Radiomics Analysis of MR Imaging with Gd-EOB-DTPA for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Investigation and Comparison of Different Hepatobiliary Phase Delay Times.

PURPOSE: To investigate whether the radiomics analysis of MR imaging in the hepatobiliary phase (HBP) can be used to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). METHOD: A total of 130 patients with HCC, including 80 MVI-positive patients and 50 MVI-negative patients, who underwent MR imaging with Gd-EOB-DTPA were enrolled. Least absolute shrinkage and selection operator (LASSO) regression was applied to select radiomics parameters derived from MR images obtained in the HBP 5 min, 10 min, and 15 min images. The selected features at each phase were adopted into support vector machine (SVM) classifiers to establish models. Multiple comparisons of the AUCs at each phase were performed by the Delong test. The decision curve analysis (DCA) was used to analyze the classification of MVI-positive and MVI-negative patients. RESULTS: The most predictive features between MVI-positive and MVI-negative patients included 9, 8, and 14 radiomics parameters on HBP 5 min, 10 min, and 15 min images, respectively. A model incorporating the selected features produced an AUC of 0.685, 0.718, and 0.795 on HBP 5 min, 10 min, and 15 min images, respectively. The predictive model for HBP 5 min, 10 min and 15 min showed no significant difference by the Delong test. DCA indicated that the predictive model for HBP 15 min outperformed the models for HBP 5 min and 10 min. CONCLUSIONS: Radiomics parameters in the HBP can be used to predict MVI, with the HBP 15 min model having the best differential diagnosis ability.

Radiologic-Pathologic Correlation of Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement at Gadoxetic Acid-enhanced MRI: A Multicenter Study.

Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid-enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant cirrhosis-associated nodules. Purpose To assess the distribution of pathologic diagnoses of HBP hypointense nodules without APHE at gadoxetic acid-enhanced MRI and to evaluate clinical and imaging features in differentiating their histologic grades. Materials and Methods This retrospective multicenter study included pathologic analysis-confirmed HBP hypointense nodules without APHE (≤30 mm) in patients with chronic liver disease or cirrhosis screened between January 2008 and June 2016. Central pathologic review by 10 pathologists determined final histologic grades as progressed HCC, early HCC, high-grade dysplastic nodule (DN), and low-grade DN or regenerative nodule. Gadoxetic acid-enhanced MRI features were analyzed by three radiologists. Multivariable logistic regression analyses with elastic net regularization were performed to identify clinical and imaging features for differentiating histologic grades. Results There were 298 patients (mean age, 59 years ± 10; 226 men) with 334 nodules evaluated, and progressed HCCs were diagnosed in 44.0% (147 of 334), early HCCs in 20.4% (68 of 334), high-grade DNs in 27.5% (92 of 334), and low-grade DNs or regenerative nodules in 8.1% (27 of 334). Serum α-fetoprotein level 100 ng/mL or greater (odds ratio, 2.7; P = .01) and MRI features including well-defined margin (odds ratio, 5.5; P = .003), hypointensity at precontrast T1-weighted imaging (odds ratio, 3.2; P < .001), intermediate hyperintensity at T2-weighted imaging (odds ratio, 3.4; P < .001), and restricted diffusion (odds ratio, 1.9; P = .04) were independent predictors for progressed HCC at multivariable analysis. Conclusion In patients at high risk for hepatocellular carcinoma (HCC), hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid-enhanced MRI corresponded mainly to progressed HCCs, early HCCs, and high-grade dysplastic nodules. High α-fetoprotein level and some imaging features at MRI helped to differentiate progressed HCC from lower grade nodules. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Motosugi in this issue.

Gadoxetic Acid-enhanced MRI of Hepatocellular Carcinoma: Value of Washout in Transitional and Hepatobiliary Phases.

