Current and Advanced Applications of Gadoxetic Acid-enhanced MRI in Hepatobiliary Disorders.

Gadoxetic acid is an MRI contrast agent that has specific applications in the study of hepatobiliary disease. After being distributed in the vascular and extravascular spaces during the dynamic phase, gadoxetic acid is progressively taken up by hepatocytes and excreted to the bile ducts during the hepatobiliary phase. The information derived from the enhancement characteristics during dynamic and hepatobiliary phases is particularly relevant in the detection and characterization of focal liver lesions and in the evaluation of the structure and function of the liver and biliary system. The use of new MRI sequences and advanced imaging techniques (eg, relaxometry, multiparametric imaging, and analysis of heterogeneity), the introduction of artificial intelligence, and the development of biomarkers and radiomic and radiogenomic tools based on gadoxetic acid-enhanced MRI findings will play an important role in the future in assessing liver function, chronic liver disease, and focal liver lesions; in studying biliary pathologic conditions; and in predicting treatment responses and prognosis. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study.

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

How to Perform Curative Laparoscopic Hepatectomy for Intraoperatively Unidentified Hepatocellular Carcinoma.

BACKGROUND/AIM: Detection of hepatocellular carcinoma using intraoperative ultrasonography (IOUS) is indispensable for successful laparoscopic hepatectomy (LH). This study was performed to evaluate patients with intraoperatively unidentified tumours undergoing LH. PATIENTS AND METHODS: Seven patients who underwent LH for hepatocellular carcinoma and whose tumours were not detected using IOUS were included in this study. Clinical features, preoperative imaging, intraoperative imaging, surgical procedures, and pathological findings were evaluated. RESULTS: Using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, all the tumours were enhanced in the arterial phase and rapidly washed out, becoming hypointense to the remainder of the liver. All tumours except one were <2 cm in size. Severe liver fibrosis was observed in all cases. Tumours that were invisible on preoperative ultrasonography also could not be detected using IOUS or indocyanine green fluorescence imaging. Five patients underwent hepatectomy based on anatomical landmarks and achieved curative resection, whereas curative resection failed in two patients. CONCLUSION: When tumours cannot be identified by IOUS, LH based on anatomical landmarks should be preferred. Importantly, invisible tumours on preoperative ultrasonography may not be identified intraoperatively during LH.

Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats.

Physiologically based pharmacokinetic (PBPK) models are increasingly used in drug development to simulate changes in both systemic and tissue exposures that arise as a result of changes in enzyme and/or transporter activity. Verification of these model-based simulations of tissue exposure is challenging in the case of transporter-mediated drug-drug interactions (tDDI), in particular as these may lead to differential effects on substrate exposure in plasma and tissues/organs of interest. Gadoxetate, a promising magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 (OATP1B1) and multidrug resistance-associated protein 2 (MRP2). In this study, we developed a gadoxetate PBPK model and explored the use of liver-imaging data to achieve and refine in vitro-in vivo extrapolation (IVIVE) of gadoxetate hepatic transporter kinetic data. In addition, PBPK modeling was used to investigate gadoxetate hepatic tDDI with rifampicin i.v. 10 mg/kg. In vivo dynamic contrast-enhanced (DCE) MRI data of gadoxetate in rat blood, spleen, and liver were used in this analysis. Gadoxetate in vitro uptake kinetic data were generated in plated rat hepatocytes. Mean (%CV) in vitro hepatocyte uptake unbound Michaelis-Menten constant (Km,u) of gadoxetate was 106 µM (17%) (n = 4 rats), and active saturable uptake accounted for 94% of total uptake into hepatocytes. PBPK-IVIVE of these data (bottom-up approach) captured reasonably systemic exposure, but underestimated the in vivo gadoxetate DCE-MRI profiles and elimination from the liver. Therefore, in vivo rat DCE-MRI liver data were subsequently used to refine gadoxetate transporter kinetic parameters in the PBPK model (top-down approach). Active uptake into the hepatocytes refined by the liver-imaging data was one order of magnitude higher than the one predicted by the IVIVE approach. Finally, the PBPK model was fitted to the gadoxetate DCE-MRI data (blood, spleen, and liver) obtained with and without coadministered rifampicin. Rifampicin was estimated to inhibit active uptake transport of gadoxetate into the liver by 96%. The current analysis highlighted the importance of gadoxetate liver data for PBPK model refinement, which was not feasible when using the blood data alone, as is common in PBPK modeling applications. The results of our study demonstrate the utility of organ-imaging data in evaluating and refining PBPK transporter IVIVE to support the subsequent model use for quantitative evaluation of hepatic tDDI.

