Gadoxetic Acid-enhanced Hepatobiliary Phase Research Articles

Breath-hold High-resolution T1-weighted Gradient Echo Liver MR Imaging with Compressed Sensing Obtained during the Gadoxetic Acid-enhanced Hepatobiliary Phase: Image Quality and Lesion Visibility Compared with a Standard T1-weighted Sequence.

To evaluate the feasibility of breath-hold (BH) high-resolution (HR) T1-weighted gradient echo hepatobiliary phase (HBP) imaging using compressed sensing (CS) in gadoxetic acid-enhanced liver MRI in comparison with standard HBP imaging using parallel imaging (PI). The study included 122 patients with liver tumors with hypointensity in the HBP who underwent both HR HBP imaging with CS and standard HBP imaging with PI. Two radiologists evaluated the liver edge sharpness, hepatic vessel conspicuity, bile duct conspicuity, image noise, and overall image quality, as well as the lesion conspicuity on HR and standard HBP imaging and the contrast-enhanced (CE) MR cholangiography (MRC) image quality reconstructed from HBP images. As a quantitative analysis, the SNR of the liver and the liver to lesion signal intensity ratio (LLSIR) were also determined. The liver edge sharpness, hepatic vessel conspicuity, bile duct conspicuity, and overall image quality as well as the lesion conspicuity and the LLSIR on HR HBP imaging with CS were significantly higher than those on standard HBP imaging (all of P < 0.001). The image quality of CE-MRC reconstructed from HR HBP imaging with CS was also significantly higher than that from standard HBP imaging (P < 0.001). Conversely, the SNR of liver in standard HBP was significantly higher than that in HR HBP with CS (P < 0.001). BH HR HBP imaging with CS provided an improved overall image quality, lesion conspicuity, and CE-MRC visualization when compared with standard HBP imaging without extending the acquisition time.

Deep Learning-Based Assessment of Functional Liver Capacity Using Gadoxetic Acid-Enhanced Hepatobiliary Phase MRI.

ObjectiveWe aimed to develop and test a deep learning algorithm (DLA) for fully automated measurement of the volume and signal intensity (SI) of the liver and spleen using gadoxetic acid-enhanced hepatobiliary phase (HBP)-magnetic resonance imaging (MRI) and to evaluate the clinical utility of DLA-assisted assessment of functional liver capacity.Materials and MethodsThe DLA was developed using HBP-MRI data from 1014 patients. Using an independent test dataset (110 internal and 90 external MRI data), the segmentation performance of the DLA was measured using the Dice similarity score (DSS), and the agreement between the DLA and the ground truth for the volume and SI measurements was assessed with a Bland-Altman 95% limit of agreement (LOA). In 276 separate patients (male:female, 191:85; mean age ± standard deviation, 40 ± 15 years) who underwent hepatic resection, we evaluated the correlations between various DLA-based MRI indices, including liver volume normalized by body surface area (LVBSA), liver-to-spleen SI ratio (LSSR), MRI parameter-adjusted LSSR (aLSSR), LSSR × LVBSA, and aLSSR × LVBSA, and the indocyanine green retention rate at 15 minutes (ICG-R15), and determined the diagnostic performance of the DLA-based MRI indices to detect ICG-R15 ≥ 20%.ResultsIn the test dataset, the mean DSS was 0.977 for liver segmentation and 0.946 for spleen segmentation. The Bland-Altman 95% LOAs were 0.08% ± 3.70% for the liver volume, 0.20% ± 7.89% for the spleen volume, -0.02% ± 1.28% for the liver SI, and -0.01% ± 1.70% for the spleen SI. Among DLA-based MRI indices, aLSSR × LVBSA showed the strongest correlation with ICG-R15 (r = -0.54, p < 0.001), with area under receiver operating characteristic curve of 0.932 (95% confidence interval, 0.895–0.959) to diagnose ICG-R15 ≥ 20%.ConclusionOur DLA can accurately measure the volume and SI of the liver and spleen and may be useful for assessing functional liver capacity using gadoxetic acid-enhanced HBP-MRI.

Prediction of Decompensation and Death in Advanced Chronic Liver Disease Using Deep Learning Analysis of Gadoxetic Acid-Enhanced MRI.