Background Current Liver Imaging Reporting and Data System guidelines define the washout appearance of gadoxetic acid-enhanced MRI only during the portal venous phase. Defining washout only during the portal venous phase may lead to lower sensitivity for diagnosis of hepatocellular carcinoma (HCC). Purpose To compare the diagnostic performances of three gadoxetic acid-enhanced MRI criteria for HCC according to the phases during which washout appearance was determined. Materials and Methods In this retrospective study, patients with a hepatic nodule detected at US surveillance for HCC from January to December 2012 underwent gadoxetic acid-enhanced MRI. Three diagnostic MRI criteria for HCC were defined according to the phases during which washout appearance was observed, with the presence of arterial phase hyperenhancement and hypointensity noted (a) only during the portal venous phase, with washout confined to the portal venous phase; (b) during the portal venous phase or transitional phase, with washout extended to the transitional phase; or (c) during the portal venous, transitional, or hepatobiliary phase, with washout extended to the hepatobiliary phase. If a nodule showed marked T2 hyperintensity or a targetoid appearance, it was precluded from the diagnosis of HCC. The sensitivity and specificity were compared by using a generalized estimating equation. Results A total of 178 patients were included (mean age ± standard deviation, 55.3 years ± 9.1) with 203 surgically confirmed hepatic nodules (186 HCCs and 17 non-HCCs) measuring 3.0 cm or smaller. The sensitivity with washout extended to the hepatobiliary phase (95.2% [177 of 186]) was better than that with washout extended to the transitional phase (90.9% [169 of 186]; P = .01) and washout confined to the portal venous phase (75.3% [140 of 186]; P < .01). The specificity with extensions of washout to the transitional phase and hepatobiliary phase (82% [14 of 17] for both) was similar to that obtained with washout confined to the portal venous phase (94.1% [16 of 17]) (P = .47). Conclusion After exclusion of typical hemangiomas and nodules with a targetoid appearance, extending washout appearance to the transitional or hepatobiliary phase (instead of restricting it to the portal venous phase) allowed higher sensitivity without a reduction in specificity. © RSNA, 2019 See also the editorial by Fowler and Sirlin in this issue.

Radiomics Analysis of Gadoxetic Acid-enhanced MRI for Staging Liver Fibrosis.

Purpose To develop and validate a radiomics-based model for staging liver fibrosis by using gadoxetic acid-enhanced hepatobiliary phase MRI. Materials and Methods In this retrospective study, 436 patients (mean age, 51 years; age range, 18-86 years; 319 men [mean age, 51 years; age range, 18-86 years]; 117 women [mean age, 50 years; age range, 18-79 years]) with pathologic analysis-proven liver fibrosis who underwent gadoxetic acid-enhanced MRI from June 2015 to December 2016 were randomized in a three-to-one ratio into development (n = 329) and test (n = 107) cohorts, respectively. In the development cohort, a model was developed to calculate radiomics fibrosis index (RFI) by using logistic regression with elastic net regularization to differentiate stage F3-F4 from stage F0-F2. Optimal RFI cutoffs to diagnose clinically significant fibrosis (stage F2-F4), advanced fibrosis (stage F3-F4), and cirrhosis (stage F4) were determined by receiver operating characteristic curve analysis. In the test cohort, the diagnostic performance of RFI was compared with that of normalized liver enhancement, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index by using the Obuchowski index. Results In the test cohort, RFI (Obuchowski index, 0.86) significantly outperformed normalized liver enhancement (Obuchowski index, 0.77; P < .03), APRI (Obuchowski index, 0.60; P < .001), and fibrosis-4 index (Obuchowski index, 0.62; P < .001) for staging liver fibrosis. By using the cutoffs, RFI had sensitivities and specificities as follows: 81% (95% confidence interval: 71%, 89%) and 78% (95% confidence interval: 63%, 89%) for diagnosing stage F2-F4, respectively; 79% (95% confidence interval: 67%, 88%) and 82% (95% confidence interval: 69%, 91%), respectively, for diagnosing stage F3-F4; and 92% (95% confidence interval: 79%, 98%) and 75% (95% confidence interval: 62%, 83%), respectively, for diagnosing stage F4. Conclusion Radiomics analysis of gadoxetic acid-enhanced hepatobiliary phase images allows for accurate diagnosis of liver fibrosis. © RSNA, 2018 Online supplemental material is available for this article.