The value of the signal intensity of peritumoral tissue on Gd-EOB-DTPA dynamic enhanced MRI in assessment of microvascular invasion and pathological grade of hepatocellular carcinoma.

ABSTRACT: The aim of the study was to assess the potential role of preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) dynamic enhanced MR imaging for diagnosing microvascular invasion (MVI) and pathological grade of hepatocellular carcinoma (HCC).A total of 113 consecutive HCC patients confirmed by histopathology underwent preoperative Gd-EOB-DTPA dynamic enhanced MRI were included. Signal intensity (SI) of peritumoral, normal liver tissue and tumor parenchyma during arterial phase and hepatobiliary phase (HBP) were analyzed. The receiver operating characteristic (ROC) curves were performed to assess the potential diagnostic capability for MVI and pathological grade of HCC. Kaplan-Meier method was performed to estimate the recurrence-free survival rate and compared using the log rank test.SI ratio of peritumoral tissue to normal liver in arterial phase (SIAp/Al) was independently associated with MVI [odds ratio (OR) = 3.115, 95% confidence interval (CI): 1.867-5.198] and pathological grades (OR = 1.437, 95% CI: 1.042-1.981). The area under the curve (AUC) of SIAp/Al was equivalent to the SI of tumor parenchyma on arterial phase (SIAt) in distinguishing low and high pathological grades. However, the AUC of SIAp/Al (0.851) was larger than peritumoral hypointensity on HBP (0.668) for distinguishing MVI. The recurrence-free survival rate of HCC patients with SIAp/Al<1.1 was higher than HCC with SIAp/Al≥1.1(P = .025).The SIAp/Al in preoperative Gd-EOB-DTPA dynamic enhanced MR imaging is a potential diagnosis marker for MVI and pathological grade of HCC noninvasively. The higher SIAp/Al may predict the poor prognosis of HCC after surgery.

Utility of Radial Scanning for the Identification of Arterial Hypervascularity of Hepatocellular Carcinoma on Gadoxetic Acid-Enhanced Magnetic Resonance Images.

OBJECTIVES: This study aimed to compare the accuracy of assessing the arterial hypervascularity of hepatocellular carcinoma (HCC) on dynamic computed tomography (CT) scans and gadoxetic acid (EOB)-enhanced magnetic resonance imaging (MRI) scans performed with radial sampling. METHODS: We studied the images of 40 patients with hypervascular HCC. A radiologist recorded the standard deviation of the attenuation (or the signal intensity [SI]) in subcutaneous fat tissue as the image noise (N) and calculated the contrast-to-noise ratio (CNR) as follows: (CNR) = (n-ROIT - n-ROIL)/N, where n-ROIT is the mean attenuation (or SI) of the tumor divided by the mean attenuation (or SI) of the aorta and n-ROIL is the mean attenuation (or SI) of the liver parenchyma divided by the mean attenuation (or SI) of the aorta. RESULTS: The CNR was significantly higher on EOB-enhanced MRI than on dynamic CT scans. CONCLUSIONS: For the assessment of HCC vascularity, EOB-enhanced MRI scans acquired with radial sampling were more accurate than dynamic CT images.

Gadolinium-based contrast agents: in vitro paraoxonase 1 inhibition, in silico studies.

Medications show their biological effects by interaction with enzymes, which have been known to play an essential role in the pathogenesis of many diseases. Inhibition or induction of drug metabolizing enzymes has an essential place in the drug design for many kinds of diseases including cardiovascular, neurological, metabolic, and cancer. The main goal of the current study is to contribute to this growing drug design field by observing PON1-drug interactions. In recent years, the safety of gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI) has discussed. In the present study, paraoxonase 1 (PON1) enzyme was purified from human serum by simple chromatographic methods with 4095.24 EU mg-1 protein specific activity. The inhibitory activities of gadoteric acid, gadopentetic acid, gadoxetate disodium, and gadodiamide were investigated on PON1 activity of the enzyme. IC50 values were found in the range of 51.28 ± 0.14 to 285.80 ± 0.96 mM. Ki constants were found as 67.95 ± 0.60 mM, 104.97 ± 0.96 mM, 202.33 ± 1.75 mM, and 299.43 ± 2.64 mM for gadoteric acid, gadopentetic acid, gadoxetate disodium, and gadodiamide, respectively. While the inhibition types are determined as competitive of gadoxetate disodium and gadodiamide by the Lineweaver-Burk curves, it was noncompetitive for other compounds. In addition, the molecular docking analyses of gadoxetate disodium and gadodiamide were carried out to understand the binding interactions on the active site of the PON1 enzyme. The structure-activity relationship (SAR) of the drugs was established on the basis of different substituents and their positions in the compounds.