This study aimed to evaluate the usefulness of quantitative indices obtained from deep learning analysis of gadoxetic acid-enhanced hepatobiliary phase (HBP) MRI and their longitudinal changes in predicting decompensation and death in patients with advanced chronic liver disease (ACLD). We included patients who underwent baseline and 1-year follow-up MRI from a prospective cohort that underwent gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance between November 2011 and August 2012 at a tertiary medical center. Baseline liver condition was categorized as non-ACLD, compensated ACLD, and decompensated ACLD. The liver-to-spleen signal intensity ratio (LS-SIR) and liver-to-spleen volume ratio (LS-VR) were automatically measured on the HBP images using a deep learning algorithm, and their percentage changes at the 1-year follow-up (ΔLS-SIR and ΔLS-VR) were calculated. The associations of the MRI indices with hepatic decompensation and a composite endpoint of liver-related death or transplantation were evaluated using a competing risk analysis with multivariable Fine and Gray regression models, including baseline parameters alone and both baseline and follow-up parameters. Our study included 280 patients (153 male; mean age ± standard deviation, 57 ± 7.95 years) with non-ACLD, compensated ACLD, and decompensated ACLD in 32, 186, and 62 patients, respectively. Patients were followed for 11-117 months (median, 104 months). In patients with compensated ACLD, baseline LS-SIR (sub-distribution hazard ratio [sHR], 0.81; p = 0.034) and LS-VR (sHR, 0.71; p = 0.01) were independently associated with hepatic decompensation. The ΔLS-VR (sHR, 0.54; p = 0.002) was predictive of hepatic decompensation after adjusting for baseline variables. ΔLS-VR was an independent predictor of liver-related death or transplantation in patients with compensated ACLD (sHR, 0.46; p = 0.026) and decompensated ACLD (sHR, 0.61; p = 0.023). MRI indices automatically derived from the deep learning analysis of gadoxetic acid-enhanced HBP MRI can be used as prognostic markers in patients with ACLD.

Uptake of gadoxetic acid in hepatobiliary phase magnetic resonance imaging and transporter expression in hypovascular hepatocellular nodules

AimsTo evaluate the association between contrast patterns on gadoxetic acid-enhanced hepatobiliary phase (HBP) MR images and transporter expression in surgically resected hypovascular hepatocellular nodules including early hepatocellular carcinomas (HCCs). MethodsForty-two hypovascular hepatic nodules and 43 hypervascular HCCs as a control were included in this retrospective study. Contrast of the nodules on HBP images was graded as hypo-, iso-, or hyperintense. Histopathological assessment was performed in the context of multistep hepatocarcinogenesis. Immunohistochemical staining of organic anion transporter 1B3 (OATP1B3) and multidrug resistance protein 2 (MRP2) was performed. Cramer’s coefficient was used to determine the linear relationship between contrast grades and transporter expression, and the Cochran-Armitage trend test was used to determine the relationship between transporter expression and progression of multistep hepatocarcinogenesis. ResultsModerate linear relationships between contrast grades and OATP1B3 expression were observed for both hypo- and hypervascular nodules. OATP1B3 expression was negatively correlated with the progression of multistep hepatocarcinogenesis. MRP2 expression was not associated with the contrast grades or histopathological results. ConclusionOATP1B3 expression was associated with contrast grades of hepatocellular nodules observed in HBP image of gadoxetic acid-enhanced MRI in the hypovascular hepatocellular nodules and was negatively correlated with hepatocarcinogenesis.

Fully automated prediction of liver fibrosis using deep learning analysis of gadoxetic acid-enhanced MRI.

To (1) develop a fully automated deep learning (DL) algorithm based on gadoxetic acid-enhanced hepatobiliary phase (HBP) MRI and (2) compare the diagnostic performance of DL vs. MR elastography (MRE) for noninvasive staging of liver fibrosis. This single-center retrospective study included 355 patients (M/F 238/117, mean age 60 years; training, n = 178; validation, n = 123; test, n = 54) who underwent gadoxetic acid-enhanced abdominal MRI, including HBP and MRE, and pathological evaluation of the liver within 1 year of MRI. Cropped liver HBP images from a custom-written fully automated liver segmentation were used as input for DL. A transfer learning approach based on the ImageNet VGG16 model was used. Different DL models were built for the prediction of fibrosis stages F1-4, F2-4, F3-4, and F4. ROC analysis was performed to evaluate the performance of DL in training, validation, and test sets and of MRE liver stiffness in the test set. AUC values of DL were 0.99/0.70/0.77 (F1-4), 0.92/0.71/0.91 (F2-4), 0.91/0.78/0.90 (F3-4), and 0.98/0.83/0.85 (F4) for training/validation/test sets, respectively. The AUCs of MRE liver stiffness in the test set were 0.86 (F1-4), 0.87 (F2-4), 0.92 (F3-4), and 0.86 (F4). AUCs of MRE and DL were not significantly different for any of the fibrosis stages (p > 0.134). The fully automated DL models based on HBP gadoxetic acid MRI showed good-to-excellent diagnostic performance for staging of liver fibrosis, with similar diagnostic performance to MRE. After validation in independent sets, the DL algorithm may allow for noninvasive liver fibrosis assessment without the need for additional MRI hardware. • The developed deep learning algorithm, based on routine standard-of-care gadoxetic acid-enhanced MRI data, showed good-to-excellent diagnostic performance for noninvasive staging of liver fibrosis. • The diagnostic performance of the deep learning algorithm was equivalent to that of MR elastography in a separate test set.