LI-RADS Classification and Prognosis of Primary Liver Cancers at Gadoxetic Acid-enhanced MRI.

Purpose To (a) evaluate the postsurgical prognostic implication of the Liver Imaging Reporting and Data System (LI-RADS) categories of primary liver cancers and (b) determine the performance of LI-RADS version 2017 in differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (IHCC) and combined hepatocellular-cholangiocarcinoma (cHCC-CC) at gadoxetic acid-enhanced MRI. Materials and Methods In this retrospective study, 194 patients with cirrhosis and surgically proven single primary liver cancer (53 with cHCC-CC, 44 with IHCC, and 97 with HCC) were evaluated with gadoxetic acid-enhanced MRI between 2009 and 2014. The mean patient age was 57 years (age range, 30-83 years). There were 155 men with a mean age of 56 years (range, 30-81 years) and 39 women with a mean age of 58 years (range, 38-83 years). Two independent readers assigned an LI-RADS category for each nodule. Overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated by using the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. Results In the multivariable analysis, the LI-RADS category was an independent factor for OS (hazard ratio, 4.2; P < .001) and RFS (hazard ratio, 2.6; P = .01). The LR-M category showed more correlation with poorer OS and RFS than did the LR-4 or LR-5 category for all primary liver cancers (P < .001 for both), HCCs (P = .01 and P < .001, respectively), and cHCC-CCs (P = .01 and P = .03, respectively). The LR-5 category had a sensitivity of 69% (67 of 97) and a specificity of 87% (84 of 97) in the diagnosis of HCC; most false-positive diagnoses (85%, 11 of 13) were the result of misclassification of cHCC-CCs. Conclusion The Liver Imaging Reporting and Data System (LI-RADS) category was associated with postsurgical prognosis of primary liver cancers, independent of pathologic diagnosis. The LI-RADS enabled the correct classification of most hepatocellular carcinomas (HCCs) and intrahepatic cholangiocarcinomas, whereas differentiation of combined hepatocellular-cholangiocarcinoma from HCC was unreliable. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Bashir and Chernyak in this issue.

Quantitative Assessment of Liver Function by Using Gadoxetic Acid-enhanced MRI: Hepatocyte Uptake Ratio.

Purpose To determine whether hepatocyte uptake ratios derived at gadoxetic acid-enhanced MRI correlate with quantitative measures of liver function and can help to identify contraindication to major hepatectomy. Materials and Methods Between August 2016 and October 2016, 50 study participants with chronic liver disease or cirrhosis underwent liver MRI at 3.0 T including T1 mapping and elastography. Liver function was quantitatively assessed by using the indocyanine green retention test (ICG R15). T1 maps were obtained by using the Look-Locker sequence before and 10 minutes after gadoxetic acid administration (0.025 mmol/kg). The relationship between ICG R15 and the following MRI parameters was evaluated: pre- and postcontrast T1 values of the liver, hepatocyte uptake ratio representing the amount of contrast media solely taken into hepatocytes, liver volume, and degree of enhancement at the common bile duct. Diagnostic performance of the hepatocyte uptake ratio to identify patients with ICG R15 greater than 20% (ie, contraindication to hepatectomy) was compared with other parameters by using areas under the receiver operating characteristic curve. Results Hepatocyte uptake ratio showed a negative correlation with ICG R15 r of -0.78 (P < .001). In participants with chronic liver disease or Child-Pugh class A, those with ICG R15 of 20% or less showed higher hepatocyte uptake ratio than those with ICG R15 greater than 20% (P < .001). Hepatocyte uptake ratios demonstrated better performance for helping to detect ICG R15 greater than 20% than did liver volume (area under the curve, 0.96 vs 0.70; P = .01). Conclusion Hepatocyte uptake ratios are negatively correlated with liver function as measured by indocyanine green retention test and provide acceptable diagnostic performance for helping to identify participants who have contraindications to major hepatectomy. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Reeder in this issue.

Gadopentatic acid affects in vitro proliferation and doxorubicin response in human breast adenocarcinoma cells.

