascular invasion (MVI) is an important risk factor in hepatocellular carcinoma (HCC), but it can only be determined through histopathological results. The aim of this study was to develop and validate a nomogram for preoperative prediction MVI in HCC using gadoxetic acid-enhanced magnetic resonance imaging (MRI) and intravoxel incoherent motion imaging (IVIM)., Materials and Methods: From July 2017 to September 2022, 148 patients with surgically resected HCC who underwent preoperative gadoxetic acid-enhanced MRI and IVIM were included in this retrospective study. Clinical indicators, imaging features, and diffusion parameters were compared between the MVI-positive and MVI-negative groups using the chi-square test, Mann-Whitney U test, and independent sample t test. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance in predicting MVI. Univariate and multivariate analyses were conducted to identify the significant clinical-radiological variables associated with MVI. Subsequently, a predictive nomogram that integrates clinical-radiological risk factors and diffusion parameters was developed and validated., Results: Serum alpha-fetoprotein level, tumor size, nonsmooth tumor margin, peritumoral hypo-intensity on hepatobiliary phase (HBP), apparent diffusion coefficient value and D value were statistically significant different between MVI-positive group and MVI-negative group. The results of multivariate analysis identified tumor size (odds ratio [OR], 0.786; 95% confidence interval [CI], 0.675-0.915; P < .01), nonsmooth tumor margin (OR, 2.299; 95% CI, 1.005-5.257; P < .05), peritumoral hypo-intensity on HBP (OR, 2.786; 95% CI, 1.141-6.802; P < .05) and D (OR, 0.293; 95% CI,0.089-0.964; P < .05) was the independent risk factor for the status of MVI. In ROC analysis, the combination of peritumoral hypo-intensity on HBP and D demonstrated the highest area under the curve value (0.902) in prediction MVI status, with sensitivity 92.8% and specificity 87.7%. The nomogram exhibited excellent predictive performance with C-index of 0.936 (95% CI 0.895-0.976) in the patient cohort, and had well-fitted calibration curve., Conclusion: The nomogram incorporating clinical-radiological risk factors and diffusion parameters achieved satisfactory preoperative prediction of the individualized risk of MVI in patients with HCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99m Tc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies., Methods: Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL)., Results: Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046)., Conclusion: LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99m Tc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE., Relevance Statement: MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction., Key Points: • Both MRI and HBS can assess liver function after RE. • Liver enhancement on MRI correlates with mebrofenin uptake on HBS. • MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction., (© 2024. The Author(s).)

Purpose: To construct a gadoxetic acid-enhanced MRI (EOB-MRI) -based multivariable model to predict Ki-67 expression levels in hepatocellular carcinoma (HCC) using LI-RADS v2018 imaging features., Methods: A total of 121 patients with HCC who underwent EOB-MRI were enrolled in this study. The patients were divided into three groups according to Ki-67 cut-offs: Ki-67 ≥ 20% (n = 86) vs. Ki-67 < 20% (n = 35); Ki-67 ≥ 30% (n = 73) vs. Ki-67 < 30% (n = 48); Ki-67 ≥ 50% (n = 45) vs. Ki-67 < 50% (n = 76). MRI features were analyzed to be associated with high Ki-67 expression using logistic regression to construct multivariable models. The performance characteristic of the models for the prediction of high Ki-67 expression was assessed using receiver operating characteristic curves., Results: The presence of mosaic architecture (p = 0.045), the presence of infiltrative appearance (p = 0.039), and the absence of targetoid hepatobiliary phase (HBP, p = 0.035) were independent differential factors for the prediction of high Ki-67 status (≥ 50% vs. < 50%) in HCC patients, while no features could predict high Ki-67 status with thresholds of 20% (≥ 20% vs. < 20%) and 30% (≥ 30% vs. < 30%) (p > 0.05). Four models were constructed including model A (mosaic architecture and infiltrated appearance), model B (mosaic architecture and targetoid HBP), model C (infiltrated appearance and targetoid HBP), and model D (mosaic architecture, infiltrated appearance and targetoid HBP). The model D yielded better diagnostic performance than the model C (0.776 vs. 0.669, p = 0.002), but a comparable AUC than model A (0.776 vs. 0.781, p = 0.855) and model B (0.776 vs. 0.746, p = 0.076)., Conclusions: Mosaic architecture, infiltrated appearance and targetoid HBP were sensitive imaging features for predicting Ki-67 index ≥ 50% and EOB-MRI model based on LI-RADS v2018 features may be an effective imaging approach for the risk stratification of patients with HCC before surgery., (© 2024. The Author(s).)

This study aimed to compare the detection of neuroendocrine tumor liver metastases (NLMs) in hepatobiliary-specific contrast-enhanced MRI (pMR) versus 68 Ga-DOTATATE PET/CT (DT-PET). This retrospective study cohort included 30 patients with well-differentiated neuroendocrine tumors who underwent both DT-PET and pMR. Two readers independently assessed NLMs count, SUVmax on DT-PET, and signal characteristics on pMR. A consensus review by two additional readers resolved discrepancies between the modalities. Results showed concordance between DT-PET and pMR NLM count in 14/30 patients (47%). pMR identified more NLMs in 12/30 patients (40%), of which 4 patients showed multiple deposits on pMR but only 0-1 lesions on DT-PET. DT-PET detected more in 4/30 patients (13%). Overall, pMR detected more metastases than DT-PET ( p = 0.01). Excluding the four outliers, there was excellent agreement between the two methods (ICC: 0.945, 95%CI: 0.930, 0.958). Notably, pMR had a higher NLM detection rate than DT-PET, with correlations found between lesion size on pMR and DT-PET detectability, as well as diffusion restriction on pMR and SUVmax on DT-PET. In conclusion, in consecutive patients with well-differentiated NETs, the detection rate of NLM is higher with pMR than with DT-PET. However, when excluding patients whose tumors do not overexpress somatostatin receptors (13% of the cohort), high concordance in the detection of NLM is observed between DT PET and pMR.