MRI characterization of focal liver lesions in non-cirrhotic patients: assessment of added value of gadoxetic acid-enhanced hepatobiliary phase imaging

BackgroundTo evaluate the added value of the hepatobiliary (HPB) phase in gadoxetic acid-enhanced magnetic resonance imaging (MRI) in characterizing newly discovered indeterminate focal liver lesions in non-cirrhotic patients.ResultsOne-hundred and twenty-five non-cirrhotic patients (median age, 46 years; range, 20–85 years; 100 females) underwent gadoxetic acid-enhanced MRI, including the 20-min delayed HPB phase, for characterization of newly discovered focal liver lesions. Images were independently evaluated by two blinded, board-certified abdominal radiologists (R1 and R2) who characterized liver lesions without and with assessment of the HPB phase images in two separate readout sessions. Confidence in diagnosis was scored on a scale from 0 to 3. Inter-observer agreement was assessed using Cohen κ statistics. Change in diagnosis and confidence in diagnosis were evaluated by Wilcoxon signed rank test. There was no significant change in diagnosis before and after evaluation of the HPB phase for both readers (p = 1.0 for R1; p = 0.34 for R2). Confidence in diagnosis decreased from average 2.8 ± 0.45 to 2.6 ± 0.59 for R1 and increased from 2.6 ± 0.83 to 2.8 ± 0.46 for R2. Change in confidence was only statistically significant for R1 (p = 0.003) but not significant for R2 (p = 0.49). Inter-reader agreement in diagnosis was good without (k = 0.66) and with (k = 0.75) inclusion of the HPB phase images.ConclusionsThe added information obtained from the HPB phase of gadoxetic acid-enhanced MRI does not change the diagnosis or increase confidence in diagnosis when evaluating new indeterminate focal liver lesions in non-cirrhotic patients.

Radiomics Analysis of Gadoxetic Acid–enhanced MRI for Staging Liver Fibrosis

Radiomics analysis of gadoxetic acid-enhanced hepatobiliary phase images allows for accurate staging of liver fibrosis.

Predicting Patients With Insufficient Liver Enhancement in the Hepatobiliary Phase Before the Injection of Gadoxetic Acid: A Practical Approach Using the Bayesian Method.

Gadoxetic acid-enhanced hepatobiliary phase (HBP) is useful in liver MRI, but sometimes shows insufficient liver enhancement. There is no established method to predict insufficient liver enhancement before the contrast injection. To reveal the utility of the Bayesian method for predicting patients with insufficient liver enhancement in the gadoxetic acid-enhanced HBP. Retrospective. In all, 576 patients with chronic liver disease. 3T/3D gradient-echo T1 -weighted imaging and MR elastography (MRE). The patients were divided into two groups: insufficient and sufficient liver enhancement in HBP according to the liver-to-portal vein signal intensity ratio. Various parameters, including liver function tests and liver stiffness by MRE, were evaluated as predictors of insufficient liver enhancement. We used Chi-square/Student's t-test/logistic regression analysis to determine independent associates, and Bayes' theorem to estimate the probability of insufficient (or sufficient) liver enhancement. The feasibility of Bayesian prediction of insufficient liver enhancement was tested by leave-one-out cross-validation to calculate sensitivity and specificity for single variables and combinations of some variables in all patients and in a subpopulation showing a confidence level of >80%. Independent associates of insufficient liver enhancement in HBP included: serum albumin (odds ratio [OR] = 4.82, P < 0.001), total bilirubin (OR = 0.30, P < 0.00), platelet count (OR = 1.54, P < 0.00), and liver stiffness by MRE (OR = 0.59, P < 0.00). The accuracy of Bayesian prediction of insufficient liver enhancement was 80.9% (466/576) for the single parameter of albumin and 79.0% (455/576) for total bilirubin, and was increased to 85.2% (487/576) for a combination of albumin, total bilirubin, and liver stiffness. In patients who showed a confidence level of >80%, the accuracy was 89.0% (439/493) for the above combination. Bayesian prediction was useful to predict patients with insufficient enhancement by combining serum liver function tests and liver stiffness by MRE. 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:62-69.