Contrasting agents (CAs) that are administered to patients during magnetic resonance imaging to facilitate tumor identification are generally considered harmless. However, gadolinium (Gd) based contrast agents can be retained in the body, inflicting specific cell line cytotoxicity. We investigate the effect of Gadopentatic acid (Gd-DTPA) on human breast adenocarcinoma MCF-7 cells. These cells exhibit a toggle switch response: exposure to 0.1 and 1 mM concentrations of Gd-DTPA enhances proliferation, which is hindered at a higher 10 mM concentration. Proliferation is enhanced when cells transition to 3D morphologies in post confluent conditions. The proliferation dependence on the concentration of CA is absent for Hs 578T and MDA-MB-231 triple negative cell lines. MCF-7 cells reveal a double toggle switch related to the expression of VEGF, which goes through high-low-high downregulation when cells are exposed to 0.1, 1, and 10 mM Gd-DTPA, respectively. Finally, doxorubicin drug response is assessed, which also reveals a double toggle switch behavior, where drug cytotoxicity exhibits a nonlinear dependence on the CA concentration. A toggle switch in cell characteristics that are exposed to 1 mM of Gd-DTPA amplifies the importance of this threshold, affecting several cell behaviors if surpassed. This work emphasizes the important effects that CAs can have on cells, specifically Gd-DTPA on MCF-7 cells, and the implications for cell growth and drug response during clinical and synthetic biology procedures.

Imaging Features of Gadoxetic Acid-enhanced and Diffusion-weighted MR Imaging for Identifying Cytokeratin 19-positive Hepatocellular Carcinoma: A Retrospective Observational Study.

Purpose To determine the preoperative magnetic resonance (MR) imaging findings potentially most useful for predicting cytokeratin 19 (CK19)-positive hepatocellular carcinoma (HCC) and to evaluate the prognosis after curative resection in patients with a single HCC lesion positive for CK19 compared with patients with HCC who are negative for CK19. Materials and Methods The institutional review board approved this study and waived the requirement for informed consent. Two hundred four patients with CK19-negative HCC and 38 with CK19-positive HCC who underwent curative resection after gadoxetic acid-enhanced and diffusion-weighted MR imaging were retrospectively evaluated in a single institution. Two radiologists evaluated preoperative findings at MR imaging. Significant findings for differentiating the two groups were identified at univariate and multivariate analyses. By using receiver operating characteristic analysis, the optimal cut-off values for quantitative variables were determined. Recurrence-free survival rates after surgery were also compared between groups. Results At multivariate analysis, irregular tumor margin (P = .024), arterial rim enhancement (P < .001), lower tumor-to-liver signal intensity (SI) ratio on hepatobiliary phase (HBP) images (≤0.522; P = .01), and lower tumor-to-liver apparent diffusion coefficient (ADC) ratio (≤0.820; P < .001) were independent significant factors to predict CK19-positive HCC. When three of these four criteria were combined, 63.2% (24 of 38; 95% confidence interval: 46.0%, 78.2%) of CK19-positive HCCs were identified with a specificity of 90.7% (185 of 204; 95% confidence interval: 46.0%, 78.2%). When all four criteria were satisfied, specificity was 99.5% (203 of 204; 95% confidence interval: 97.3%, 100%). Recurrence-free survival rates were significantly lower in patients with CK19-positive HCCs compared with those with CK19-negative HCCs after curative resection (63.9% vs 90.0% at 1 year, 63.9% vs 79.9% at 2 years, and 54.8% vs 70.2% at 3 years, P = .001 by log-rank test). Conclusion At gadoxetic acid-enhanced and diffusion-weighted MR imaging, irregular margin, arterial phase rim enhancement, lower tumor-to-liver ADC ratio, and lower tumor-to-liver SI ratio at HBP imaging may be helpful to predict CK19-positive HCC with early recurrence (<2 years) after curative resection. © RSNA, 2017 Online supplemental material is available for this article.

Diagnostic Value of Gadoxetic Acid-Enhanced MR Imaging to Distinguish HCA and Its Subtype from FNH: A Systematic Review.