This letter to the editor is a commentary on a study titled "Liver metastases: The role of magnetic resonance imaging." Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma (HCC) is the key to achieving precise diagnosis and treatment and improving prognosis. This review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases, describes its main imaging features, and focuses on the added value of the latest imaging tools (such as T1 weighted in phase imaging, T1 weighted out of phase imaging; diffusion-weighted imaging, T2 weighted imaging). In this study, I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: This study aimed to verify whether the Liver-to-portal Ratio (LPR) can assess the adequacy of the Hepatobiliary Phase (HBP) for patients with different liver functions., Methods: A total of 125 patients were prospectively enrolled in the study and graded into the non-cirrhosis group (45), Child-Pugh A group (40), and Child- Pugh B/C group (40). The LPR on HBP was calculated after eight HBPs were obtained within 5-40 minutes. The adequate HBP was determined according to the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus statement. The differences in LPR and lesions' conspicuity between 10-min HBP and adequate HBP were analyzed by paired t-test and Wilcoxon signed-rank test, respectively. The chisquare test was used to test the difference in proportion with LPR larger than 1.462 between 10-min HBP and adequate HBP., Results: The differences in LPR and lesions' conspicuity between 10-min HBP and adequate HBP were significant in Child-Pugh A and Child-Pugh B/C groups (P < 0.05), except for the non-cirrhosis group (P > 0.05). The differences in proportion with LPR larger than 1.462 between 10-min HBP and adequate HBP were not statistically significant in all groups (all P > 0.05)., Conclusion: The adequate HBP obtained according to the 2016 ESGAR consensus statement could provide larger LPR and better lesions' conspicuity than 10- min HBP, especially for cirrhotic patients; however, the efficacy of using an LPR cutoff of 1.462 as the standard of the adequate HBP may be compromised in patients with cirrhosis.

Purpose: To explore the potential of diffusion kurtosis imaging (DKI) for assessing the degree of liver injury in a paracetamol-induced rat model and to simultaneously investigate the effect of intravenous gadoxetate on DKI parameters., Methods: Paracetamol was used to induce hepatoxicity in 39 rats. The rats were pathologically classified into 3 groups: normal (n=11), mild necrosis (n=18), and moderate necrosis (n=10). DKI was performed before and, 15 min, 25 min, and 45 min after gadoxetate administration. Repeated-measures ANOVA with Tukey's multiple comparison test was used to investigate the effect of gadoxetate on mean diffusivity (MD) and mean diffusion kurtosis (MK) and to assess the differences in MD and MK among the three groups. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of the MD values when discriminating between the necrotic groups., Results: Gadoxetate had no significant effect on either the MD or the MK, and the effect size was small. The MD in the moderate necrosis group was significantly lower than that in the other two groups (F = 13.502, p < 0.001; η2 = 0.428 [95% CI: 0.082-0.637]), while the MK did not significantly differ among the three groups (F = 2.702, p = 0.081; η2 = 0.131 [95% CI: 0.001-0.4003]). The AUCs of MD for discriminating the moderate necrosis or normal group from the other groups were 0.921 (95% CI: 0.832-1.000) and 0.831 (95% CI: 0.701-0.961), respectively., Conclusion: It would be better to measure the MD and MK before gadoxetate injection. MD showed potential for assessing the degree of liver necrosis in a paracetamol-induced liver injury rat model.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The offspring of CD-1 mice exposed during pregnancy to one of seven gadolinium-based contrast agents (GBCAs) were evaluated for potential effects on postnatal development and behavior. The GBCAs, comprising four linear (gadopentetate dimeglumine, gadodiamide, gadobenate dimeglumine, and gadoxetate disodium) and three macrocyclic (gadoterate meglumine, gadoteridol, and gadobutrol), were administered via intravenous injection once daily from Gestation Day 6 through 17 following confirmed mating (Day 0) at doses of at least twice the human equivalent recommended clinical dose (i.e., 0.63 mmol Gd/kg for gadoxetate disodium and 2.5 mmol Gd/kg for the other GBCAs). All dams were allowed to deliver naturally. F0 generation females were monitored for maternal toxicity and gadolinium (Gd) levels in blood and brain. Offspring were evaluated for Gd levels in blood and brain at birth and on Day 70 postpartum. F1 generation mice were evaluated for survival and growth preweaning. Selected pups/litter were evaluated postweaning for sexual maturation, growth, and behavior. Gd was quantifiable in the brain of the F1 offspring on PND 1, with levels declining over time. There was no long-term effect of any GBCA on the growth and development of any offspring. There was no impact on neurodevelopment, as assessed by brain histology and validated neurobehavioral tests, including a battery of functional observational tests, motor activity, and learning and memory as evaluated in the Morris water maze., Conclusion: At the end of the postweaning period, the highest dose tested was considered the no-observable-adverse-effect level (NOAEL) in the F0 and F1 offspring for all tested GBCAs., (© 2023 Charles River Laboratories, Inc., Horsham, PA. Birth Defects Research published by Wiley Periodicals LLC.)

