Clinical-Radiologic Morphology-Radiomics Model on Gadobenate Dimeglumine-Enhanced MRI for Identification of Highly Aggressive Hepatocellular Carcinoma: Temporal Validation and Multiscanner Validation.

BACKGROUND: Highly aggressive hepatocellular carcinoma (HCC) is characterized by high tumor recurrence and poor outcomes, but its definition and imaging characteristics have not been clearly described. PURPOSE: To develop and validate a fusion model on gadobenate dimeglumine-enhanced MRI for identifying highly aggressive HCC. STUDY TYPE: Retrospective. POPULATION: 341 patients (M/F = 294/47) with surgically resected HCC, divided into a training cohort (n = 177), temporal validation cohort (n = 77), and multiscanner validation cohort (n = 87). FIELD STRENGTH/SEQUENCE: 3T, dynamic contrast-enhanced MRI with T1-weighted volumetric interpolated breath-hold examination gradient-echo sequences, especially arterial phase (AP) and hepatobiliary phase (HBP, 80-100 min). ASSESSMENT: Clinical factors and diagnosis assessment based on radiologic morphology characteristics associated with highly aggressive HCCs were evaluated. The radiomics signatures were extracted from AP and HBP. Multivariable logistic regression was performed to construct clinical-radiologic morphology (CR) model and clinical-radiologic morphology-radiomics (CRR) model. A nomogram based on the optimal model was established. Early recurrence-free survival (RFS) was evaluated in actual groups and risk groups calculated by the nomogram. STATISTICAL TESTS: The performance was evaluated by receiver operating characteristic curve (ROC) analysis, calibration curves analysis, and decision curves. Early RFS was evaluated by using Kaplan-Meier analysis. A P value <0.05 was considered statistically significant. RESULTS: The CRR model incorporating corona enhancement, cloud-like hyperintensity on HBP, and radiomics signatures showed the highest diagnostic performance. The area under the curves (AUCs) of CRR were significantly higher than those of the CR model (AUC = 0.883 vs. 0.815, respectively, for the training cohort), 0.874 vs. 0.769 for temporal validation, and 0.892 vs. 0.792 for multiscanner validation. In both actual and risk groups, highly and low aggressive HCCs showed statistically significant differences in early recurrence. DATA CONCLUSION: The clinical-radiologic morphology-radiomics model on gadobenate dimeglumine-enhanced MRI has potential to identify highly aggressive HCCs and non-invasively obtain prognostic information. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Beta-Catenin-Mutated Hepatocellular Adenomas at Hepatobiliary Phase MRI: A Systematic Review and Meta-Analysis.

BACKGROUND: Beta-catenin-mutated hepatocellular adenomas (ß-HCAs) can appear iso- to hyperintense at the hepatobiliary phase (HBP) at magnetic resonance imaging (MRI). Given the relatively lower prevalence of ß-HCAs, prior studies had limited power to show statistically significant differences in the HBP signal intensity between different subtypes. PURPOSE: To assess the diagnostic performance of HBP MRI to discriminate ß-HCA from other subtypes. STUDY TYPE: Systemic review and meta-analysis. POPULATION: Ten original studies were included, yielding 266 patients with 397 HCAs (9%, 36/397 ß-HCAs and 91%, 361/397 non-ß-HCAs). FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T, HBP. ASSESSMENT: PubMed, Web of Science, and Embase databases were searched from January 1, 2000, to August 31, 2023, for all articles reporting HBP signal intensity in patients with histopathologically proven HCA subtypes. QUADAS-2 was used to assess risk of bias and concerns regarding applicability. STATISTICAL TESTS: Univariate random-effects model was used to calculate pooled estimates. Heterogeneity estimates were assessed with I2 heterogeneity index. Meta-regression (mixed-effect model) was used to test for differences in the prevalence of HBP signal between HCA groups. The threshold for statistical significance was set at P < 0.05. RESULTS: HBP iso- to hyperintensity was associated with ß-HCAs (pooled prevalence was 72.3% in ß-HCAs and 6.3% in non-ß-HCAs). Pooled sensitivity and specificity were 72.3% (95% confidence interval 54.1-85.3) and 93.7% (93.8-97.7), respectively. Specificity had substantial heterogeneity with I2 of 83% due to one study, but not for sensitivity (I2 = 0). After excluding this study, pooled sensitivity and specificity were 77.4% (59.6-88.8) and 94.1% (88.9-96.9), with no substantial heterogeneity. One study had high risk of bias for patient selection and two studies were rated unclear for two domains. DATA CONCLUSION: Iso- to hyperintensity at HBP MRI may help to distinguish ß-HCA subtype from other HCAs with high specificity. However, there was heterogeneity in the pooled estimates. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

The value of contrast-enhanced portal vein imaging at the hepatobiliary phase obtained with gadobenate dimeglumine for predicting decompensation and transplant-free survival in chronic liver disease.