Optimization of Contrast Agent Dosage on Contrast-Enhanced T2 Fluid-Attenuated Inversion Recovery: An In Vitro and In Vivo Study.

OBJECTIVE: This study aimed to ascertain the minimum gadolinium dosage on contrast-enhanced (CE) T2 fluid-attenuated inversion recovery (FLAIR) at appropriate imaging time. METHODS: Different dosages of gadodiamide were imaged with a 3.0-T magnetic resonance scanner for T2-FLAIR and T1WI. Twenty glioma-induced rat models were randomly assigned into 4 groups (1/2, 1/4, 1/6, 1/8 of routine dosage) and imaged for T2-FLAIR and T1WI preinjection and postinjection of gadodiamide. Contrast-enhanced T2-FLAIR was acquired for 8 repetitions postinjection. Enhancement effects were assessed by calculating contrast-noise ratio and contrast ratio using Kruskal-Wallis and Mann-Whitney rank sum test. RESULTS: The in vitro experiment showed that gadodiamide at 1/4 of the T1WI dosage presented the best contrast on CE-T2-FLAIR. For in vivo study, the best enhancement effect on CE-T2-FLAIR was achieved at 1/2 of the routine dosage at 8 to 12 minutes of delayed scanning. Compared with CE-T1WI at routine dosage, CE-T2-FLAIR at 1/2 gadodiamide dosage presented similar enhancement effects with no statistical difference (P = 0.244 and 0.090 for contrast-noise ratio and contrast ratio, respectively). CONCLUSIONS: Contrast-enhanced T2-FLAIR imaging with half of T1WI routine gadodiamide dosage can produce similar enhancement effects to CE-T1WI when characterizing brain gliomas. The cut-down of contrast agent dosage may help reduce gadolinium accumulation in certain tissues.

Incremental prognostic value of coronary flow reserve determined by phase-contrast cine cardiovascular magnetic resonance of the coronary sinus in patients with diabetes mellitus.

BACKGROUND: Although non-invasive assessment of coronary flow reserve (CFR) by cardiovascular magnetic resonance (CMR) provides prognostic information for patients with diabetes mellitus (DM), the incremental prognostic value of CMR-derived CFR remains unclear. PURPOSE: To evaluate the incremental prognostic value of CMR-derived CFR for patients with DM who underwent stress CMR imaging. MATERIALS AND METHODS: A total of 309 patients with type 2 DM [69 ± 9 years; 244 (78%) male] assessed between 2009 and 2019 were retrospectively reviewed. Coronary sinus blood flow (CSBF) was measured using phase contrast (PC) cine CMR. CFR was calculated as the CSBF during adenosine triphosphate infusion divided by that at rest. Major adverse cardiac events (MACE) were defined as death, acute coronary syndrome, hospitalization due to heart failure exacerbation, or sustained ventricular tachycardia. The incremental prognostic value of CFR over clinical and CMR variables was assessed by calculating the C-index and net reclassification improvement (NRI). RESULTS: During a median follow-up of 3.8 years, 42 patients (14%) experienced MACE. The annualized event rate was significantly higher among patients with CFR < 2.0, regardless of the presence of late gadolinium enhancement (LGE) (1.4% vs. 9.8%, p = 0.011 in the LGE (-) group; 1.8% vs. 16.9%, p < 0.001 in the LGE (+) group). In addition, this trend was maintained in the subgroups stratified by presence or absence of ischemia (0.3% vs. 6.7%, p = 0.007 in the ischemia (-) group; 3.9% vs. 17.1%, p = 0.001 in the ischemia (+) group). Adding CFR to the risk model (age + gender + left ventricular ejection fraction + %LGE + %ischemia) resulted in a significant increase of the C-index from 0.838 to 0.870 (p = 0.038) and an NRI of 0.201 (0.004-0.368, p = 0.012). CONCLUSION: PC cine CMR-derived CFR of the coronary sinus may be useful as a prognostic marker for DM patients, incremental to common clinical and CMR parameters. Due to the high prevalence of coronary microvascular dysfunction, the addition of CFR to conventional vasodilator stress CMR imaging may improve risk stratification for patients with DM.