Background: Hepatic hemangiomas are the most common benign liver tumors. It is important to know the imaging features of hemangiomas on gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI)., Purpose: To evaluate the qualitative and quantitative imaging features of hemangiomas on GA-enhanced MRI, and to compare imaging features of hemangiomas with and without pseudo-washout sign (PWS)., Material and Methods: We retrospectively included 93 cases of hemangioma that underwent GA-enhanced MRI. The presence of an enhancement pattern in the arterial phase (AP) and PWSs in the transitional phase (TP) were evaluated. Signal-to-norm ratios (SI Norm ) of hemangiomas, liver parenchyma, and portal vein (PV) as well as contrast-to-norm ratio (C Norm ) were assessed. Additionally, hemangiomas with and without PWSs were defined as two separate subgroups, and imaging features were compared., Results: Of the 93 cases of hemangiomas, 49 (52.6%) had PWSs in the TP. The mean SI Norms of hemangiomas showed the highest value in the AP ( P  < 0.05). The mean C Norms showed positive values in the AP, and gradually decreased ( P  < 0.05). Hemangiomas with PWSs were significantly rapidly enhanced and smaller in size ( P  < 0.05), and the mean SI Norms was lower in the TP ( P  = 0.023). While the mean C Norms showed a significant difference in the AP between subgroups ( P  < 0.001), the enhancement pattern was equal to that of the PV., Conclusion: When evaluating GA-enhanced MRI, radiologists should utilize quantitative measures in addition to qualitative assessment and should be aware that SI matching with PV in all phases can be a distinguishing finding in the diagnosis of hemangioma., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Accurately predicting the hepatocellular carcinoma (HCC) grade may facilitate the rational selection of treatment strategies. The diagnostic efficacy of the combination of Gadolinium ethoxybenzy diethylenetriamine pentaacetic (Gd-EOB-DTPA) enhancement T1 mapping and apparent diffusion coefficient (ADC) values in predicting HCC grade needs further validation., Objectives: This study aimed to assess the capacity of Gd-EOB-DTPA-enhanced T1 mapping and ADC values, both individually and in combination, to discriminate between different grades of HCC., Materials and Methods: From July 2017 to February 2020, 96 patients (male, 83; mean age, 53.67 years; age range, 29-71 years) clinically diagnosed with HCC were included in the present study. All patients underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI, including T1 mapping sequence) before surgery or biopsy. All the patients were categorized into 3 groups according to the pathological results (including 24 cases of well-differentiated HCCs, 59 cases of moderately differentiated HCCs, 13 cases of and poorly differentiated HCCs). The mean Gd-EOB-DTPA enhanced T1 values (&#916;T1=[(T1pre-T1post)/T1pre]×100%) and ADC values between different grading groups of HCC were calculated and compared. The area under the characteristics curve (AUC), the diagnostic threshold, sensitivity, and specificity of &#916;T1 and ADC for differential diagnosis were analyzed., Results: Mean &#916;T1 was 58% for well-differentiated HCCs, 50% for moderately-differentiated HCCs, and 43% for poorly-differentiated HCCs. &#916;T1 showed statistical differences between the groups (P<0.001). The mean ADC values of the 3 groups were 1.11×10-3 mm2/s, 0.91×10-3 mm2/s, and 0.80×10-3mm2/s, respectively. ADC showed statistical differences between the groups (P<0.001). In discriminating well- differentiated group from the moderately differentiated group, the AUC of &#916;T1 was 0.751 (95% CI: 0.642, 0.859), the AUC of ADC was 0.782 (95% CI: 0.671, 0.894), the AUC of combined model was 0.811 (95% CI: 0.709, 0.914). In discriminating the poorly differentiated group from the moderately differentiated group, the AUC of &#916;T1 was 0.768 (95% CI: 0.634, 0.902), the AUC of ADC was 0.754 (95% CI: 0.603, 0.904), and the AUC of the combined model was 0.841 (95% CI: 0.729, 0.953)., Conclusion: Gd-EOB-DTPA enhanced T1 mapping, and ADC values have complementary effects on the sensitivity and specificity for identifying different HCC grades. A combined model of Gd-EOB-DTPA-enhanced MRI T1 mapping and ADC values could improve diagnostic performance for predicting HCC grades.

Objective: To investigate the feasibility of image characteristics and radiomics combined with machine learning based on Gd-EOB-DTPA-enhanced MRI for functional liver reserve assessment in cirrhotic patients., Materials and Methods: 123 patients with cirrhosis were retrospectively analyzed; all our patients underwent pre-contrast MRI, triphasic (arterial phase, venous phase, equilibrium phase) Gd-EOB-DTPA dynamic enhancement and hepatobiliary phase (20 minutes delayed). The relative enhancement (RE) of the patient's liver, the liver-spleen signal ratio in the hepatobiliary phase (SI liver/ spleen), the liver-vertical muscle signal ratio in the hepatobiliary phase (SI liver/ muscle), the bile duct signal intensity contrast ratio (SIR), and the radiomics features were evaluated. The support vector machine (SVM) was used as the core of machine learning to construct the liver function classification model using image and radiomics characteristics, respectively., Results: The area under the curve was the largest in SIR to identify Child-Pugh group A versus Child-Pugh group B+C in the image characteristics, AUC = 0.740, and Perc. 10% to identify Child-Pugh group A versus Child-Pugh group B+C in the radiomics characteristics, AUC = 0.9337. The efficacy of the SVM model constructed using radiomics characteristics was better, with an area under the curve of 0.918, a sensitivity of 95.45%, a specificity of 80.00%, and an accuracy of 89.19%., Conclusion: The image and radiomics characteristics based on Gd-EOB-DTPA-enhanced MRI can reflect liver function, and the model constructed based on radiomics characteristics combined with machine learning methods can better assess functional liver reserve., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: The aim of this study was to formally investigate the apparent variation in lesion size of hepatic metastatic lesions from colorectal cancer on hepatobiliary phase (HBP) and dual contrast images of magnetic resonance imaging performed with both hepatobiliary and extracellular contrast agents., Methods: Patients with known colorectal carcinoma who had undergone dual contrast liver magnetic resonance imaging were identified in our institutional database. Metastatic lesions were measured semiautomatically on both HBP and dual contrast images with a custom software tool that automatically identifies the lesion edge and thereby the lesion diameter. Lesion measurements from both sets of images were compared with a Student t test and Bland-Altman analysis. Lesions were also measured on both HBP and dual contrast images by 2 fellowship-trained abdominal radiologists. Measurements from the software and radiologists were compared with a Student t test and Bland-Altman analysis; interreader agreement was evaluated with the intraclass correlation coefficient., Results: A total of 70 liver lesions in 39 patients was identified. Software-based measurements were significantly larger on HBP than dual contrast images ( P < 