OBJECTIVES: To investigate the value of contrast-enhanced portal vein imaging at the hepatobiliary phase obtained with gadobenate dimeglumine for predicting clinical outcomes in patients with chronic liver disease (CLD). METHODS: Three hundred and fourteen CLD patients who underwent gadobenate dimeglumine-enhanced hepatic magnetic resonance imaging were stratified into three groups: nonadvanced CLD (n = 116), compensated advanced CLD (n = 120), and decompensated advanced CLD (n = 78) groups. The liver-to-portal vein contrast ratio (LPC) and liver-spleen contrast ratio (LSC) at the hepatobiliary phase were measured. The value of LPC for predicting hepatic decompensation and transplant-free survival was assessed using Cox regression analysis and Kaplan-Meier analysis. RESULTS: The diagnostic performance of LPC was significantly better than LSC in evaluating the severity of CLD. During a median follow-up period of 53.0 months, the LPC was a significant predictor for hepatic decompensation (p < 0.001) in patients with compensated advanced CLD. The predictive performance of LPC was higher than that of the model for end-stage liver disease score (p = 0.006). With the optimal cut-off value, patients with LPC ≤ 0.98 had a higher cumulative incidence of hepatic decompensation than patients with LPC > 0.98 (p < 0.001). The LPC was also a significant predictive factor for transplant-free survival in patients with compensated advanced CLD (p = 0.007) and those with decompensated advanced CLD (p = 0.002). CONCLUSIONS: Contrast-enhanced portal vein imaging at the hepatobiliary phase obtained with gadobenate dimeglumine is a valuable imaging biomarker for predicting hepatic decompensation and transplant-free survival in CLD patients. KEY POINTS: • The liver-to-portal vein contrast ratio (LPC) significantly outperformed liver-spleen contrast ratio in evaluating the severity of chronic liver disease. • The LPC was a significant predictor for hepatic decompensation in patients with compensated advanced chronic liver disease. • The LPC was a significant predictor for transplant-free survival in patients with compensated and those with decompensated advanced chronic liver disease.

Comparison of Gadobenate-Enhanced MRI and Gadoxetate-Enhanced MRI for Hepatocellular Carcinoma Detection Using LI-RADS Version 2018: A Prospective Intraindividual Randomized Study.

BACKGROUND. Gadobenate and gadoxetate show different degrees of intracellular accumulation within hepatocytes, potentially impacting these agents' relative performance for hepatocellular carcinoma (HCC) diagnosis. OBJECTIVE. The purpose of this article was to perform an intraindividual comparison of gadobenate-enhanced MRI and gadoxetate-enhanced MRI for detection of HCC and to assess the impact of inclusion of hepatobiliary phase images on HCC detection for both agents. METHODS. This prospective study enrolled 126 patients (112 men, 14 women; mean age, 52.3 years) at high risk for HCC who consented to undergo two 3-T liver MRI examinations (one using gadobenate [0.05 mmol/kg], one using gadoxetate [0.025 mmol/kg]) separated by 7-14 days. The order of the two contrast agents was randomized. All examinations included postcontrast dynamic and hepatobiliary phase images (120 minutes for gadobenate, 20 minutes for gadoxetate). Three radiologists independently reviewed the gadobenate and gadoxetate examinations in separate sessions and recorded the location of detected observations. Observations were classified using LI-RADS version 2018 and using a LI-RADS modification whereby hepatobiliary phase hypointensity may upgrade observations from category LR-4 to LR-5. Observations classified as LR-5 were considered positive interpretations for HCC. Diagnostic performance for histologically confirmed HCC (n = 96) was assessed. RESULTS. Across readers, sensitivity for HCC for gadobenate versus gadoxetate was 74.0-80.2% versus 54.2-67.7% using dynamic images alone and 82.1-87.4% versus 66.3-81.1% using dynamic and hepatobiliary phase images. For HCCs measuring 1.0-2.0 cm, sensitivity for gadobenate versus gadoxetate was 61.9% (all readers) versus 38.1-57.1% using dynamic images alone and 76.2-85.7% versus 52.4-61.9% using dynamic and hepatobiliary phase images. PPV for HCC ranged from 88.6% to 97.4% across readers, agents, and image sets. CONCLUSION. Sensitivity for HCC was higher for gadobenate than for gadoxetate, whether using dynamic images alone or dynamic and hepatobiliary phase images; the improved sensitivity using gadobenate was more pronounced for small HCCs. Whereas hepatobiliary phase images improved sensitivity for both agents, sensitivity of gadobenate using dynamic images alone compared favorably with that of gadoxetate using dynamic and hepatobiliary phase images. CLINICAL IMPACT. The findings support gadobenate as a preferred agent over gadoxetate when performing liver MRI in patients at high risk for HCC.

Dose-Lowering in Contrast-Enhanced MRI of the Central Nervous System: A Retrospective, Parallel-Group Comparison Using Gadobenate Dimeglumine.