Objective: The purpose of this study was to systematically review the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) for differentiation of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH), as well as HCA classification by using the low signal intensity (SI) in the hepatobiliary phase (HBP). Methods: A systematic process was used to review all published data in MEDLINE database about Gd-EOB-DTPA-MRI applied to differentiation of HCA and FNH, and classification of HCA by using low SI in the HBP. The pooled sensitivity and specificity were calculated to assess the diagnostic value of low SI in the HBP. Results: A review of 45 articles identified 10 eligible studies with a total of 288 HCA lesions. The pooled proportion of low SI in the HBP of HCA were 91% (95% CI: 0.81-0.97). In specific, the subtypes of HCA were 75% (95% CI: 0.64-0.85) for I-HCA, 100% (95% CI: 0.95-1.00) for H-HCA, 92% (95% CI: 0.70-1.00) for U-HCA, and 59% (95% CI: 0.00-1.00) for b-HCA, respectively. The pooled specificity and sensitivity of low SI in the HBP for distinguishing FNH from HCA were 95% (95% CI: 0.92-0.98) and 92% (95% CI: 0.87-0.96), respectively. Conclusion: Low SI in the HBP of Gd-EOB-DTPA-MRI is associated with higher accuracy for distinguishing HCA from FNH. However, the diagnostic accuracy may be overvalued, especially for the diagnosis of subtypes of b-HCA and I-HCA. Therefore, the risk factors and conventional imaging findings should be take into account simultaneously.

Diagnostic Performance of Gadoxetic Acid-enhanced Liver MR Imaging versus Multidetector CT in the Detection of Dysplastic Nodules and Early Hepatocellular Carcinoma.

Purpose To compare the diagnostic performance of gadoxetic acid-enhanced liver magnetic resonance (MR) imaging with that of contrast material-enhanced multidetector computed tomography (CT) in the detection of borderline hepatocellular nodules in patients with liver cirrhosis and to determine the Liver Imaging Reporting and Data System (LI-RADS) categories of these detected nodules. Materials and Methods The institutional review board approved this retrospective study and waived the informed consent requirement. Sixty-eight patients with pathologically proven dysplastic nodules (DNs) (low-grade DNs, n = 20; high-grade DNs, n = 17), early hepatocellular carcinomas (HCCs) (n = 42), or progressed HCCs (n = 33) underwent gadoxetic acid-enhanced MR imaging and multidetector CT. An additional 57 patients without any DNs or HCCs in the explanted livers were included as control subjects. Three radiologists independently graded the presence of liver nodules on a five-point confidence scale and assigned LI-RADS categories by using imaging findings. Jackknife alternative free-response receiver operating characteristics (JAFROC) software was used to compare the diagnostic accuracy of each modality in lesion detection. Results Reader-averaged figures of merit estimated with JAFROC software to detect hepatocellular nodules were 0.774 for multidetector CT and 0.842 for MR imaging (P = .002). Readers had significantly higher detection sensitivity for early HCCs with MR imaging than with multidetector CT (78.6% vs 52.4% [P = .001], 71.4% vs 50.0% [P = .011], and 73.8% vs 50.0% [P = .001], respectively). A high proportion of overall detected early HCCs at multidetector CT (59.4%) and MR imaging (72.3%) were categorized as LI-RADS category 4. Most early HCCs (76.2%) and high-grade DNs (82.4%) demonstrated hypointensity on hepatobiliary phase images. In total, 30 more LI-RADS category 4 early HCCs were identified with MR imaging than with multidetector CT across all readers. Conclusion Gadoxetic acid-enhanced MR imaging performed significantly better in the detection of high-risk borderline nodules, especially early HCCs, than did multidetector CT. © RSNA, 2017 Online supplemental material is available for this article.

Hepatic function imaging using dynamic Gd-EOB-DTPA enhanced MRI and pharmacokinetic modeling.