No Cases of Nephrogenic Systemic Fibrosis after Administration of Gadoxetic Acid.

Background Gadoxetic acid (GA) has distinctive pharmacokinetic properties with important applications in hepatobiliary imaging. However, there are limited data evaluating the safety of GA administration in patients with impaired kidney function and the incidence of nephrogenic systemic fibrosis (NSF). Purpose To evaluate safety of GA regarding risk of NSF in patients with impaired kidney function. Materials and Methods This retrospective study identified all GA-enhanced MRI (hereafter, GA MRI) examinations performed between July 2008 and December 2019 through a search of the electronic medical record. Serum creatinine values within 180 days or less of each GA MRI examination were retrieved and estimated glomerular filtration rate (eGFR) was calculated. The eGFR value nearest to each MRI examination was used. A separate search in the electronic medical record was also performed to identify patients with NSF. Dermatologists, nephrologists, and nephrologists at our institution were surveyed for any cases of NSF. In patients with NSF, all MRI examinations performed and contrast agents administered to these patients were recorded. Results Overall, 7820 GA MRI examinations were identified, performed in 5351 patients (3022 women and 2329 men). These included 299 examinations (242 patients) with eGFR of 30-44 mL/min/1.73 m2 and 183 examinations (157 patients) with eGFR less than 30 mL/min/1.73 m2. There were 109 examinations (in 94 patients) with eGFR of 15-29 mL/min/1.73 m2, 40 examinations (in 39 patients) with eGFR less than 15 mL/min/1.73 m2, and 34 examinations in 27 patients undergoing hemodialysis. Seventeen patients with eGFR less than 30 mL/min/1.73 m2 or undergoing dialysis underwent GA MRI two or more times. Eighteen patients with biopsy-confirmed NSF were identified, none of whom were exposed to GA. The mean follow-up period for GA MRI examinations performed in patients with severe kidney impairment was 4.2 years (range, 0.2-11.3 years). Conclusion Gadoxetic acid may be safe with respect to nephrogenic systemic fibrosis in this patient population, although further studies are needed to confirm this. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Davenport and Shankar in this issue.

Anterior pituitary gland T1 signal intensity is influenced by time delay after injection of gadodiamide.

To test the hypothesis of washout from the anterior pituitary (AP) gland after serial injections of gadodiamide. We included 59 patients with history of at least 5 injections of gadodiamide. Values of mean signal intensity of the AP and of the central pons were measured on unenhanced sagittal T1-weighted images. AP-to-pons signal intensity ratios were calculated dividing the values of the AP by those of the pons. The measurements were performed using MR images acquired at four different time points including baseline (prior to any gadodiamide injection), minimum post-injection time delay, maximum post-injection time delay, and last available MR scans. Normalized ratios (i.e. ratios divided total volume of injected gadodiamide) were also calculated. To assess the difference between ratios, non-parametric Wilcoxon signed-rank test was applied. The correlations were tested with non-parametric Spearman correlation coefficient. A p-value < 0.05 was considered as statistically significant. A statistically significant increase of AP signal intensity was found by comparing the baseline scans with both the minimum time delay (p = 0.003) and maximum time delay scans (p = 0.005). We found significant higher normalized ratios for minimum post-injection time delay with respect to maximum post-injection time delay (p < 0.001). The normalized ratios demonstrated a statistically significant negative correlation with the post-injection time delay (r = - 0.31; p = 0.006). The findings of this study suggest that washout phenomena of retained/deposited gadolinium from the AP are influenced by the total injected volume and post-injection time delay.

Texture analysis of MR images to identify the differentiated degree in hepatocellular carcinoma: a retrospective study.