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.

Abstract 1294: Preoperative prediction of microvascular invasion in HCC using radiomics on multisequence gadoxetic acid-enhanced MR images

Abstract Micro-vascular invasion (MVI) is underscored as a judicious risk factor for early-stage recurrence and poor prognosis of hepatocellular carcinoma (HCC). Preoperative knowledge of MVI would assist in therapy decision making beforehand, thus prolong the survival of HCC patients. However, current diagnosis of MVI could only be obtained by pathological confirmation after the surgery or through punctures, which hinders timely therapeutic regime plan or causes needless suffering for the patients. In this study, we aimed to perform a preoperative prediction on MVI using multi-sequence Radiomics on gadoxetic acid-enhanced MR images, along with multi-variable clinical factor analysis. A cohort of 208 patients diagnosed with HCC was enrolled with institutional review board approval. Radiomic features including shape and size, intensity, textural and wavelet features were extracted on segmented region of interest. The least absolute regression modeling was used to select the most effective radiomic features which had potential for MVI identification. We finally utilized logistic regression modelling to generate the single radiomics signature for each sequence with Akaike information criteria as the stopping rule. Gadoxetic acid-enhanced hepatobiliary phase (HBP) T1-weighted image and HBP T1 map turned out to be the best-performed sequences with AUC over 0.7 on both training and validation cohorts. The fusion radiomics signature incorporating effective features from these two sequences achieved the optimal prediction with AUC of 0.895 on the training cohort and 0.837 on the validation cohort. Adding the pertinent clinical and radiological factors: AFP, irregular tumor border and arterial peritumoral enhancement, the final combined model could successfully predict the MVI with AUC of 0.943 on the training cohort and 0.861 on the validation cohort. Our study revealed the archetypal radiomic features related MVI and highlighted the fusion radiomics signature as a powerful imaging marker for MVI preoperative prediction. Radiomics combined with traditional clinic-radiological information would no doubt improve the clinical decision making in HCC therapy. Citation Format: Jingwei Wei, Dongsheng Gu, Di Dong, Shuaitong Zhang, Yushen Jin, Jie Tian. Preoperative prediction of microvascular invasion in HCC using radiomics on multisequence gadoxetic acid-enhanced MR images [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1294.

Thin-slice Free-breathing Pseudo-golden-angle Radial Stack-of-stars with Gating and Tracking T1-weighted Acquisition: An Efficient Gadoxetic Acid-enhanced Hepatobiliary-phase Imaging Alternative for Patients with Unstable Breath Holding.

Purpose:To compare four free-breathing scan techniques for gadoxetic acid-enhanced hepatobiliary phase imaging with conventional breath-hold scans.Materials and Methods:Gadoxetic acid-enhanced hepatobiliary phase imaging with six image acquisition sets performed in 50 patients. Image acquisition sets included fat-suppressed 3D T1-weighted turbo field echo with free-breathing pseudo-golden-angle radial stack-of-stars (FBRS) acquisition, FBRS with track (FBRST), FBRS with gate and track (FBRSG&T), thin-slice FBRS with gate and track (thin-slice FBRSG&T), free-breathing Cartesian acquisition (CartesianFB), and breath-hold Cartesian acquisition (CartesianBH). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and image quality compared to the six-image acquisition sets.Results:Signal-to-noise ratio and CNR were significantly higher in FBRS, FBRST, FBRSG&T, and thin-slice FBRSG&T than in CartesianFB and CartesianBH (P < 0.001). Based on sharpness, motion artifacts, visibility of intrahepatic vessels, and overall image quality, thin-slice FBRSG&T had the highest image quality followed by CartesianBH and FBRSG&T (P < 0.001). Severe motion artifacts were observed in 25 patients in CartesianFB and three patients in CartesianBH, whereas image quality remained above the acceptable range in FBRSG&T, FBRST, FBRS, and thin-slice FBRSG&T in all cases.Conclusion:Thin-slice FBRSG&T demonstrated excellent image quality compared with conventional CartesianBH in gadoxetic acid-enhanced hepatobiliary phase imaging. It can be apply to supplemental sequences of patients with unstable breath holding.