PURPOSE: To determine whether pharmacokinetic modeling parameters with different output assumptions of dynamic contrast-enhanced MRI (DCE-MRI) using Gd-EOB-DTPA correlate with serum-based liver function tests, and compare the goodness of fit of the different output assumptions. METHODS: A 6-min DCE-MRI protocol was performed in 38 patients. Four dual-input two-compartment models with different output assumptions and a published one-compartment model were used to calculate hepatic function parameters. The Akaike information criterion fitting error was used to evaluate the goodness of fit. Imaging-based hepatic function parameters were compared with blood chemistry using correlation with multiple comparison correction. RESULTS: The dual-input two-compartment model assuming venous flow equals arterial flow plus portal venous flow and no bile duct output better described the liver tissue enhancement with low fitting error and high correlation with blood chemistry. The relative uptake rate Kir derived from this model was found to be significantly correlated with direct bilirubin (r = -0.52, P = 0.015), prealbumin concentration (r = 0.58, P = 0.015), and prothrombin time (r = -0.51, P = 0.026). CONCLUSION: It is feasible to evaluate hepatic function by proper output assumptions. The relative uptake rate has the potential to serve as a biomarker of function. Magn Reson Med 78:1488-1495, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

The utility of gadoxetic acid-enhanced magnetic resonance imaging in the surveillance for postoperative recurrence of hepatocellular carcinoma.

This study aimed to investigate the utility of gadoxetic acid-enhanced magnetic resonance imaging (Gd-MRI) in surveillance for recurrent hepatocellular carcinoma (HCC) after hepatectomy.This retrospective study analyzed 147 patients who underwent surveillance with alternating multidetector computed tomography (MDCT) and Gd-MRI after hepatectomy for HCC. The patients were followed-up every 3 months during the first 2 years, and every 6 months thereafter. At each visit, MDCT was performed but once a year (every 12 months), Gd-MRI was performed instead of MDCT. Each HCC recurrence detection rate of MDCT and Gd-MRI was evaluated, and recurrent HCC characteristics were compared according to the detection test.A total of 63 patients had recurrent HCC. Among them, 9 were detected with Gd-MRI and 29 with MDCT. The baseline characteristics of patients with recurrent HCC showed no significant differences according to the detection test. The HCC recurrence detection rate of Gd-MRI and MDCT was 4.8% (9/180) and 4.3% (29/580), respectively, on the per test basis (P = 0.764). However, in the population with a follow-up period of ≥12 months, the detection rate of Gd-MRI and MDCT was 4.3% (7/150) and 1.5% (19/400), respectively (P = 0.035). Recurrent HCCs detected with Gd-MRI were smaller than those detected with MDCT (tumor size < 2 cm, 100% vs 65.5%, P = 0.040).Our data suggest that Gd-MRI has advantages in detecting recurrent HCC after hepatectomy. Surveillance with alternating MDCT and Gd-MRI may identify more recurrent HCC in an early stage than with MDCT alone in patients who received hepatectomy for HCC.

Nano assembly and encapsulation; a versatile platform for slowing the rotation of polyanionic Gd(3+) -based MRI contrast agents.

Encapsulating discrete Gd(3+) chelates in nano-assembled capsules (NACs) is a simple and effective method of preparing an MRI contrast agent capable of delivering a large payload of high relaxivity imaging agent. The preparation of contrast agent containing NACs had previously focussed on preparations incorporating GdDOTP(5-) into the internal aggregate. In this report we demonstrate that other Gd(3+) chelates bearing overall charges as low as 2- can also be used to prepare NACs. This discovery opens up the possibility of using Gd(3+) chelates that have inner-sphere water molecules that could further increase the relaxivity enhancement associated with the long τR that arises from encapsulation. However, encapsulation of the q = 1 chelate GdDTPA(2-) did not give rise to a significant increase in relaxivity relative to encapsulation of the outer-sphere chelate GdTTHA(3-). This leads us to the conclusion that in the NAC interior proton transport is not mediated by movement of whole water molecules and the enhanced relaxivity of Gd(3+) chelate encapsulated within NACs arises primarily from second sphere effects.

Validation of 10-Minute Delayed Hepatocyte Phase Imaging with 30° Flip Angle in Gadoxetic Acid-Enhanced MRI for the Detection of Liver Metastasis.