BACKGROUND: To explore the clinical value of texture analysis of MR images (multiphase Gd-EOB-DTPA-enhanced MRI and T2 weighted imaging (T2WI) to identify the differentiated degree of hepatocellular carcinoma (HCC). METHOD: One hundred four participants were enrolled in this retrospective study. Each participant performed preoperative Gd-EOB-DTPA-enhanced MR scanning. Texture features were analyzed by MaZda, and B11 program was used for data analysis and classification. The diagnosis efficiencies of texture features and conventional imaging features in identifying the differentiated degree of HCC were assessed by receiver operating characteristic analysis. The relationship between texture features and differentiated degree of HCC was evaluated by Spearman's correlation coefficient. RESULTS: The grey-level co-occurrence matrix -based texture features were most frequently extracted and the nonlinear discriminant analysis was excellent with the misclassification rate ranging from 3.33 to 14.93%. The area under the curve (AUC) of the combined texture features between poorly- and well-differentiated HCC, poorly- and moderately-differentiated HCC, moderately- and well-differentiated HCC was 0.812, 0.879 and 0.808 respectively, while the AUC of tumor size was 0.649, 0.660 and 0.517 respectively. The tumor size was significantly different between poorly- and moderately-HCC (p = 0.014). The COMBINE AUC values were not increased with tumor size combined. CONCLUSIONS: Texture analysis of Gd-EOB-DTPA-enhanced MRI and T2WI was valuable and might be a promising method in identifying the differentiated degree of HCC. The poorly-differentiated HCC was more heterogeneous than well- and moderately-differentiated HCC.

Hepatic uptake index in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine penta acetic acid-enhanced magnetic resonance imaging estimates functional liver reserve and predicts post-hepatectomy liver failure.

BACKGROUND: Recent evidence suggests that gadolinium ethoxybenzyl diethylenetriamine penta acetic acid-enhanced (Gd-EOB-DTPA) magnetic resonance imaging may be used to evaluate liver function. The aim of this study was to assess whether the signal intensity of Gd-EOB-DTPA magnetic resonance imaging may be used to predict functional liver reserve and posthepatectomy liver failure in patients undergoing hepatectomy for liver tumors. METHODS: This is an observational retrospective study on 137 preoperative Gd-EOB-DTPA magnetic resonance imaging of patients undergoing hepatectomy between 2015 and 2018. Mean signal intensity of liver (L20) and spleen (S20) were measured on T1-weighted single-breath-hold 3-dimensional fat-saturated gradient echo sequences acquired 20 minutes after Gd-EOB-DTPA administration. The hepatocellular uptake index of liver volume (VL) was calculated with the formula VL([L20/S20] - 1) and was tested with several score systems for liver diseases and to the occurrence of post-hepatectomy liver failure. RESULTS: Patients with diseased liver had significantly lower values of hepatic uptake index in comparison with those with normal function. This was found for a Model for End-Stage Liver Disease score ≤9 versus >9 (P = .04), combination of bilirubin and cholinesterases levels score ≤2 versus >2 (P = .02), albumin to bilirubin grades (P = .03), and Humanitas score ≤6 versus >6 (P = .03). Twenty-two patients (16%) developed posthepatectomy liver failure, and 2 (1.4%) died within 90 days. The hepatocellular uptake index was significantly lower in those patients with posthepatectomy liver failure (P < .01). Receiver operating characteristics curve analysis revealed valuable hepatocellular uptake index ability in predicting post-hepatectomy liver failure (area under the curve = 0.84; 95% confidence interval, 0.71-0.92; P < .01), with a cutoff value of 574.33 (98% sensitivity; 83% specificity). CONCLUSION: The hepatocellular uptake index hepatocellular uptake index measured on preoperative Gd-EOB-DTPA magnetic resonance imaging identifies patients with diseased liver and predicts posthepatectomy liver failure. This index could be used to discern those patients at higher risk of complications after hepatectomy.

Hepatocyte-specific contrast-enhanced MRI findings of focal nodular hyperplasia-like nodules in the liver following chemotherapy in pediatric cancer patients.

PURPOSE: We aimed to assess the MRI findings and follow-up of multiple focal nodular hyperplasia (FNH)- like lesions in pediatric cancer patients diagnosed by imaging findings. METHODS: We retrospectively analyzed clinical data and MRI examinations of 16 pediatric patients, who had been scanned using gadoxetate disodium (n=13) and gadobenate dimeglumine (n=3). Hepatic nodules were reviewed according to their number, size, contour, T1- and T2-weighted signal intensities, arterial, portal, delayed and hepatobiliary phase enhancement patterns. Follow-up images were evaluated for nodule size, number, and appearance. RESULTS: All 16 patients received chemotherapy in due course. Time interval between the initial diagnosis of cancer and detection of the hepatic nodule was 2-14 years. Three patients had a single lesion, 13 patients had multiple nodules. The median size of the largest nodules was 19.5 mm (range, 8-41 mm). Among 16 patients that received hepatocyte-specific agents, FNH-like nodules appeared hyperintense in 11 and isointense in 5 on the hepatobiliary phase. During follow-up, increased number and size of the nodules were seen in 4 patients. The nodules showed growth between 6-15 mm. CONCLUSION: Liver MRI using hepatocyte-specific agents is a significant imaging method for the diagnosis of FNH-like lesions, which can occur in a variety of diseases. Lesions can increase in size and number in pediatric patients.