Liver Fibrosis: Deep Convolutional Neural Network for Staging by Using Gadoxetic Acid-enhanced Hepatobiliary Phase MR Images.

Purpose To investigate the performance of a deep convolutional neural network (DCNN) model in the staging of liver fibrosis using gadoxetic acid-enhanced hepatobiliary phase magnetic resonance (MR) imaging. Materials and Methods This retrospective study included patients for whom input data (hepatobiliary phase MR images, static magnetic field of the imaging unit, and hepatitis B and C virus testing results available, either positive or negative) and reference standard data (liver fibrosis stage evaluated from biopsy or surgical specimens obtained within 6 months of the MR examinations) were available were assigned to the training (534 patients) or the test (100 patients) group. For the training group (54, 53, 81, 113, and 233 patients with fibrosis stages F0, F1, F2, F3, and F4, respectively; mean patient age, 67.4 ± 9.7 years; 388 men and 146 women), MR images with three different section levels were augmented 90-fold (rotated, parallel-shifted, brightness-changed and contrast-changed images were generated; a total of 144 180 images). Supervised training was performed by using the DCNN model to minimize the difference between the output data (fibrosis score obtained through deep learning [FDL score]) and liver fibrosis stage. The performance of the DCNN model was evaluated in the test group (10, 10, 15, 20, and 45 patients with fibrosis stages F0, F1, F2, F3, and F4, respectively; mean patient age, 66.8 years ± 10.7; 71 male patients and 29 female patients) with receiver operating characteristic (ROC) analyses. Results The FDL score was correlated significantly with fibrosis stage (Spearman rank correlation coefficient: 0.63; P < .001). Fibrosis stages F4, F3, and F2 were diagnosed with areas under the ROC curve of 0.84, 0.84, and 0.85, respectively. Conclusion The DCNN model exhibited a high diagnostic performance in the staging of liver fibrosis. © RSNA, 2017 Online supplemental material is available for this article.

Imaging features of subcentimeter hypointense nodules on gadoxetic acid-enhanced hepatobiliary phase MR imaging that progress to hypervascular hepatocellular carcinoma in patients with chronic liver disease.

With the advent of 3-T magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI), many subcentimeter hepatic nodules have been frequently detected in patients with chronic liver disease, and the prediction of subcentimeter nodules that progress to hypervascular hepatocellular carcinoma (HCC) is important. To reveal the imaging features of subcentimeter hypointense nodules on gadoxetic acid-enhanced hepatobiliary phase MR images in patients with chronic liver disease that may be related with progression to hypervascular HCC. This study included 109 patients with 135 subcentimeter hypointense nodules (103 hepatocellular carcinomas [HCCs] and 32 benign nodules) on gadoxetic acid-enhanced hepatobiliary phase. For each subcentimeter nodule, the following imaging features were analyzed: (i) hyperintensity on T2-weighted (T2W) image or DWI; (ii) arterial hypervascularization; and (iii) hypointensity on a portal or late phase. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of those imaging features for predicting subcentimeter nodules that progressed to hypervascular HCC were evaluated. Volume doubling time (VDT) of subcentimeter nodules that progressed to hypervascular HCC was compared to that of growing benign nodules. Arterial hypervascularization with washout yielded the highest specificity (90.6%) and PPV (95.4%) for prediction of subcentimeter nodules that progressed to hypervascular HCC. Combining hyperintensity on T2W image or DWI and arterial hypervascularization with washout did not raise the specificity (90.6%) for prediction of subcentimeter nodules that progressed to hypervascular HCC. Mean VDT (112.2 ± 106.3 days) of subcentimeter nodules that progressed to hypervascular HCC during follow-up was significantly shorter than those of benign subcentimeter nodules (1258 ± 766.5 days, P < 0.001). Arterial hypervascularization with washout in subcentimeter hypointense nodules on gadoxetic acid-enhanced hepatobiliary phase in patients with chronic liver disease is strongly related with progression to hypervascular HCC.

Appearance of hepatocellular carcinoma on gadoxetic acid-enhanced hepato-biliary phase MR imaging: a systematic review.