BACKGROUND: Concerns over gadolinium (Gd) retention encourage the use of lower Gd doses. However, lower Gd doses may compromise imaging performance. Higher relaxivity gadobenate may be suited to reduced dose protocols. PURPOSE: To compare 0.05 mmol/kg and 0.1 mmol/kg gadobenate in patients undergoing enhanced MRI of the central nervous system (CNS). STUDY TYPE: Retrospective, multicenter. POPULATION: Three hundred and fifty-two patients receiving 0.05 (n = 181) or 0.1 (n = 171) mmol/kg gadobenate. FIELD STRENGTH/SEQUENCES: 1.5 T and 3.0 T/precontrast and postcontrast T1-weighted spin echo/fast spin echo (SE/FSE) and/or gradient echo/fast field echo (GRE/FFE); precontrast T2-weighted FSE and T2-FLAIR. ASSESSMENT: Images of patients with extra-axial lesions at 1.5 T or any CNS lesion at 3.0 T were reviewed by three blinded, independent neuroradiologists for qualitative (lesion border delineation, internal morphology visualization, contrast enhancement; scores from 1 = poor to 4 = excellent) and quantitative (lesion-to-brain ratio [LBR], contrast-to-noise ratio [CNR]; SI measurements at regions-of-interest on lesion and normal parenchyma) enhancement measures. Noninferiority of 0.05 mmol/kg gadobenate was determined for each qualitative endpoint if the lower limit of the 95% confidence interval (CI) for the difference in precontrast + postcontrast means was above a noninferiority margin of -0.4. STATISTICAL TESTS: Student's t-test for comparison of mean qualitative endpoint scores, Wilcoxon signed rank test for comparison of LBR and CNR values; Wilcoxon rank sum test for comparison of SI changes. Tests were significant for P < 0.05. RESULTS: The mean change from precontrast to precontrast + postcontrast was significant for all endpoints. Readers 1, 2, and 3 evaluated 304, 225, and 249 lesions for 0.05 mmol/kg gadobenate, and 382, 309, and 298 lesions for 0.1 mmol/kg gadobenate. The lower limit of the 95% CI was above -0.4 for all comparisons. Significantly, higher LBR and CNR was observed with the higher dose. DATA CONCLUSION: 0.05 mmol/kg gadobenate was noninferior to 0.1 mmol/kg gadobenate for lesion visualization. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Dynamic contrast-enhanced MRI perfusion quantification in hepatocellular carcinoma: comparison of gadoxetate disodium and gadobenate dimeglumine.

OBJECTIVES: (1) To assess the quality of the arterial input function (AIF) during dynamic contrast-enhanced (DCE) MRI of the liver and (2) to quantify perfusion parameters of hepatocellular carcinoma (HCC) and liver parenchyma during the first 3 min post-contrast injection with DCE-MRI using gadoxetate disodium compared to gadobenate dimeglumine (Gd-BOPTA) in different patient populations. METHODS: In this prospective study, we evaluated 66 patients with 83 HCCs who underwent DCE-MRI, using gadoxetate disodium (group 1, n = 28) or Gd-BOPTA (group 2, n = 38). AIF qualitative and quantitative features were assessed. Perfusion parameters (based on the initial 3 min post-contrast) were extracted in tumours and liver parenchyma, including model-free parameters (time-to-peak enhancement (TTP), time-to-washout) and modelled parameters (arterial flow (Fa), portal venous flow (Fp), total flow (Ft), arterial fraction, mean transit time (MTT), distribution volume (DV)). In addition, lesion-to-liver contrast ratios (LLCRs) were measured. Fisher's exact tests and Mann-Whitney U tests were used to compare the two groups. RESULTS: AIF quality, modelled and model-free perfusion parameters in HCC were similar between the 2 groups (p = 0.054-0.932). Liver parenchymal flow was lower and liver enhancement occurred later in group 1 vs group 2 (Fp, p = 0.002; Ft, p = 0.001; TTP, MTT, all p < 0.001), while there were no significant differences in tumour LLCR (max. positive LLCR, p = 0.230; max. negative LLCR, p = 0.317). CONCLUSION: Gadoxetate disodium provides comparable AIF quality and HCC perfusion parameters compared to Gd-BOPTA during dynamic phases. Despite delayed and decreased liver enhancement with gadoxetate disodium, LLCRs were equivalent between contrast agents, indicating similar tumour conspicuity. KEY POINTS: • Arterial input function quality, modelled, and model-free dynamic parameters measured in hepatocellular carcinoma are similar in patients receiving gadoxetate disodium or gadobenate dimeglumine during the first 3 min post injection. • Gadoxetate disodium and gadobenate dimeglumine show similar lesion-to-liver contrast ratios during dynamic phases in patients with HCC. • There is lower portal and lower total hepatic flow and longer hepatic mean transit time and time-to-peak with gadoxetate disodium compared to gadobenate dimeglumine.

Diagnosis of Pre-HCC Disease by Hepatobiliary-Specific Contrast-Enhanced Magnetic Resonance Imaging: A Review.

We first proposed a new concept, pre-hepatocellular carcinoma (HCC) disease, to describe the precancerous condition of HCC, which has received scant attention from clinicians. Pre-HCC disease is defined as chronic liver injury concurrent with hepatic low- or high-grade dysplastic nodular lesions. Precise diagnosis of pre-HCC disease may prevent or arrest HCC and contribute to relieving the HCC burden worldwide, although noninvasive diagnosis is difficult and biopsy is generally required. Fortunately, recent advances and extensive applications of hepatobiliary-specific contrast-enhanced magnetic resonance imaging will facilitate the noninvasive identification and characterization of pre-HCC disease. This review briefly discusses the new concept of pre-HCC disease and offers an overview of the role of hepatobiliary-specific contrast-enhanced magnetic resonance imaging for the diagnosis of pre-HCC disease.

Comparison of gadolinium-enhanced and ferumoxytol-enhanced conventional and UTE-MRA for the depiction of the pulmonary vasculature.