OBJECTIVES: To compare 10-minute delayed hepatocyte phase imaging using a 30° flip angle (10 min-FA30) and 20-minute hepatocyte phase imaging using a 10° FA (20 min-FA10) in gadoxetic acid-enhanced MRI of patients with possible liver metastases, regarding lesion-to-liver contrast-to-noise ratio (CNR) and focal hepatic lesion (FHL) detection to evaluate whether 10 min-FA30 would be superior to 20 min-FA10. MATERIALS AND METHODS: Eighty-three patients with 248 liver metastases and 78 benign FHLs who underwent gadoxetic acid-enhanced MRI with 10 min-FA30 and 20 min-FA10 were enrolled. Lesion-to-liver CNRs were compared between the two image groups. Two radiologists independently assessed the presence of FHLs using a four-point scale and detection sensitivity was calculated. RESULTS: The mean CNR for liver metastases on the 10 min-FA30 (248.5 ± 101.6) were significantly higher than that of the 20 min-FA10 (187.4 ± 77.4) (p < 0.001). The mean CNR difference between the two image groups was 61.2 ± 56.8. There was no significant difference in detection sensitivity of FHLs for two readers between 10 min-FA30 (mean 97.7%) and 20 min-FA10 (mean 97.9%), irrespective of the lesion size or malignancy. CONCLUSION: 10 min-FA30 yielded higher CNR with similar sensitivity compared to 20 min-FA10. This finding indicates that 10 min-FA30 can potentially replace 20 min-FA10 with higher diagnostic performance and save 10 minutes of time.

Antitumor efficacy of extracellular complexes with gadolinium in Binary Radiotherapy.

In this report the efficacy of extracellular pharmaceutical Gd-DTPA in Binary Radiotherapy was studied. The study was carried out in mice bearing transplantable adenocarcinoma Ca755 using X-ray based contrast enhanced radiotherapy as a practical implementation of Binary Radiotherapy. It was shown that intravenous administration of 0.3 ml of 0.5 M water solution of Gd-DTPA followed by X-irradiation at a dose of 10 Gy provides T/C%=10±3% and leads to complete tumor regression in 25% of mice.

Safety of gadoxetate disodium: Results from the clinical phase II-III development program and postmarketing surveillance.

PURPOSE: To summarize the safety data of gadoxetate disodium, reported in 12 Phase II and III clinical development studies and in the postmarketing surveillance database. MATERIALS AND METHODS: Patients with liver lesions received gadoxetate disodium-enhanced liver magnetic resonance imaging (MRI). Adverse events (AEs) were recorded and evaluated with regard to a potential drug relationship. Subgroup analyses were run on patients with special medical history. Worldwide spontaneous AEs and adverse drug reactions (ADRs) from postmarketing safety surveillance were analyzed. RESULTS: A total of 1989 patients were included in the clinical development program. A total of 1581/1989 (79.5%) patients received the finally approved dose of 0.025 mmol/kg body weight. 10.1% of patients reported AEs, 4.1% were classified as related AEs. Nausea and headache were the most frequently reported related AEs, with 1.1% each. Age, history of contrast media allergy, liver cirrhosis, or impaired liver or renal function did not significantly impact the frequency and type of AEs. The postmarketing safety surveillance database encompassed more than 2.2 million patients. Nausea was the most frequent ADR, with a reporting rate of 0.00652%; all other symptoms were below 0.004%. CONCLUSION: Gadoxetate disodium for liver MRI has an excellent safety profile.

Analysis of whole blood samples with low gas flow inductively coupled plasma-optical emission spectrometry.

Low gas flow ICP-OES with a total argon consumption below 0.7 L/min is introduced for the analysis of trace elements in blood samples to investigate the influence of samples containing an organic solvent in a demanding matrix on the performance of this plasma for the first time. Therefore, gadolinium was determined in human plasma samples and mercury in red blood cells, human plasma, and precipitated plasma protein fraction. Limits of detection (LOD) were determined to be in the low microgram per liter range for the analytes and the accuracy of the method was assessed by comparison with a conventional Fassel-type torch-based ICP-OES. It was proven that the low gas flow ICP-OES leads to comparable results with the instrument based on the Fassel-type torch.