Value of T1 mapping on gadoxetic acid-enhanced MRI for microvascular invasion of hepatocellular carcinoma: a retrospective study.

BACKGROUND: To evaluate the utility of non-invasive parameters derived from T1 mapping and diffusion-weighted imaging (DWI) on gadoxetic acid-enhanced MRI for predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). METHODS: A total of 94 patients with single HCC undergoing partial hepatectomy was analyzed in this retrospective study. Preoperative T1 mapping and DWI on gadoxetic acid-enhanced MRI was performed. The parameters including precontrast, postcontrast and reduction rate of T1 relaxation time and apparent diffusion coefficient (ADC) values were measured for differentiating MVI-positive HCCs (n = 38) from MVI-negative HCCs (n = 56). The receiver operating characteristic curve (ROC) was analyzed to compare the diagnostic performance of the calculated parameters. RESULTS: MVI-positive HCCs demonstrated a significantly lower reduction rate of T1 relaxation time than that of MVI-negative HCCs (39.4% vs 49.9, P < 0.001). The areas under receiver operating characteristic curve (AUC) were 0.587, 0.728, 0.824, 0,690 and 0.862 for the precontrast, postcontrast, reduction rate of T1 relaxation time, ADC and the combination of reduction rate and ADC, respectively. The cut-off value of the reduction rate and ADC calculated through maximal Youden index in ROC analyses was 44.9% and 1553.5 s/mm2. To achieve a better diagnostic performance, the criteria of combining the reduction rate lower than 44.9% and the ADC value lower than 1553.5 s/mm2 was proposed with a high specificity of 91.8% and accuracy of 80.9%. CONCLUSIONS: The proposed criteria of combining the reduction rate of T1 relaxation time lower than 44.9% and the ADC value lower than 1553.5 s/mm2 on gadoxetic acid-enhanced MRI holds promise for evaluating MVI status of HCC.

Radiomics model based on preoperative gadoxetic acid-enhanced MRI for predicting liver failure.

BACKGROUND: Postoperative liver failure is the most severe complication in cirrhotic patients with hepatocellular carcinoma (HCC) after major hepatectomy. Current available clinical indexes predicting postoperative residual liver function are not sufficiently accurate. AIM: To determine a radiomics model based on preoperative gadoxetic acid-enhanced magnetic resonance imaging for predicting liver failure in cirrhotic patients with HCC after major hepatectomy. METHODS: For this retrospective study, a radiomics-based model was developed based on preoperative hepatobiliary phase gadoxetic acid-enhanced magnetic resonance images in 101 patients with HCC between June 2012 and June 2018. Sixty-one radiomic features were extracted from hepatobiliary phase images and selected by the least absolute shrinkage and selection operator method to construct a radiomics signature. A clinical prediction model, and radiomics-based model incorporating significant clinical indexes and radiomics signature were built using multivariable logistic regression analysis. The integrated radiomics-based model was presented as a radiomics nomogram. The performances of clinical prediction model, radiomics signature, and radiomics-based model for predicting post-operative liver failure were determined using receiver operating characteristics curve, calibration curve, and decision curve analyses. RESULTS: Five radiomics features from hepatobiliary phase images were selected to construct the radiomics signature. The clinical prediction model, radiomics signature, and radiomics-based model incorporating indocyanine green clearance rate at 15 min and radiomics signature showed favorable performance for predicting postoperative liver failure (area under the curve: 0.809-0.894). The radiomics-based model achieved the highest performance for predicting liver failure (area under the curve: 0.894; 95%CI: 0.823-0.964). The integrated discrimination improvement analysis showed a significant improvement in the accuracy of liver failure prediction when radiomics signature was added to the clinical prediction model (integrated discrimination improvement = 0.117, P = 0.002). The calibration curve and an insignificant Hosmer-Lemeshow test statistic (P = 0.841) demonstrated good calibration of the radiomics-based model. The decision curve analysis showed that patients would benefit more from a radiomics-based prediction model than from a clinical prediction model and radiomics signature alone. CONCLUSION: A radiomics-based model of preoperative gadoxetic acid-enhanced MRI can be used to predict liver failure in cirrhotic patients with HCC after major hepatectomy.