PURPOSE: To evaluate the feasibility of ferumoxytol (FE)-enhanced UTE-MRA for depiction of the pulmonary vascular and nonvascular structures. METHODS: Twenty healthy volunteers underwent contrast-enhanced pulmonary MRA at 3 T during 2 visits, separated by at least 4 weeks. Visit 1: The MRA started with a conventional multiphase 3D T1 -weighted breath-held spoiled gradient-echo MRA before and after the injection of 0.1 mmol/kg gadobenate dimeglumine (GD). Subsequently, free-breathing GD-UTE-MRA was acquired as a series of 3 flip angles (FAs) (6°, 12°, 18°) to optimize T1 weighting. Visit 2: After the injection of 4 mg/kg FE, MRA was performed during the steady state, starting with a conventional 3D T1 -weighted breath-held spoiled gradient-echo MRA and followed by free-breathing FE-UTE-MRA, both at 4 different FAs (6°, 12°, 18°, 24°). The optimal FA for best T1 contrast was evaluated. Image quality at the optimal FA was compared between methods on a 4-point ordinal scale, using multiphase GD conventional pulmonary MRA (cMRA) as standard of reference. RESULTS: Flip angle in the range of 18°-24° resulted in best T1 contrast for FE cMRA and both UTE-MRA techniques (p > .05). At optimized FA, image quality of the vasculature was good/excellent with both FE-UTE-MRA and GD cMRA (98% versus 97%; p = .51). Both UTE techniques provided superior depiction of nonvascular structures compared with either GD-enhanced or FE-enhanced cMRA (p < .001). However, GD-UTE-MRA showed the lowest image quality of the angiogram due to low image contrast. CONCLUSION: Free-breathing UTE-MRA using FE is feasible for simultaneous assessment of the pulmonary vasculature and nonvascular structures. Patient studies should investigate the clinical utility of free-breathing UTE-MRA for assessment of pulmonary emboli.

Ascites relative enhancement during hepatobiliary phase after Gd-BOPTA administration: a new promising tool for characterising abdominal free fluid of unknown origin.

OBJECTIVES: To correlate the degree of ascites enhancement during hepatobiliary phase after gadobenate dimeglumine (Gd-BOPTA) administration with ascites aetiology. METHODS: IRB-approved retrospective study, need for informed consent was waived. We included 74 consecutive ascitic patients who underwent Gd-BOPTA-enhanced liver MRI including hepatobiliary phase (HBP) images between January 2014 and December 2017. Ascites appearance on unenhanced and HBP images was classified as hypo-, iso- or hyperintense in comparison to paraspinal muscles. Ascites signal intensity on unenhanced and HBP images was measured using round ROIs and was normalised to paraspinal muscles (NSI). Normalised relative enhancement (NRE) between native phase and HBP was calculated. The results were related to ascites aetiology using Wilcoxon and Mann-Whitney tests. RESULTS: On native images, ascites appeared hypointense in 95.9% of the cases and isointense in 4.1%, whereas on HBP images, it appeared hyperintense in 59.4% of the cases, isointense in 36.5% and hypointense in 4.1%. Mean ascites NSI was 0.52 on unenhanced images and 1.50 on HBP ones (p < 0.0001). Mean ascites NRE was 201 ± 133%. Ascites of non-malignant aetiology showed mean NRE of 210 ± 134%, whereas malignant ascites showed mean NRE of 92 ± 20% (p = 0.001). ROC analysis showed that a NRE < 112.5% correlates with malignant aetiology with 100% sensitivity and 83.4% specificity (LR = 5.667). NRE did not show any significant correlation with ascites thickness, eGFR and time interval between contrast administration and HBP acquisition (p > 0.05). CONCLUSIONS: Ascites NRE in HBP after Gd-BOPTA administration is significantly lower in patients with ascites secondary to peritoneal carcinomatosis than in patients with non-malignant ascites. KEY POINTS: • Ascites enhancement in the hepatobiliary phase after Gd-BOPTA administration may determine false positive findings when looking for biliary leaks. • Ascites enhancement in the hepatobiliary phase after Gd-BOPTA administration is lower in patients with peritoneal carcinomatosis than in patients with portal hypertension or congestive heart failure. • None of the patients with peritoneal carcinomatosis showed an ascites enhancement of more than 112% as compared with unenhanced images.

MRI for characterization of benign hepatocellular tumors on hepatobiliary phase: the added value of in-phase imaging and lesion-to-liver visual signal intensity ratio.