To perform a systematic review of the contrast behaviour of HCC on Gd-EOB-DTPA hepato-biliary phase MRI. This review was completed in accordance with the recommendations outlined in the preferred reporting items for systematic reviews statement. In all reports, qualitative analysis of signal intensity (SI) of HCC on hepato-biliary phase was performed: the relative SI of HCC. When available, a quantitative analysis of tumour enhancement was evaluated. A total of 106 studies were retrieved, of which 41 met the inclusion criteria. The total number of patients was 2550, with 3132 HCC. MRI showed 3110 HCC (22 non-detected). 2692/3110 (87 %) HCC were hypointense on Gd-EOB-DTPA-enhanced hepatocyte-phase MRI, 134 (4 %) isointense; 106 (3 %) hyperintense and 178 (6 %) iso-hyperintense. In 26 articles, 1653 HCCs were classified as follows: 519 well-differentiated, 883 moderately differentiated, 251 poorly differentiated. Among well-differentiated HCC, 445 (86 %) were hypointense, 12 isointense (2 %), 9 hyperintense (2 %), 53 iso/hyperintense (10 %). Among moderately differentiated HCC, 774 (88 %) were hypointense, 8 isointense (1 %), 27 hyperintense (3 %), 74 iso/hyperintense (8 %). Among poorly differentiated HCCs, 245 (98 %) were hypointense, one isointense, one hyperintense and four iso-hyperintense (2 %). We found a Chi-square (χ (2)) equivalent to 25,082 (p < 0.001). The percentage of lesions iso/hyper/iso-hyper is the same when considering well-differentiated and moderately differentiated HCC; when considering poorly differentiated HCC, the percentage of lesions iso/hyper/iso-hyper is significantly lower. Conversely, the percentage of lesions hypointense is significantly more represented in poorly differentiated HCC compared to well-differentiated and moderately differentiated HCC.

Diagnostic Per-Patient Accuracy of an Abbreviated Hepatobiliary Phase Gadoxetic Acid–Enhanced MRI for Hepatocellular Carcinoma Surveillance

OBJECTIVE. The purpose of this study is to evaluate the per-patient diagnostic performance of an abbreviated gadoxetic acid-enhanced MRI protocol for hepatocellular carcinoma (HCC) surveillance. MATERIALS AND METHODS. A retrospective review identified 298 consecutive patients at risk for HCC enrolled in a gadoxetic acid-enhanced MRI-based HCC surveillance program. For each patient, the first gadoxetic acid-enhanced MRI was analyzed. To simulate an abbreviated protocol, two readers independently read two image sets per patient: set 1 consisted of T1-weighted 20-minute hepatobiliary phase and T2-weighted single-shot fast spin-echo (SSFSE) images; set 2 included diffusion-weighted imaging (DWI) and images from set 1. Image sets were scored as positive or negative according to the presence of at least one nodule 10 mm or larger that met the predetermined criteria. Agreement was assessed using Cohen kappa statistics. A composite reference standard was used to determine the diagnostic performance of each image set for each reader. RESULTS. Interreader agreement was substantial for both image sets (κ = 0.72 for both) and intrareader agreement was excellent (κ = 0.97-0.99). Reader performance for image set 1 was sensitivity of 85.7% for reader A and 79.6% for reader B, specificity of 91.2% for reader A and 95.2% for reader B, and negative predictive value of 97.0% for reader A and 96.0% for reader B. Reader performance for image set 2 was nearly identical, with only one of 298 examinations scored differently on image set 2 compared with set 1. CONCLUSION. An abbreviated MRI protocol consisting of T2-weighted SSFSE and gadoxetic acid-enhanced hepatobiliary phase has high negative predictive value and may be an acceptable method for HCC surveillance. The inclusion of a DWI sequence did not significantly alter the diagnostic performance of the abbreviated protocol.

Incidence for progression of hypervascular HCC in hypovascular hepatic nodules showing hyperintensity on gadoxetic acid-enhanced hepatobiliary phase in patients with chronic liver diseases.

The purpose of this study was to elucidate the incidence and risk factors for the progression of hyperintense nodules, observed in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI), to hypervascular hepatocellular carcinoma (HCC). Hypovascular nodules (n = 157) showing hyperintensity in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were examined in 41 patients. All patients underwent computed tomography (CT) during hepatic arteriography and CT during arterial portography within one month of Gd-EOB-DTPA-enhanced MRI. The incidence of progression to hypervascular or classical HCC was calculated using the Kaplan-Meier method. Tumor size was determined by univariate and multivariate analysis to be an important risk factor of hypervascularization (p = 0.041, odds ratio 1.135). The cumulative incidences of hypervascularization in hypovascular nodules showing hyperintensity on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were 2.4, 4.5, and 6.2 % at 12, 24, and 36 months, respectively. The incidence of hypervascularization was significantly increased in nodules >10 mm in diameter (p = 0.00035). In patients with chronic liver disease, hypovascular nodules presenting as hyperintense in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI and >10 mm in diameter have malignant potential for progression to hypervascular HCC and require careful management.