Targetoid hepatic observations on gadoxetic acid-enhanced MRI using LI-RADS version 2018: emphasis on hepatocellular carcinomas assigned to the LR-M category.

AIM: To determine useful imaging features for differentiating hepatocellular carcinoma (HCC) categorised as LR-M from non-HCC malignancies in using the Liver Imaging-Reporting and Data System (LI-RADS) version 2018 on gadoxetic acid-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Patients at high-risk for HCC with surgically confirmed HCCs (n=131) and non-HCC malignancies (n=90) and who had undergone gadoxetic acid-enhanced MRI were included. LI-RADS categories were assigned to identify hepatic observations defined as LR-M by two radiologists. Major and ancillary imaging features of hepatic observation with targetoid appearance including intratumoural septa were compared between HCCs and non-HCC malignancies. A classification tree analysis (CTA) was applied to differentiate high-risk HCCs from non-HCC malignancies in the LR-M category. RESULTS: A total of 36 HCCs (27.5%) and 70 non-HCC malignancies (77.8%) were assigned as LR-M. An enhancing capsule (p=0.0293), blood products in the mass (p=0.0393), non-targetoid restriction (p=0.018), and a septum (p=0.0053) were significantly predictive of HCC. On CTA, the presence of a septum was an initial predictor for a high probability of HCC followed by non-targetoid restriction. The CTA model has a sensitivity of 63.9%, specificity of 90%, and accuracy of 81.1% for differentiating HCC assigned LR-M from non-HCC malignancy. CONCLUSION: A considerable proportion of HCCs could have been categorised as LR-M as they had a targetoid appearance on gadoxetic acid-enhanced MRI. An intratumoural septum and non-targetoid restriction as well as enhancing capsule and blood products in the mass may be useful for differentiating HCC assigned to LR-M from non-HCC malignancy on gadoxetic acid-enhanced MRI.

Longitudinal Monitoring of Gd-DTPA Following Convection Enhanced Delivery in the Brainstem.

BACKGROUND: Convection-enhanced delivery (CED) has been introduced into contemporary therapeutic strategies for incurable brain neoplasms as diffuse intrinsic pontine glioma. Therapeutic benefit in part is predictably dependent on drug distribution within tumors. However, therapeutics can rarely be detected through conventional imaging techniques. Coinfusion of the tracer gadolinium-diethylenetriaminepentacetate (Gd-DTPA) has been advocated to monitor drug distributive features including volume, tumor coverage, and efflux during and after administration. The kinetics of Gd-DTPA are unclear as longitudinal magnetic resonance imaging is rarely performed. Understanding these changes would have important implications related to the timing of diagnostic imaging and reliance on tracers as surrogates of pharmacokinetic drug monitoring. CASE DESCRIPTION: The behavior of Gd-DTPA as a surrogate is presented in a time-dependent fashion as measured by repeated magnetic resonance imaging based on the case of a child with recurrent diffuse intrinsic pontine glioma treated with an oncolytic virus (ICOVIR-5) delivered by CED with coinfused Gd-DTPA (1 mM, for a volume of 2000 µL). Initial Vd/Vi was 1.46. Gd-DTPA was observed up to 18 hours post CED but not thereafter. CONCLUSIONS: This longitudinal imaging assessment provides a rare opportunity to better characterize the kinetics of surrogate tracers delivered by CED to the brainstem, highlighting the importance of immediate and longitudinal monitoring.

Image quality of hip MR arthrography with intra-articular injection of hyaluronic acid versus gadolinium-based contrast agent in patients with femoroacetabular impingement.