Biologic properties of gadolinium diethylenetriaminepentaacetic acid-labeled and PKH26-labeled human umbilical cord mesenchymal stromal cells.

BACKGROUND AIMS: This study was conducted to characterize gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-labeled and PKH26-labeled human umbilical cord mesenchymal stromal cells (HuMSCs) and to track them with magnetic resonance imaging (MRI) in vitro and in vivo. METHODS: HuMSCs were isolated from umbilical cords and expanded in vitro. Cells were sequentially labeled with Gd-DTPA and PKH26. The labeling efficiency was determined by spectrophotometry measurements, and the longevity of Gd-DTPA maintenance was measured with MRI. The influence of double labeling on cellular biologic properties was assessed by cell proliferation, viability, differentiation, cycle and apoptosis. Transplantation of double-labeled HuMSCs or placebo was performed in 39 female Sprague-Dawley rats. Leak point pressure and maximal bladder capacity were measured in animals 6 weeks after injection. RESULTS: The T1 values and signal intensity on T1-weighted imaging of labeled cells were significantly higher than the control group (P < 0.05). The signal intensity on T1-weighted imaging of labeled cells was retained >14 days in vitro and in vivo. There was no significant difference in the cell cycle, cell apoptosis, cell proliferation and cell viability between labeled and unlabeled HuMSCs (P > 0.05). After double labeling, HuMSCs were still capable of differentiating into osteoblasts and adipocytes. Periurethrally injected HuMSCs in the rats significantly improved leak point pressure and maximal bladder capacity. CONCLUSIONS: HuMSCs were successfully labeled with Gd-DTPA and PKH26. This labeling method is reliable and efficient and can be applied for tracking cells in vitro and in vivo without altering cellular biologic properties.

Estimated background doses of [67Ga]-DTPA-USPIO in normal Balb/c mice as a potential therapeutic agent for liver and spleen cancers.

INTRODUCTION: The aim of this study was to evaluate the biodistribution of dextran-coated iron oxide nanoparticles labeled with gallium-67 (Ga) in various organs by intravenous injection in Balb/c mice. METHODS: Ultrasmall superparamagnetic iron oxide (USPIO) was successively labeled with Ga-chloride after chelation with freshly prepared cyclic DTPA-dianhydride. The labeling efficiency of USPIOs labeled with Ga is above 98%. Sixty-five mice were killed at 13 different time points. The percentage of injected dose per gram of each organ was measured by direct counting for 19 harvested organs of the mice. The medical internal radiation dose formula was applied to extrapolate data from mouse to human and to predict the absorbed radiation dose for various organs in the human body. RESULTS: The biodistribution of Ga-USPIO in Balb/c mice showed that 75% of the injected dose accumulated in the spleen and liver 15 min after injection. These nanoparticles remained in the liver for more than 7 days after injection, whereas their clearance was very fast from other organs. Extrapolating these data to the intravenous injection of Ga-USPIO in humans gave an estimated absorbed dose of 36.38 mSv/MBq for the total body, and the highest effective absorbed dose was seen in the liver (32.9 mSv/MBq). CONCLUSION: High uptakes of USPIO nanoparticles in the liver and spleen and their fast clearance from other tissues suggest that these nanoparticles labeled with a ß-emitter radioisotope could be suitable as treatment agents for spleen and liver malignancies only if the organ tolerance dose is not exceeded.

Use of cardiac MR imaging to evaluate the presence of myocarditis in autoimmune myositis: three cases.

Cardiac involvement in patients with idiopathic inflammatory myopathies (autoimmune myositis) is important to detect because it confers an increased risk of mortality. However, detection of myocardial involvement is hampered by a lack of sensitivity of traditional non-invasive methods, and the finding of elevated cardiac troponin T levels that may be due to regenerating skeletal muscle, rather than myocardial damage. Here, we describe three cases of inflammatory myositis with elevated troponin T levels, and non-specific echocardiographic and ECG findings. Cardiac MR imaging was useful in the evaluation for the presence of myocarditis or alternative cardiac pathology.