OBJECTIVES: To evaluate the lesion-to-liver visual signal intensity ratio (SIR) before and at the hepatobiliary phase MRI (HBP-MRI) after gadobenate dimeglumine (Gd-BOPTA) injection, using several T1-weighted images (T1-WI), for the characterization of benign hepatocellular lesions. METHODS: Patients with histologically proven focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), who underwent Gd-BOPTA-enhanced HBP-MRI from 2009 to 2017, were retrospectively identified. The lesion-to-liver SIR was visually assessed by two radiologists on HBP (post-HBP analysis) and compared with that of unenhanced sequences (pre/post-HBP analysis) on T1-WI in-phase (T1-IP), out-of-phase (T1-OP), and fat suppression (T1-FS). Lesions were classified as hyper-, iso-, or hypointense on post-HBP, and as decreasing, stable, or increasing SIR on pre/post-HBP analyses. The performance of the different T1-WI sequences for the diagnostic of FNH was evaluated on post-HBP analysis. RESULTS: Twenty-nine FNHs and 33 HCAs were analyzed. On post-HBP analysis, FNHs appeared hyper-/isointense in 89.7% of all T1-WI. HCAs appeared hypointense in 93.9%, 63.6%, and 69.7% of T1-IP, T1-OP, and T1-FS, respectively. FNHs exhibited an increasing SIR in 55.2-58.6%, a stable SIR in 44.8-58.6%, and a decreasing SIR in 0%, whereas HCAs exhibited a decreasing SIR in 66.7-93.9%, a stable SIR in 6.1-33.3%, and an increasing SIR in 0% (p < 0.0001). The specificity of T1-IP was significantly higher than that of T1-OP (p = 0.015) and T1-FS (p = 0.042). CONCLUSION: T1-IP is the most reliable sequence due to misleading tumor/liver signal ratio in the case of fatty liver when using T1-FS or T1-OP. The pre/post-HBP lesion-to-liver SIR is accurate to classify benign hepatocellular lesions and contributes to avoid biopsy. KEY POINTS: •The T1-weighted images in-phase should be systematically included in the HBP-MRI protocol, as it is the most reliable sequence especially in the case of fatty liver. •The comparison between lesion-to-liver signal intensity ratios on unenhanced and at the hepatobiliary phase sequences is useful to classify benign hepatocellular lesions in three categories without misclassification: FNH (increasing signal intensity ratio), HCA (decreasing signal intensity ration), and indeterminate lesions (stable signal intensity ratio).

Detection of liver metastases on gadobenate dimeglumine-enhanced MRI: systematic review, meta-analysis, and similarities with gadoxetate-enhanced MRI.

OBJECTIVES: To determine the sensitivity and positive predictive value (PPV) of gadobenate-enhanced MR imaging for the detection of liver metastases. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines. A comprehensive search (EMBASE, PubMed) was performed to identify relevant articles up to December 2017. Studies eligible for inclusion were performed using appropriate methodology with complete verification by means of histopathology, intraoperative observation and/or follow-up, and sufficient information to permit determination of true-positive (TP), false-negative (FN), and false-positive (FP) values. Sources of bias were assessed using the QUADAS-2 tool. An inverse variance-weighted random-effects model was used to obtain sensitivity and PPV estimates. Information was analyzed and presented using Cochran's Q statistic, funnel plots, and modified Deeks' analysis. RESULTS: Ten articles (256 patients, 562 metastases) were included. Sensitivity estimates for pre-contrast (unenhanced) imaging, gadobenate-enhanced dynamic imaging, and combined unenhanced, dynamic, and delayed hepatobiliary phase imaging for detecting liver metastases on a per-lesion basis were 77.8% (95% CI 71.4-84.3%, 7 assessments), 88.1% (95% CI, 84.0-92.2%, 13 assessments), and 95.1% (95% CI 93.1-97.1%, 15 assessments), respectively. The addition of hepatobiliary phase images significantly improved the detection of liver metastases. The overall PPV was 90.9% (95% CI 86.6-95.1%, 11 assessments). Deeks' funnel analysis revealed no association between sample size and sensitivity (ß = 0.02, p = 0.814) indicating no significant publication bias. CONCLUSIONS: Gadobenate-enhanced MR imaging has high sensitivity and PPV for the detection of liver metastases on a per-lesion basis. The sensitivity and PPV for detection is comparable to reported values for the pure liver-specific agent gadoxetate. KEY POINTS: • Gadobenate dimeglumine is a hepatobiliary MR contrast agent that permits acquisition of contrast-enhanced liver images during the immediate post-injection dynamic phase, like any extracellular agent, and in the delayed hepatobiliary phase, after specific uptake by the hepatocytes. • The hepatobiliary phase improves detection of liver metastases when compared either to pre-contrast unenhanced images alone or to pre-contrast + gadobenate-enhanced dynamic phase images. • The meta-analysis showed an overall sensitivity of 95.1% and PPV of 90.9% of gadobenate-enhanced MRI for the detection of metastases, when based on the evaluation of all available acquisitions.

Potential use of a diluted high-relaxivity gadolinium-based intra-articular contrast agent for magnetic resonance arthrography: an in-vitro study.