MR Characterization of Focal Nodular Hyperplasia: Gadoxetic Acid versus Superparamagnetic Iron Oxide Imaging

We evaluated the diagnostic efficacy of gadoxetic acid- and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging for focal nodular hyperplasia (FNH). We retrospectively evaluated 11 patients with 11 FNHs. Both gadoxetic acid- and SPIO-enhanced MR imaging were performed. A 3-dimensional (3D) volumetric interpolated breath-hold examination was used with the gadoxetic acid dynamic study. SPIO-enhanced MR imaging included T₂- and T₂*-weighted images. We quantitatively and qualitatively compared lesion-specific enhancement of both contrast media. The mean signal-to-noise (S/N) ratio of the FNH lesions differed significantly on pre- and postenhanced imaging of each contrast medium (P<0.05); mean contrast-to-noise (C/N) ratio did not (P>0.05). All observers described all lesions as hyperintense in the arterial phase on gadoxetic acid-enhanced MR imaging and observed the presence of central scar, fibrous septa, and rim most clearly in gadoxetic acid-enhanced hepatobiliary phase images. Gadoxetic acid-enhanced MR imaging was more useful than SPIO-enhanced MR imaging in characterizing FNH.

Gadoxetic Acid–Enhanced Hepatobiliary Phase MRI and High-b-Value Diffusion-Weighted Imaging to Distinguish Well-Differentiated Hepatocellular Carcinomas From Benign Nodules in Patients With Chronic Liver Disease

The purpose of this article is to evaluate the value of gadoxetic acid-enhanced hepatobiliary phase imaging and high-b-value diffusion-weighted imaging (DWI) for distinguishing well-differentiated hepatocellular carcinomas (HCCs) from benign hepatocellular nodules in patients with chronic liver disease using 3-T MRI. Forty-five patients with 46 well-differentiated HCCs (mean, 2.3 cm) and 21 patients with 24 benign hepatocellular nodules (five large regenerative nodules and 19 dysplastic nodules; mean, 1.8 cm) were included in this study. Diagnosis of well-differentiated HCCs and benign hepatocellular nodules was made histopathologically by percutaneous biopsy (n = 12 and n = 11, respectively) or surgical resection (n = 34 and n = 13, respectively). Gadoxetic acid-enhanced MRI was performed for all patients, and DWI (b values of 0 and 800 s/mm(2)) was performed for 31 well-differentiated HCCs and 11 benign hepatocellular nodules. Two radiologists performed a consensus review of the MRI scans for signal intensity compared with that of the surrounding liver parenchyma on hepatobiliary phase images and DWI (b value, 800 s/mm(2)) for qualitative analysis. The contrast-to-noise ratio (CNR) and relative contrast enhancement of lesions on hepatobiliary phase images and the apparent diffusion coefficient (ADC) values were assessed for quantitative analysis. In the qualitative analysis, 39 well-differentiated HCCs (85%) and 14 benign hepatocellular nodules (58%) were hypointense on hepatobiliary phase images, and seven well-differentiated HCCs (15%) and 10 benign hepatocellular nodules (42%) were iso- or hyperintense (p = 0.04). Twenty-five well-differentiated HCCs (81%) and three benign hepatocellular nodules (27%) were hyperintense on DWI, with b value of 800 s/mm(2), and six well-differentiated HCCs (19%) and eight benign hepatocellular nodules (73%) were iso- or hypointense (p = 0.01). When lesion hypointensity on hepatobiliary phase images or hyperintensity on DWI were considered signs of HCC in cirrhotic liver, our results yielded sensitivities of 85% and 81% and specificities of 42% and 73%, respectively. In the quantitative analysis, the mean (± SD) relative contrast enhancement ratio of the well-differentiated HCCs (0.76 ± 2.30) was significantly higher than that of benign hepatocellular nodules (0.25 ± 0.97) (p = 0.02). The lesion-to-liver CNRs and the mean ADC values were not significantly different between the two groups (p > 0.05). Hypointensity on gadoxetic acid-enhanced hepatobiliary phase images and hyperintensity on high-b-value DWI to surrounding liver parenchyma suggest well-differentiated HCCs rather than benign hepatocellular nodules in chronic liver disease.