0.001), with a mean lesion size of 10.9 ± 4.2 mm for HBP and 10.5 ± 4.2 mm for dual contrast measurements. Radiologist-based measurements showed a similar trend, with HBP measurements being significantly larger than dual contrast measurements ( P < 0.001). Bland-Altman analysis indicated a mean bias ± 2 SD of +0.4 ± 1.6 mm for software-based measurements and +0.9 ± 2.9 mm and +0.7 ± 2.1 mm for readers 1 and 2, respectively. The intraclass correlation coefficient for interreader agreement was 0.9., Conclusions: Both software-based and radiologist-based measurements of colorectal cancer liver metastases are significantly larger on HBP than dual contrast images. Based on these findings, we recommend that longitudinal assessment be performed consistently on either HBP or dual contrast phases to avoid introduction of avoidable variability., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Since its introduction in the worldwide medical market, gadoxetic acid has attracted considerable interest. The year 2023 marks the 15th anniversary of the introduction of gadoxetic acid in Japan. Gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) is the predominantly performed contrast MRI examination for the liver. Its most essential characteristic, namely, the hepatobiliary phase, revolutionized the clinical management of liver disease. Gadoxetic acid-enhanced MRI is currently the most efficient method for focal liver lesion detection and analysis. Meta-analyses demonstrated its excellent effectiveness for the diagnosis of hepatocellular carcinoma and liver metastases. Owing to the extensive usage of gadoxetic acid, a hepatobiliary phase hypointense nodule without arterial phase hyperenhancement is well documented. The existence of such nodules may be a sign of hypervascular hepatocellular carcinoma in nodules and other areas in the liver. Apart from its role in tumor identification and characterization, GA-MRI can help assess response to therapy and liver fibrosis. Therefore, it is proposed to use gadoxetic acid as the first option for MRI of the liver in the majority of patients. The efficacy of gadoxetic acid surpasses its disadvantages, rendering this contrast agent the preferred choice for routine MRI of the liver. The clinical use of GA-MRI is discussed in this review article., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Despite improvements in operative techniques and perioperative care, post-hepatectomy liver failure (PHLF) remains the most serious cause of morbidity and mortality after surgery, and several risk factors have been identified to predict PHLF. Although volumetric assessment using imaging contributes to surgical simulation by estimating the function of future liver remnants in predicting PHLF, liver function is assumed to be homogeneous throughout the liver. The combination of volumetric and functional analyses may be more useful for an accurate evaluation of liver function and prediction of PHLF than only volumetric analysis. Gadoxetic acid is a hepatocyte-specific magnetic resonance (MR) contrast agent that is taken up by hepatocytes via the OATP1 transporter after intravenous administration. Gadoxetic acid-enhanced MR imaging (MRI) offers information regarding both global and regional functions, leading to a more precise evaluation even in cases with heterogeneous liver function. Various indices, including signal intensity-based methods and MR relaxometry, have been proposed for the estimation of liver function and prediction of PHLF using gadoxetic acid-enhanced MRI. Recent developments in MR techniques, including high-resolution hepatobiliary phase images using deep learning image reconstruction and whole-liver T1 map acquisition, have enabled a more detailed and accurate estimation of liver function in gadoxetic acid-enhanced MRI., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

In 2014, for the first time, visible hyperintensities on unenhanced T1-weighted images in the nucleus dentatus and globus pallidus of the brain were associated with previous Gadolinium-based contrast agent (GBCA) injections and gadolinium deposition in patients with normal renal function. This led to a frenzy of retrospective studies with varying methodologies that the European Society of Magnetic Resonance in Medicine and Biology Gadolinium Research and Educational Committee (ESMRMB-GREC) summarised in 2019. Now, after 10 years, the members of the ESMRMB-GREC look backward and forward and review the current state of knowledge of gadolinium retention and deposition. CLINICAL RELEVANCE STATEMENT: Gadolinium deposition is associated with the use of linear GBCA but no clinical symptoms have been associated with gadolinium deposition. KEY POINTS : • Traces of Gadolinium-based contrast agent-derived gadolinium can be retained in multiple organs for a prolonged time. • Gadolinium deposition is associated with the use of linear Gadolinium-based contrast agents. • No clinical symptoms have been associated with gadolinium deposition., (© 2023. The Author(s).)

Objective: The assessment of liver cancer lesion characteristics mainly relies on multi-row spiral computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT suffers from a series of problems, such as low soft tissue contrast and large tumor boundary errors, which lead to its limited practical application value in liver cancer. In contrast, Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI has better soft-tissue contrast than MDCT and increases the clarity of liver cancer lesions. To investigate the differences between MDCT and Gd-EOB-DTPA-enhanced MRI in managing patients with hepatocellular liver cancer., Methods: A total of 80 patients diagnosed with hepatocellular carcinoma of the liver, who received treatment at our hospital between September 2020 and September 2022, were included in this study. These patients were evenly divided into two groups: the observation group and the control group, with 40 cases in each. The aim of this study was to compare the differences in signal indices of hepatobiliary stage between the two groups in patients with hepatocellular carcinoma., Results: A total of 89 cancer nodules were detected in patients by MDCT, and 109 cancer nodules were detected in patients by Gd-EOB-DTPA-enhanced MRI. When the number of nodules detected by both imaging modalities was statistically analyzed, the differences in the number of hepatocellular carcinoma (HCC) nodules detected by MDCT and Gd-EOB-DTPA-enhanced MRI were statistically significant (P < .05). Further analysis of the data by single cancer nodule, multiple cancer nodules, and cancer nodule size showed that the difference between the two imaging modalities was statistically significant (P < .05) in the diagnosis of patients with a single liver cancer nodule or multiple liver cancer nodules (94.8% vs.81.3%). The difference in the comparison was statistically significant (P < .05)., Conclusion: Gd-EOB-DTPA-enhanced MRI demonstrates superior diagnostic efficacy in detecting small hepatocellular carcinoma, offers improved staging capabilities for hepatocellular carcinoma, and provides more precise guidance for treatment planning.Consequently, Gd-EOB-DTPA-enhanced MRI exhibits exceptional diagnostic value and serves as a valuable tool for guiding treatment decisions in patients with hepatocellular carcinoma.