BACKGROUND: Magnetic resonance arthrography (MRA) requires intra-articular injection of gadolinium-based diluted paramagnetic contrast material. To our knowledge, gadobenate dimeglumine (Gd-BOPTA) has never been used for intra-articular applications. Our aim was to test in vitro different concentrations of Gd-BOPTA to be potentially used to perform MRA. METHODS: Gd-BOPTA was diluted in saline (NaCl 0.9%) to achieve different concentrations (4 mmol/l; 2 mmol/l; 1 mmol/l; 0.67 mmol/l; 0.5 mmol/l). Six sets of five sterile pipes were prepared with 5 ml of each solution, five sets added with 0.5 ml of fresh synovial fluid. Two separate pipes were prepared with 5 ml of gadopentetate dimeglumine (Gd-DTPA) at 2 mmol/l, one pipe added with 0.5 ml of synovial fluid. Pipes were imaged using a T1-weighted sequence at 1.5 T. For each pipe, signal intensity (SI) in arbitrary units (au) was measured. RESULTS: SI reproducibility range was 86-99%. Mean Gd-BOPTA SI in pipes containing synovial fluid increased from 1236 ± 8au (0.5 mmol/l) up to 1610 ± 44au (1 mmol/l) and down to 1405 ± 33au (4 mmol/l). Mean Gd-BOPTA SI in pipes without synovial fluid increased from 1184 ± 29au (0.5 mmol/l) up to 1530 ± 38au (1 mmol/l), and down to 1347 ± 39au (4 mmol/l). SI of pipes without synovial fluid was lower than that of pipes with synovial fluid for both Gd-BOPTA and Gd-DTPA (P ≤ 0.002). Regarding pipes with synovial fluid, mean Gd-DTPA SI at 2 mmol/l was 1246 ± 27au. Compared with Gd-BOPTA, SI was not different at 0.5 mmol/l (- 0.2%, P = 0.587) while it was higher (P < 0.001) at all other concentrations (range + 13.3%[4 mmol/l] - + 28.3%[1 mmol/l]). Regarding pipes without synovial fluid, mean Gd-DTPA SI at 2 mmol/l was 1275 ± 56au. Compared with Gd-BOPTA, SI was lower at 0.5 mmol/l (- 6.8%,P < 0.001), while it was higher (P < 0.001) at all other concentrations (range + 6.1%[4 mmol/l] - + 19.6% [1 mmol/l]). CONCLUSIONS: In vitro, Gd-BOPTA at 1 mmol/ had a + 28% SI increase in comparison to Gd-DTPA 2 mmol/l. SI similar to Gd-DTPA can be obtained using one fourth concentration of Gd-BOPTA.

Comparison of Visualization Rates of LI-RADS Version 2014 Major Features With IV Gadobenate Dimeglumine or Gadoxetate Disodium in Patients at Risk for Hepatocellular Carcinoma.

OBJECTIVE: The purpose of this study is to compare visualization rates of the major features covered by Liver Imaging Reporting and Data System (LI-RADS) version 2014 in patients at risk for hepatocellular carcinoma using either gadobenate dimeglumine or gadoxetate disodium IV contrast agent. MATERIALS AND METHODS: This retrospective study included liver MRI examinations performed with either gadobenate dimeglumine or gadoxetate disodium contrast enhancement. Using age, sex, underlying liver disease, and presence of cirrhosis, patients were placed into matched cohorts. All hepatic nodules 1 cm or larger (up to five per subject) were included, resulting in 63 subjects with 130 nodules (median nodule size, 1.9 cm) imaged with gadobenate and 64 subjects with 117 nodules (median nodule size, 2.0 cm) imaged with gadoxetate. Three radiologists reviewed the studies for LI-RADS major features independently. Bootstrap resampling with 10,000 repetitions was used to compare feature detection rates. RESULTS: Arterial phase hyperenhancement was seen in a similar number of nodules with gadobenate dimeglumine (mean, 91.5% [119/130]) and gadoxetate disodium (mean, 88.0% [103/117]) (p = 0.173). Dynamic phase washout was more commonly seen with gadobenate dimeglumine (mean, 60.2% [78.3/130]) than with gadoxetate disodium (mean, 45.3% [53/117]) (p = 0.006). The capsule feature was more often visualized with gadobenate dimeglumine (mean, 50.2% [65.3/130]) than with gadoxetate disodium (mean, 33.3% [39/117]) (p < 0.001). Interreader agreement for arterial phase enhancement and dynamic phase washout was almost perfect for both contrast agents (κ > 0.83). Agreement for the capsule feature was moderate for gadobenate dimeglumine (κ = 0.52) and substantial for gadoxetate disodium (κ = 0.67). CONCLUSION: The rates of visualization of arterial phase hyperenhancement are similar in studies performed with gadobenate dimeglumine and gadoxetate disodium, but dynamic phase washout and capsule appearance are more commonly visualized with gadobenate dimeglumine.

Efficacy comparison of multi-phase CT and hepatotropic contrast-enhanced MRI in the differential diagnosis of focal nodular hyperplasia: a prospective cohort study.

BACKGROUND: Different clinical behaviour influences the importance of differentiating focal nodular hyperplasia (FNH) from other focal liver lesions (FLLs). The aim of this study was to compare the efficacy of contrast-enhanced CT and MRI in the diagnosis of FNH. METHODS: 157 patients with equivocal FLLs detected in ultrasonography subsequently underwent multi-phase CT and MRI with the use of hepatotropic contrast agent (Gd-BOPTA) in a 1.5 T scanner. Examinations were evaluated by three independent readers. Diagnostic efficacy of different radiological signs of FNH in both CT and MRI was compared and AFROC analysis was performed. RESULTS: 4 hepatocellular adenomas, 95 hepatocellular carcinomas, 98 hemangiomas, 138 metastases and 45 FNHs were diagnosed. In both CT and MRI the radiological sign of the highest accuracy was the presence of the central scar within FNH (0.93 and 0.96 relatively). The sum of two radiological signs in MRI: homogeneous enhancement in hepatic arterial phase (HAP) and enhancing lesion in hepatobiliary phase (HBP) was characterized with high values of sensitivity (0.89), specificity (0.97), PPV (0.82), NPV (0.98) and accuracy (0.96). After inclusion of clinical data into analysis the best discriminating feature in MRI was the presence of enhancing lesion in HBP in patients without cirrhosis. In this regard, efficacy parameters increased to 1.00, 0.99, 0.94, 1.00 and 0.99 accordingly. The area under the curve in AFROC analysis of MRI performance was significantly larger than of CT (p = 0.0145). CONCLUSION: Gd-BOPTA-enhanced MRI is a more effective method in the differential diagnosis of FNH than multi-phase CT.