Hypervascular Hepatocellular Carcinoma 1 cm or Smaller in Patients With Chronic Liver Disease: Characterization With Gadoxetic Acid–Enhanced MRI That Includes Diffusion-Weighted Imaging

The purpose of this study was to determine the finding most predictive for characterizing hypervascular hepatocellular carcinoma (HCC) measuring 1 cm or less at gadoxetic acid-enhanced MRI that includes diffusion-weighted images. In this retrospective study, between May 2008 and June 2009, 66 patients with 108 hypervascular HCCs 1 cm or smaller underwent gadoxetic acid-enhanced 3-T MRI that included diffusion-weighted images. The diagnosis of HCC was determined by surgical resection in 32 cases, percutaneous biopsy in three cases, or interval growth to larger than 1 cm on follow-up images in accordance with the American Association for the Study of Liver Diseases guidelines in 73 cases. MRI findings of HCC and 33 benign hypervascular lesions in a control group were analyzed by two radiologists in consensus. They based their assessments on the presence or absence of the following five findings: hyperintensity on T2-weighted images, hyperintensity on diffusion-weighted images with low b values, washout pattern, capsular enhancement, and hypointensity on gadoxetic acid-enhanced hepatobiliary phase images. The findings were compared by use of univariate and multivariate analyses. No HCC with capsular enhancement was found. Fifty-seven HCCs (52.8%) had four findings, 36 (33.3%) had three, nine (8.3%) had two findings, and six (5.6%) had one finding. Univariate analysis showed significant differences between the HCC and control groups with respect to four findings (p < 0.0001). Multivariate analysis showed that hyperintensity on T2-weighted (p < 0.0001) and diffusion-weighted (p = 0.0081) images were statistically significant MRI findings for predicting HCC. Hyperintensity on both T2- and diffusion-weighted images is helpful in the diagnosis of hypervascular HCC smaller than 1 cm in diameter.

Hepatocellular Carcinoma: Hepatocyte-selective Enhancement at Gadoxetic Acid–enhanced MR Imaging—Correlation with Expression of Sinusoidal and Canalicular Transporters and Bile Accumulation

To investigate the mechanism of enhancement of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced hepatobiliary phase magnetic resonance (MR) images and to characterize HCC thus enhanced. This retrospective study was approved by the institutional review board, and patient informed consent for research use of the resected specimen was obtained. MR images in 25 patients (20 men, five women; mean age, 68 years; range, 49-82 years) with 27 resected hypervascular HCCs (one well, 13 moderately, 13 poorly differentiated) that demonstrated hepatocyte-selective enhancement on gadoxetic acid-enhanced MR images, were quantitatively studied, and findings were correlated with results of immunohistochemical staining for a sinusoidal transporter, organic anion transporting polypeptide (OATP) 1B1 (OATP1B1) and/or OATP1B3 (OATP1B1 and/or -1B3), and a canalicular transporter, multidrug resistance-associated protein 2 (MRP2), and also with bile accumulation in tumors. Statistical analysis was performed with the Student t test and Scheffé post hoc test. Combined with positive OATP1B1 and/or -1B3 expression (O+), two patterns of MRP2 expression contributed to high enhancement: decreased expression (M-, n = 3) and increased expression at the luminal membrane of pseudoglands (M+[P], n = 3). Nodules without OATP1B1 and/or -1B3 expression (O-, n = 13) and nodules with O+ associated with increased MRP2 expression only at the canaliculi (M+[C], n = 8) induced significantly lower enhancement than those with the two expression patterns described before (O+/M- group vs O- group, P = .002; O+/M- group vs O+/M+[C] group, P = .047; O+/M+[P] group vs O- group, P < .001; O+/M+[P] group vs O+/M+[C] group, P < .001). Nodules with bile pigment (n = 12) showed significantly higher enhancement (P = .004); all five nodules (one well differentiated HCC, four moderately differentiated HCCs), which were enhanced more than adjacent liver parenchyma, contained bile pigment. High hepatocyte-selective enhancement is induced by expression patterns of transporters, which may result in accumulation of gadoxetic acid in cytoplasm of tumor cells or in lumina of pseudoglands. An HCC with gadoxetic acid enhancement is characterized by bile accumulation in tumors.