Background The presence of gadolinium traces in the skin after administration of gadolinium-based contrast agents (GBCAs) raised safety concerns regarding a potential association with small fiber neuropathy (SFN). Purpose To investigate signs of SFN in rat foot pads by quantification of the intraepidermal nerve fiber density (IENFD) after multiple GBCA administrations and to evaluate gadolinium concentration, chemical species, and clearance. Materials and Methods Fifty rats received eight intravenous injections of either gadodiamide, gadobutrol, gadoterate, gadoteridol (8 × 0.6 mmol per kilogram of body weight), or saline (1.2 mL per kilogram of body weight), within 2 weeks and were sacrificed 5 days or 5 weeks after the last injection. IENFD was determined with protein gene product (PGP) 9.5 immunofluorescent staining and blinded and automated image analysis. The gadolinium and GBCA concentrations were measured with inductively coupled plasma mass spectrometry (ICP-MS), laser ablation ICP-MS, and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). P values were calculated using linear contrasts of model analysis. Results The IENFD (measured as geometric mean [SD] and in number of nerve fibers per millimeter of epidermis) was not significantly altered after 5 days (saline, 8.4 [1.1]; gadobutrol, 9.7 [1.2]; gadoterate, 9.2 [1.2]; gadoteridol, 9.9 [1.3]; gadodiamide, 10.5 [1.2]) or 5 weeks (saline, 19.7 [1.4]; gadobutrol, 16.4 [1.6]; gadoterate, 14.3 [1.6]; gadoteridol, 22.2 [1.8]; gadodiamide, 17.9 [1.4]). Gadolinium skin concentrations were highest for gadodiamide after 5 days (16.0 nmol/g [1.1]) and 5 weeks (10.6 nmol/g [1.2], -33%). Macrocyclic agents were lower at 5 days (gadoteridol, 2.6 nmol/g [1.2]; gadobutrol, 2.7 nmol/g [1.1]; and gadoterate, 2.3 nmol/g [1.2]) and efficiently cleared after 5 weeks (gadoteridol, -95%; gadobutrol and gadoterate, -96%). The distribution of gadolinium and IENF did not visually overlap. For macrocyclic agents, gadolinium was found in sweat glands and confirmed to be intact chelate. Conclusion There were no signs of SFN in rat foot pads using multiple dosing regimens at two time points after administration of GBCAs. Macrocyclic GBCAs exhibited lower levels of gadolinium in the skin and were effectively eliminated within 5 weeks compared with linear gadodiamide, and intact macrocyclic GBCA was detected in sweat glands. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Clement in this issue.

Objective: To compare therapeutic outcomes after liver transplantation (LT) between hepatocellular carcinomas (HCC) with low and high risk for microvascular invasion (MVI) within the Milan criteria evaluated preoperatively., Methods: Eighty patients with a single HCC who underwent LT as the initial therapy between 2008 and 2017 were included from two tertiary referral medical centers in a HBV-predominant population. A preoperative MVI-risk model was used to identify low- and high-risk patients. Recurrence-free survival (RFS) after LT between the two risk groups was compared using Kaplan-Meier curves with the log-rank test. Prognostic factors for RFS were identified using a multivariable Cox hazard regression analysis., Results: Eighty patients were included (mean age, 51.8 years +/- 7.5 [standard deviation], 65 men). Patients were divided into low-risk (n = 64) and high-risk (n = 16) groups for MVI. The RFS rates after LT were significantly lower in the MVI high-risk group compared to the low-risk group at 1 year (75.0% [95% CI: 56.5-99.5%] vs. 96.9% [92.7-100%], p = 0.048), 3 years (62.5% [42.8-91.4%] vs. 95.3% [90.3-100%], p = 0.008), and 5 years (62.5% [42.8-91.4%] vs. and 95.3% [90.3-100%], p = 0.008). In addition, multivariable analysis showed that MVI high risk was the only significant factor for poor RFS (p = 0.016)., Conclusion: HCC patients with a high risk of MVI showed significantly lower RFS after LT than those without. This model could aid in selecting optimal candidates in addition to the Milan criteria when considering upfront LT for patients with HCC if alternative treatment options are available., Clinical Relevance Statement: High risk for microvascular invasion (MVI) in hepatocellular carcinoma patients lowered recurrence-free survival after liver transplantation, despite meeting the Milan criteria. Identifying MVI risk could aid candidate selection for upfront liver transplantation, particularly if alternative treatments are available., Key Points: • A predictive model-derived microvascular invasion (MVI) high- and low-risk groups had a significant difference in the incidence of MVI on pathology. • Recurrence-free survival after liver transplantation (LT) for single hepatocellular carcinoma (HCC) within the Milan criteria was significantly different between the MVI high- and low-risk groups. • The peak incidence of tumor recurrence was 20 months after liver transplantation, probably indicating that HCC with high risk for MVI had a high risk of early (≤ 2 years) tumor recurrence., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC)., Materials and Methods: In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value < .05 was considered statistically significant. The display efficiency of the LLC between Gd-BOPTA and Gd-EOB-DTPA for HCC features was evaluated by receiver operating characteristic (ROC) curve analysis., Results: Between Gd-BOPTA and Gd-EOB-DTPA, significant differences were observed regarding the display efficiency for capsule enhancement and the LLC in the AP/PVP/DP ( P  < .05), but there was no significant difference regarding the LLC in the TP/HBP. Both Gd-BOPTA and Gd-EOB-DTPA had good display efficiency in each phase (AUC min  > 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950)., Conclusion: Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: We aimed to modify the LR-5 strategy to improve the diagnostic sensitivity for hepatocellular carcinoma (HCC) in high-risk patients while maintaining specificity. Methods: This study retrospectively analyzed 412 patients with 445 liver observations who underwent preoperative gadolinium ethoxybenzyl DTPA (GD-EOB-DTPA)-enhanced MRI followed by surgical procedures or biopsies. All observations were classified according to LI-RADS v2018, and the classifications were adjusted by modifying major features (MF)(substituting threshold growth with a more HCC-specific ancillary features (AF): presence of blood products within the mass, arterial phase hyperenhancement (APHE) was interpreted with hypointensity on precontrast imaging- isointensity in arterial phase (AP) and extending washout to transitional phase (TP)(2 min)). The specificity, sensitivity, and positive predictive value (PPV) were assessed to compare LR-5 (definitely HCC) diagnostic efficacy between LI-RADS version 2018 and modified LI-RADS. Results: Apart from nonenhancing "capsule", the interreader agreement of MFs and HCC-specific AFs between the two readers reached substantial or excellent ranges (κ values ranging from 0.631 to 0.911). According to LI-5 v2018, the specificity, sensitivity and PPV of HCC were 90.74%, 82.35%, and 98.17%, respectively. Based on a more HCC-specific AF, signal intensity in AP and TP (2 min), the sensitivity of the three modified strategies were 86.19%, 93.09%, 96.67% (P < .05)), while maintaining high specificity and PPV rates at 88.89% and 98.25% (P > .05) Conclusion: Further investigation into the efficacy of threshold growth as a MF is warranted. By utilizing GD-EOB-DTPA-enhanced MRI, enhancing the sensitivity of the modified LR-5 category may be achieved without compromising specificity and PPV in diagnosing HCC among high-risk patients., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Single cell-inductively coupled plasma-mass spectrometry (sc-ICP-MS) was used in this study as a valuable tool to assess the species-dependent uptake of metallopharmaceuticals into algal cells. Chlamydomonas reinhardtii algae were incubated for 24 h with four Gadolinium-based contrast agents (GBCAs) and GdCl 3 . A species dependency towards the uptake of the tested Gd species was observed. Using single cell-ICP-MS, a Gd signal corresponding to single cell events was detected for GdCl 3 and the linear GBCAs Omniscan® (Gadodiamide, Gd-DTPA-BMA) and Magnevist® (Gadodiamide, Gd-DTPA). For the macrocyclic complexes Dotarem® (Gadoteric acid, Gd-DOTA) and Gadovist® (Gadobutrol, Gd-BT-DO3A), no such Gd signal was visible. Total Gd analysis via ICP-MS confirmed the presence of Gd in the cells only after incubation with GdCl 3 and the linear GBCAs, while only small amounts of Gd were detected for the incubations with macrocyclic GBCAs. Furthermore, the results showed that more Gd is bound to cell structures or macromolecules, while smaller amounts are present in the lysate. Using hydrophilic interaction liquid chromatography (HILIC)-ICP-MS, the soluble Gd species in the lysate were analyzed to determine if the initial Gd complexes were still intact. Surprisingly, no intact GBCAs were detected in the lysates of any incubation solution, possibly due to a change in Gd speciation. Further research is needed to assess which Gd species are present in the lysate, while "free" Gd ions or adducts with cell constituents are the most likely explanation. This study highlights the need for species-dependent investigation of elements in aquatic organisms. Moreover, the uptake of linear GBCAs and their species alteration raises the question of a potential accumulation of Gd in the food chain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gadolinium-based MR cisternography has been mainly applied in clinical evaluation of cerebrospinal fluid leaking, that is conducted by intrathecal administration of contrast media. Recently, we have reported one novel technique of intrathecal targeted drug delivery with prepontine cisternal routine to treat orofacial cancer pain. The aim of this study was to examine the distribution pattern of this intrathecal drug delivery strategy. Here, we introduce one case who suffered severe orofacial pain caused by sublingual gland tumor, and successfully attenuated by prepontine cisternal administration of analgesic agents. To assess the distribution of intrathecal drugs, postoperative MR images of brain, cervical, thoracic, and lumbar segments in axial, coronal, and sagittal planes were obtained after application of gadolinium. The perfusion rate of contrast medium was set at 0.01 mmol per hour for 24 hours prior to MR scanning. In the T1-weighted images, we can identify contrast spread not only locating around the site of the intrathecal catheter tip, but also concentrated to the lateral sides. None obvious side effect was found after intrathecal injection of contrast media. Thus, our finding demonstrated the local distribution phenomenon of intrathecal drugs through prepontine cisternal access, and the bilateral perfusion pattern may provide insights underlying the analgesic mechanism of trigeminal pain provided by this novel intrathecal therapy. Gadolinium-based MR cisternography may serve as a potential tool to confirm the therapeutic effect of intrathecal targeted drug delivery via prepontine cisternal routine in orofacial pain management.

Purpose: To evaluate the reliability of signal intensity (SI) changes in the basal ganglia as a supposed indicator of gadolinium deposition in the brain after repetitive application of gadolinium-based contrast agents (GBCAs) in a pediatric neuro-oncological collective., Methods: One hundred and eight neuropediatric patients (54 male, 54 female, 0-17 years old), with repetitive GBCA-enhanced cranial MRIs between 2003 and 2017, were retrospectively analyzed. Two radiologists measured SI in the nucleus dentatus (ND), globus pallidus (GP), thalamus (T), and the pons (P). The NDP and GPT ratio were calculated. An intraclass correlation coefficient, and multiple linear regressions with subsequent stepwise backward variable selection were performed to evaluate the influence of gender, patient's age at the first MRI, time interval between the first and last MRI, linear or macrocyclic GBCAs, residual pathology, treatments, and magnet field strengths., Results: The inter-reader agreement was good for GPT and NDP in the whole collective (ICC = 0.837 and ICC = 0.793) and for children >2 years of age (ICC = 0.874 and ICC = 0.790), but poor to moderate for children ≤2 years of age (ICC = 0.397 and ICC = 0.748). The intra-reader agreement was good (ICC = 0.910 and ICC = 0.882). An SI increase was only observed for both readers in GPT (p = 0.003, or p < 0.001). None of the considered cofactors showed a consistent effect on SI changes for either readers or regions., Conclusion: Measurements of SI changes in the basal ganglia are not a reliable parameter with which to evaluate or estimate gadolinium deposition in the brain or to identify suspicious influential factors after repeated GBCA applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Hepatic lesions categorized as LR-3, LR-4, and LR-M are challenging to accurately assess and diagnose., Purpose: To combine potential clinical and/or magnetic resonance imaging (MRI) features for a more comprehensive hepatocellular carcinoma (HCC) versus non-HCC diagnosis for patients with LR-3, LR-4, and LR-M graded lesions., Methods: Data were consecutively retrieved from 82 at-risk patients with LR-3 (n = 43), LR-4 (n = 20), and LR-M (n = 23) lesions. Significant findings for the differentiation of HCC and non-HCC, including MRI features and clinical factors, were identified with univariable and multivariable analyses. The variables for a prediction model were selected through stepwise use of Akaike's Information Criterion (AIC) to build multivariable logistic regression model., Results: Serum alpha-fetoprotein (AFP) >16.2 ng/mL (odds ratio [OR] = 22.4; P  = 0.006), septum (OR = 52.1; P  = 0.011), and hepatobiliary phase (HBP) hypointensity (OR = 40.2; P  = 0.001) were confirmed as independent predictors of HCC. When combining the three predictors and mild-moderate T2 hyperintensity, the model (AIC = 50.91) showed good accuracy with a C-index of 0.948., Conclusion: In at-risk patients with LR-3, LR-4, or LR-M lesions, integrating AFP, septum, HBP hypointensity, and mild-moderate T2 hyperintensity achieved high diagnostic performance for the diagnosis of HCC., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The 10th Global Forum for Liver Magnetic Resonance Imaging was held in October 2021. The themes of the presentations and discussions at this Forum are described in detail in the review by Taouli et al (2023). The focus of this second manuscript developed from the Forum is on multidisciplinary tumor board perspectives in hepatocellular carcinoma (HCC) management: how to approach early-, mid-, and late-stage management from the perspectives of a liver surgeon, an interventional radiologist, and an oncologist. The manuscript also includes a panel discussion by multidisciplinary experts on three selected cases that explore challenging aspects of HCC management. CLINICAL RELEVANCE STATEMENT: This review highlights the importance of a multidisciplinary team approach in liver cancer patients and includes the perspectives of a liver surgeon, an interventional radiologist, and an oncologist, including illustrative case studies. KEY POINTS: • A liver surgeon, interventional radiologist, and oncologist presented their perspectives on the treatment of early-, mid-, and late-stage HCC. • Different perspectives on HCC management between specialties emphasize the importance of multidisciplinary tumor boards. • A multidisciplinary faculty discussed challenging aspects of HCC management, as highlighted by three case studies., (© 2023. The Author(s).)

Objectives: Diffusion-weighted magnetic resonance imaging (MRI) is gaining popularity as an addition to standard dynamic contrast-enhanced breast MRI. Although adding diffusion-weighted imaging (DWI) to the standard protocol design would require increased scanning-time, implementation during the contrast-enhanced phase could offer a multiparametric MRI protocol without any additional scanning time. However, gadolinium within a region of interest (ROI) might affect assessments of DWI. This study aims to determine if acquiring DWI postcontrast, incorporated in an abbreviated MRI protocol, would statistically significantly affect lesion classification. In addition, the effect of postcontrast DWI on breast parenchyma was studied., Materials and Methods: Screening or preoperative MRIs (1.5 T/3 T) were included for this study. Diffusion-weighted imaging was acquired with single-shot spin echo-echo planar imaging before and at approximately 2 minutes after gadoterate meglumine injection. Apparent diffusion coefficients (ADCs) based on 2-dimensional ROIs of fibroglandular tissue, as well as benign and malignant lesions at 1.5 T/3.0 T, were compared with a Wilcoxon signed rank test. Diffusivity levels were compared between precontrast and postcontrast DWI with weighted κ. An overall P ≤ 0.05 was considered statistically significant., Results: No significant changes were observed in ADC mean after contrast administration in 21 patients with 37 ROI of healthy fibroglandular tissue and in the 93 patients with 93 (malignant and benign) lesions. This effect remained after stratification on B 0 . In 18% of all lesions, a diffusion level shift was observed, with an overall weighted κ of 0.75., Conclusions: This study supports incorporating DWI at 2 minutes postcontrast when ADC is calculated based on b150-b800 with 15 mL 0.5 M gadoterate meglumine in an abbreviated multiparametric MRI protocol without requiring extra scan time., Competing Interests: Conflicts of interest and sources of funding: R.M.M. (research agreements: Siemens Healthineers, Bayer Healthcare, ScreenPoint Medical, Seno Medical, Koning, Medtronic, BD/Bard). The authors state that this work has not received any funding., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To explore human glymphatic dynamics in a diseased model via a noninvasive technique., Methods: Patients with reversible vasoconstriction syndrome (RCVS) presenting with blood-brain barrier disruption, i.e., para-arterial gadolinium leakage on 3-T 3-dimensional isotropic contrast-enhanced T2-fluid-attenuated inversion recovery (CE-T2-FLAIR) magnetic resonance imaging (MRI), were prospectively enrolled. Consecutive 9-min-CE-T2-FLAIR for 5-6 times (early panel) after intravenous gadolinium-based contrast agent (GBCA) administration and one time-varying deferred scan of noncontrast T2-FLAIR (delayed panel) were performed. In Bundle 1, we measured the calibrated signal intensities (cSIs) of 10 different anatomical locations. In Bundle 2, brain-wide measurements of para-arterial glymphatic volumes, means, and medians of the signal intensities were conducted. We defined mean (mCoIs) or median (mnCoIs) concentration indices as products of volumes and signal intensities., Results: Eleven subjects were analyzed. The cSIs demonstrated early increase (9 min) in perineural spaces: (cranial nerve [CN] V, p = 0.008; CN VII + VII, p = 0.003), choroid plexus (p = 0.003), white matter (p = 0.004) and parasagittal dura (p = 0.004). The volumes, mCoIs, and mnCoIs demonstrated increasing rates of enhancement after 9 to 18 min and decreasing rates after 45 to 54 min. The GBCA was transported centrifugally and completely removed within 961-1086 min after administration., Conclusions: The exogenous GBCA leaked into the para-arterial glymphatics could be completely cleared around 961 to 1086 min after administration in a human model of BBB disruption. The tracer enhancement started variously in different intracranial regions but was eventually cleared centrifugally to brain convexity, probably towards glymphatic-meningeal lymphatics exits., Clinical Relevance Statement: Glymphatic clearance time intervals and the centrifugal directions assessed by a noninvasive approach may have implications for clinical glymphatic evaluation in the near future., Key Points: • This study aimed to investigate the human glymphatic dynamics in a noninvasive diseased model. • The intracranial MR-detectable gadolinium-based contrast agents were removed centrifugally within 961 to 1086 min. • The glymphatic dynamics was demonstrable by enhancing MRI in an in vivo diseased model noninvasively., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: To investigate the long-term evolution of LR-2, LR-3 and LR-4 observations in patients with hepatitis B virus (HBV)-related cirrhosis based on LI-RADS v2018 and identify predictors of progression to a malignant category on serial gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI)., Methods: This retrospective study included 179 cirrhosis patients with untreated indeterminate observations who underwent Gd-EOB-MRI exams at baseline and during the follow-up period between June 2016 and December 2021. Two radiologists independently assessed the major features, ancillary features, and LI-RADS category of each observation at baseline and follow-up. In cases of disagreement, a third radiologist was consulted for consensus. Cumulative incidences for progression to a malignant category (LR-5 or LR-M) and to LR-4 or higher were analyzed for each index category using Kaplan‒Meier methods and compared using log-rank tests. The risk factors for malignant progression were evaluated using a Cox proportional hazard model., Results: A total of 213 observations, including 74 (34.7%) LR-2, 95 (44.6%) LR-3, and 44 (20.7%) LR-4, were evaluated. The overall cumulative incidence of progression to a malignant category was significantly higher for LR-4 observations than for LR-3 or LR-2 observations (each P < 0.001), and significantly higher for LR-3 observations than for LR-2 observations (P < 0.001); at 3-, 6-, and 12-month follow-ups, the cumulative incidence of progression to a malignant category was 11.4%, 29.5%, and 39.3% for LR-4 observations, 0.0%, 8.5%, and 19.6% for LR-3 observations, and 0.0%, 0.0%, and 0.0% for LR-2 observations, respectively. The cumulative incidence of progression to LR-4 or higher was higher for LR-3 observations than for LR-2 observations (P < 0.001); at 3-, 6-, and 12-month follow-ups, the cumulative incidence of progression to LR-4 or higher was 0.0%, 8.5%, and 24.6% for LR-3 observations, and 0.0%, 0.0%, and 0.0% for LR-2 observations, respectively. In multivariable analysis, nonrim arterial phase hyperenhancement (APHE) [hazard ratio (HR) = 2.13, 95% CI 1.04-4.36; P = 0.038], threshold growth (HR = 6.50, 95% CI 2.88-14.65; P <0.001), and HBP hypointensity (HR = 16.83, 95% CI 3.97-71.34; P <0.001) were significant independent predictors of malignant progression., Conclusion: The higher LI-RADS v2018 categories had an increasing risk of progression to a malignant category during long-term evolution. Nonrim APHE, threshold growth, and HBP hypointensity were the imaging features that were significantly predictive of malignant progression., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recent advances in systemic therapy have had major impacts on treatment strategies for hepatocellular carcinoma (HCC). The 2022 Barcelona Clinic Liver Cancer (BCLC) guidelines incorporate a new section on clinical decision-making for personalized medicine, although the first treatment suggested by the BCLC guidelines is based on solid scientific evidence. More than ever before, the appropriate treatment strategy must be selected prior to the initiation of therapy for HCC. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) is essential for liver imaging and the hepatobiliary phase (HBP) of EOB-MRI reflects the expression of organic anion transporting polypeptide (OATP) transporters. Molecules associated with OATP expression are relevant in the molecular classification of HCC subclasses, and EOB-MRI is becoming increasingly important with advances in the molecular and genetic understanding of HCC. In this review, we describe imaging findings for the pretreatment prediction of response to standard therapies for HCC based on the BCLC algorithm using the HBP of EOB-MRI, with specific attention to the molecular background of OATPs. A more complete understanding of these findings will help radiologists suggest appropriate treatments and clinical follow-ups and could lead to the development of more personalized treatment strategies in the future. CLINICAL RELEVANCE STATEMENT: In the coming era of personalized medicine, HBP of EOB-MRI reflecting molecular and pathological factors could play a predictive role in the therapeutic efficacy of HCC and contribute to treatment selection. KEY POINTS: • Imaging features of hepatobiliary phase predict treatment efficacy prior to therapy and contribute to treatment choice. • Wnt/β-catenin activation associated with organic anion transporting polypeptide expression is involved in the tumor immune microenvironment and chemo-responsiveness. • Peritumoral hypointensity of hepatobiliary phase reflecting microvascular invasion affects the therapeutic efficacy of locoregional to systemic therapy., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

The 10th Global Forum for Liver Magnetic Resonance Imaging (MRI) was held as a virtual 2-day meeting in October 2021, attended by delegates from North and South America, Asia, Australia, and Europe. Most delegates were radiologists with experience in liver MRI, with representation also from specialists in liver surgery, oncology, and hepatology. Presentations, discussions, and working groups at the Forum focused on the following themes: • Gadoxetic acid in clinical practice: Eastern and Western perspectives on current uses and challenges in hepatocellular carcinoma (HCC) screening/surveillance, diagnosis, and management • Economics and outcomes of HCC imaging • Radiomics, artificial intelligence (AI) and deep learning (DL) applications of MRI in HCC. These themes are the subject of the current manuscript. A second manuscript discusses multidisciplinary tumor board perspectives: how to approach early-, mid-, and late-stage HCC management from the perspectives of a liver surgeon, interventional radiologist, and oncologist (Taouli et al, 2023). Delegates voted on consensus statements that were developed by working groups on these meeting themes. A consensus was considered to be reached if at least 80% of the voting delegates agreed on the statements. CLINICAL RELEVANCE STATEMENT: This review highlights the clinical applications of gadoxetic acid-enhanced MRI for liver cancer screening and diagnosis, as well as its cost-effectiveness and the applications of radiomics and AI in patients with liver cancer. KEY POINTS: • Interpretation of gadoxetic acid-enhanced MRI differs slightly between Eastern and Western guidelines, reflecting different regional requirements for sensitivity vs specificity. • Emerging data are encouraging for the cost-effectiveness of gadoxetic acid-enhanced MRI in HCC screening and diagnosis, but more studies are required. • Radiomics and artificial intelligence are likely, in the future, to contribute to the detection, staging, assessment of treatment response and prediction of prognosis of HCC-reducing the burden on radiologists and other specialists and supporting timely and targeted treatment for patients., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: To evaluate the added value of threshold growth (TG) for imaging criteria for diagnosing hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI., Methods: Patients who underwent preoperative gadoxetic acid-enhanced MRI because of absence of 'definite HCC' (Liver Imaging Reporting and Data System category 5) on prior CT or MRI between January 2016 and December 2020 were retrospectively analyzed. The sensitivity and specificity for 'definite HCC' according to the criteria of the European Association for the Study of the Liver [EASL], Asian Pacific Association for the Study of the Liver [APASL], and Korean Liver Cancer Association-National Cancer Center [KLCA-NCC] were separately calculated with and without TG as a major imaging feature. The results were compared using generalized estimating equations., Results: Of 202 nodules in 154 patients, 19 % showed TG. When TG was used as a major imaging feature, the sensitivity of EASL were significantly higher than when it was not used (59.2 % vs. 51.4 %, p = 0.001), whereas the sensitivities of APASL and KLCA-NCC did not significantly differ. No significant difference was found in the specificities of the three imaging criteria when TG was used or not (p ≥ 0.16). Of 11 HCCs additionally detected when TG was added to EASL criteria, 9 showed transitional-phase or hepatobiliary-phase hypointensity without portal venous-phase washout., Conclusion: TG had added value for improving the sensitivity of EASL criteria for gadoxetic acid-enhanced MRI without extending washout to transitional-phase or hepatobiliary-phase images., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)