Non-clinical assessment of safety and gadolinium deposition after cumulative administration of gadobenate dimeglumine (MultiHance®) to neonatal and juvenile rats.

To determine the impact of single and cumulative doses of MultiHance on toxicity, pharmacokinetics, tissue gadolinium presence, behavior and neurological function in juvenile rats. Juvenile male and female rats received either physiological saline or MultiHance at 0.6, 1.25 or 2.5 mmol/kg bodyweight. Animals received either single or six consecutive MultiHance administrations and were sacrificed the day after the last administration or after a 60-day treatment-free period. Animals were assessed for behavior, cognitive function, grip strength, gait, pupillary reflex, and auditory reflex, as well as for physical development, sexual maturation and histopathology. Gadolinium presence in brain, femur, kidneys, liver and skin was determined using inductively coupled plasma-mass spectrometry (ICP-MS). No effects of MultiHance on behavior, cognitive function or any other parameter were noted, even for the highest administered cumulative dose (15 mmol/kg). Gadolinium presence was variable across tissues and decreased during the 60-day treatment-free period. The highest levels were noted in the femur and the lowest levels in the brain. Gadolinium presence in juvenile rat brain following single or repeated MultiHance administrations was minimal and non-impactful.

Crossover comparison of ferumoxytol and gadobenate dimeglumine for abdominal MR-angiography at 3.0 tesla: Effects of contrast bolus length and flip angle.

PURPOSE: Ferumoxytol (FE) has gained interest as an alternative to gadolinium-based contrast agents (GBCAs). The purpose of this study was to evaluate and optimize ferumoxytol dose and T1 weighting, in comparison to a conventional GBCA. MATERIALS AND METHODS: Twelve healthy volunteers (six women / six men, mean age 44.3 years) were recruited for this study. Scanning was performed on a clinical 3 Tesla (T) MRI system. Gadobenate dimeglumine (GD)-enhanced MRA was performed followed by FE-enhanced MRA 1 month later. Volunteers were randomly assigned to a diluted (n = 6) or undiluted (n = 6) dose of GD (0.1 mmol/kg), and to FE doses of 4 mg/kg (n = 6) or 2 mg/kg (n = 6). First pass and steady-state MRA were performed for GD- and FE-enhanced MRA. Flip-angle optimization was performed after FE administration. Quantitative analysis included relative contrast-to-noise ratio (relCNR) measurements for all acquisitions. First pass GD- and FE-enhanced MRA images were evaluated qualitatively. RESULTS: RelCNR was significantly higher with undiluted GD (31.8, 95% confidence interval [CI], 27.7-35.9) compared with diluted GD (16.2; 95% CI, 12.2-20.3; P = 0.001) and both 4 mg/kg FE (12.5; 95% CI, 8.5-16.4; P < 0.001) and 2 mg/kg FE (9.1; 95% CI, 5.1-13.2; P < 0.001) during first pass. Relative CNR did not decrease with FE 5 min postinjection compared with GD. Flip-angle analysis revealed relative CNR-peaks at 30° for FE 4 mg/kg and at 20° for FE 2 mg/kg. Diluted GD (P = 0.013) and FE 4 mg/kg (P = 0.01) revealed significantly higher image quality scores compared with undiluted GD during first pass. CONCLUSION: This study shows an equivalent image quality of FE and GD for first pass MRA even though GD showed significantly higher relative CNR. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1617-1626.

The value of Gd-BOPTA- enhanced MRIs and DWI in the diagnosis of intrahepatic mass-forming cholangiocarcinoma.

The aim of this study is to explore the value of unenhanced magnetic resonance imaging (MRI), gadobenate dimeglumine injection (Gd-BOPTA)-enhanced MRI and diffusion-weighted imaging (DWI) in the diagnosis of intrahepatic mass-forming cholangiocarcinoma (IMCC). Totally 59 IMCC patients who underwent Gd-BOPTA-enhanced MRIs were recruited. The time-signal intensity curves and lesion periphery enhancement rates of the IMCC and liver parenchyma was drawn using apparent diffusion coefficient (ADC) values. The Gd-BOPTA-enhanced MRI showed that the peripheries of 30 lesions in the arterial phase exhibited irregular ring enhancement. However, lesions in the portal and delayed phases (which were gradually filled with a contrast agent), presented a patchy or latticed enhancement. Twenty-two lesions in the arterial and delayed phases exhibited uneven mild/moderate patchy enhancements with a progressive and centripetal lesion. Five lesions emerged from the arterial phase without any significant enhancement and had only gradual enhancement during the delayed phase. The remaining 2 lesions had a decreased mild enhancement, presented comparatively high signals and the lesion center had visible small spotted low signals. The DWI signals displayed a slightly high or high unevenness. Some lesion peripheries had a high signal but lesion centers displayed a relatively low or slightly low signal and irregular patches. There were significant differences between the ADC values of the lesion edge, lesion center and liver parenchyma. The IMCC detection rates of the Gd-BOPTA-enhanced MRI and DWI were higher than those of the unenhanced MRI. Our study demonstrated that both the Gd-BOPTA-enhanced MRI and DWI had higher accuracies rates than an unenhanced MRI. Furthermore, the hepatobiliary phase of IMCC plays an important role in the diagnosis and identification of IMCC constituents.