OBJECTIVE: To compare image quality of magnetic resonance arthrography (MRA) of the hip with intra-articular injection of high-viscosity hyaluronic acid (HA-MRA) versus Gd-based contrast agent (Gd-MRA) in patients with femoroacetabular impingement (FAI). MATERIALS AND METHODS: Design: single-centre, observational, retrospective, inter-individual, and cross-sectional. FAI patients who underwent HA-MRA (3 mL of high-viscosity HA plus 17 mL of saline) were compared with 37 age- and sex-matched FAI patients who underwent Gd-MRA (20 mL of 2 mmol/L solution of gadopentetate dimeglumine). Two independent blinded radiologists assessed image quality for all sequences (two-dimensional proton density, non-fat-sat axial, fat-sat coronal and sagittal; three-dimensional dual-echo steady state), using a 5-point Likert scale considering separately labrum, cartilage, round ligament, transverse ligament, and capsule. Pearson χ2 and Cohen κ were used. RESULTS: The HA-MRA group was composed of 37 patients (23 males, 14 females; median age 38 years), the Gd-MRA group of 37 patients (21 males, 16 females; median age 38 years), without significant difference for age (p = 0.937) and sex (p = 0.636). Image quality did not differ between the two readers for any structure: labrum (p ≥ 0.340), cartilage (p ≥ 0.198), round ligament (p ≥ 0.255), transverse ligament (p ≥ 0.806), and capsule (p ≥ 0.314). Inter-reader agreement (κ) ranged from 0.785 to 1.000. CONCLUSIONS: HA-MRA provided an image quality not significantly different from that of Gd-MRA. This may open the possibility of combining MRA and viscosupplementation in one single procedure.

Dose Finding Study of Gadopiclenol, a New Macrocyclic Contrast Agent, in MRI of Central Nervous System.

OBJECTIVES: The aim of this study was to determine a safe and effective dose of gadopiclenol, a new high relaxivity macrocyclic gadolinium-based contrast agent. Based on the contrast-to-noise ratio (CNR) as primary criterion, this new agent was compared with gadobenate dimeglumine in patients with contrast-enhancing central nervous system lesions. METHODS AND MATERIALS: This phase IIb international, multicenter, double-blind, randomized, controlled, parallel dose groups, and cross-over study included adult patients with known or highly suspected lesions with disrupted blood-brain barrier. Patients were randomized to 1 of 4 doses of gadopiclenol (0.025, 0.05, 0.1, 0.2 mmol/kg) and to 1 series of 2 magnetic resonance imaging scans: gadopiclenol then gadobenate dimeglumine at 0.1 mmol/kg or vice versa. The qualitative and quantitative efficacy evaluations were performed by 3 independent off-site blinded readers. Adverse events were monitored up to 1 day after second magnetic resonance imaging. RESULTS: The study population included 272 patients (58.5% females) with a mean (SD) age of 53.8 (13.6) years. The superiority of gadopiclenol over gadobenate dimeglumine was statistically demonstrated at 0.2 and 0.1 mmol/kg for all readers with an increase in CNR of more than 30% (P ≤ 0.0007). At 0.05 mmol/kg, gadopiclenol showed a CNR of similar magnitude as gadobenate dimeglumine at 0.1 mmol/kg, with no statistically significant difference. Similar results were obtained for lesion-to-brain ratio and contrast enhancement percentage, as secondary criteria. The relationship between CNR and dose of gadopiclenol was linear for all readers. Mean scores for lesion visualization variables, particularly lesion contrast enhancement, tended to be higher with gadopiclenol at 0.1 and 0.2 mmol/kg compared with gadobenate dimeglumine. All 3 readers mainly expressed an overall diagnostic preference for images with gadopiclenol at 0.1 mmol/kg (45.3%, 50.9%, or 86.8% of images) or expressed no preference (49.1%, 49.1%, or 9.4%, respectively), whereas preference for images with gadobenate dimeglumine was reported by 2 readers for 3.8% and 5.7% of the images. Predominantly, no preference was expressed when comparing images with gadopiclenol at 0.05 mmol/kg to those with gadobenate dimeglumine.Rates of adverse reactions were comparable for gadopiclenol (11.7%) and gadobenate dimeglumine (12.1%). Changes from baseline of more than 25% in serum creatinine and estimated glomerular filtration rate occurred in less than 2% of patients equally for gadopiclenol and gadobenate dimeglumine. Changes from baseline for the values of blood urea nitrogen and cystatin C were also similar between gadopiclenol and gadobenate dimeglumine. No safety concerns were detected on centralized electrocardiography readings. CONCLUSIONS: Between the doses of 0.025 and 0.2 mmol/kg of gadopiclenol, the increase in CNR is linear. Compared with gadobenate dimeglumine at 0.1 mmol/kg, the doses of 0.05 and 0.1 mmol/kg of gadopiclenol gave similar or significantly greater contrast enhancement, respectively, and thus both doses can be considered for future phase III studies.