A Pictorial Review of Hepatobiliary Magnetic Resonance Imaging With Hepatocyte-Specific Contrast Agents: Uses, Findings, and Pitfalls of Gadoxetate Disodium and Gadobenate Dimeglumine.

Magnetic resonance imaging (MRI) has a well-established role as a highly specific and accurate modality for characterizing benign and malignant focal liver lesions. In particular, contrast-enhanced MRI using hepatocyte-specific contrast agents (HSCAs) improves lesion detection and characterization compared to other imaging modalities and MRI techniques. In this pictorial review, the mechanism of action of gadolinium-based MRI contrast agents, with a focus on HSCAs, is described. The clinical indications, protocols, and emerging uses of the 2 commercially available combined contrast agents available in the United States, gadoxetate disodium and gadobenate dimeglumine, are discussed. The MRI features of these agents are compared with examples of focal hepatic masses, many of which have been obtained within the same patient therefore allowing direct lesion comparison. Finally, the pitfalls in the use of combined contrast agents in liver MRI are highlighted.

Effect of increasing the flip angle during the hepatocyte phase of gadobenate dimeglumine-enhanced 1.5T MRI in cirrhotic patients with hepatocellular carcinoma.

PURPOSE: To evaluate the effects of increasing the flip angle during the hepatocyte phase of gadobenate dimeglumine-enhanced magnetic resonance imaging (MRI) in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Sixty-three patients with liver cirrhosis underwent gadobenate dimeglumine-enhanced 1.5T MRI with 90-minute delayed hepatocyte phase with flip angles of 10°, 20°, 30°, consecutively. Relative enhancement and signal-to-noise ratio (SNR) of liver parenchyma at hepatocyte phase according to flip angle were calculated. The liver-to-lesion (low signal intensity HCCs, n = 63; ≥1 cm) and contrast-to-noise ratio (CNR) at the hepatocyte phase according to flip angle were calculated. Two radiologists independently assessed the presence of HCCs using a 5-point scale, and detection sensitivity of HCCs was calculated according to flip angle. RESULTS: The relative enhancement of hepatic parenchyma differed significantly according to flip angle (10°, mean relative enhancement = 0.69 ± 0.46; 20°, mean relative enhancement = 0.63 ± 0.47; 30°, mean relative enhancement = 0.49 ± 0.45; P = 0.043). The SNR of hepatic parenchyma was significantly different according to flip angle (10°, mean SNR = 26.2 ± 5.6; 20°, mean SNR = 25.3 ± 5.7; 30°, mean SNR = 22.8 ± 6.1; P = 0.004). The CNR of lesion was not significantly different according to flip angle (10°, mean CNR = 7.5 ± 6.6; 20°, mean CNR = 10.2 ± 6.9; 30°, mean CNR = 10.1 ± 7.1; P = 0.051). The sensitivities with 10° and 20° for HCCs were significantly higher than those with 30° for one reader (P < 0.05). CONCLUSION: In patients with cirrhosis, hepatocyte phase gadobenate dimeglumine-enhanced 1.5T MRI with 20° flip angle should be recommended rather than 10° and 30° flip angle.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus following gadobenate dimeglumine in patients with and without previous multiple administrations of gadodiamide.

OBJECTIVES: To evaluate the impact of previous administration of gadodiamide and neural tissue gadolinium deposition in patients who received gadobenate dimeglumine. METHODS: Our population included 62 patients who underwent at least three administrations of gadobenate dimeglumine, plus an additional contrast-enhanced last MRI for reference, divided into two groups: group 1, patients who in addition to gadobenate dimeglumine administrations had prior exposure to multiple doses of gadodiamide; group 2, patients without previous exposure to other gadolinium-based contrast agent (GBCAs). Quantitative analysis was performed on the first and last gadobenate dimeglumine MRIs in both groups. Dentate nucleus-to-middle cerebellar peduncle signal intensity ratios (DN/MCP) and relative change (RC) in signal over time were calculated and compared between groups using generalized additive model. RESULTS: Group 1 showed significant increase in baseline and follow-up DN/MCP compared to group 2 (p < 0.0001). The RC DN/MCP showed a non-statistically significant trend towards an increase in patients who underwent previous gadodiamide (p = 0.0735). CONCLUSION: There is increased T1 signal change over time in patients who underwent gadobenate dimeglumine and had received prior gadodiamide compared to those without known exposure to previous gadodiamide. A potentiating effect from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur. KEY POINTS: • Neural gadolinium deposition is associated with multiple administrations of less stable GBCAs. • Less stable GBCA effect on subsequent more stable GBCA administrations is undetermined. • Significant increase of DN/MCP was seen in patients with previous gadodiamide exposure. • RC DN/MCP showed a non-significant increase in patients who received previous gadodiamide. • Potentiating effects from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur.