Gadoxetic Acid-enhanced Magnetic Resonance Imaging Research Articles

Indeterminate liver lesions on gadoxetic acid-enhanced magnetic resonance imaging of the liver: Case-based radiologic-pathologic review

Different histopathological manifestations of focal liver lesions show varying common and uncommon imaging findings and some pathologies may show similar appearance despite of different histopathology. It is necessary to characterise focal liver lesions accurately as not only benign and malignant lesions are managed differently, but also certain benign lesions have differing management. These lesions are increasingly being detected due to rapid growth of use of cross-sectional imaging as well as improvement in image quality and new imaging techniques. Contrast enhanced magnetic resonance imaging (MRI) is considered the gold standard technique in characterising focal liver lesions. Addition of gadoxetic acid has been shown to significantly increase diagnostic accuracy in the detection and characterization of liver abnormalities. Classic imaging characteristics of common liver lesions, including their behaviour on gadoxetic acid enhanced MRI, have been described in literature over recent years. It is important to be familiar with the typical aspects of these lesions as well as know the uncommon and overlapping imaging features to reach an accurate diagnosis. In this article, we will review the well-described characteristic imaging findings of common and rare focal liver lesions and present several challenging cases encountered in the clinical setting, namely hepatocellular adenoma, focal nodular hyperplasia, hepatic angiomyolipoma, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours as well as a pleomorphic liposarcoma of the liver.

MRI-Radiomics Prediction for Cytokeratin 19-Positive Hepatocellular Carcinoma: A Multicenter Study.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has poor prognosis. Cytokeratin (CK)19-positive (CK19+) HCC is especially aggressive; early identification of this subtype and timely intervention can potentially improve clinical outcomes. In the present study, we developed a preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI)-based radiomics model for noninvasive and accurate classification of CK19+ HCC. A multicenter and time-independent cohort of 257 patients were retrospectively enrolled (training cohort, n = 143; validation cohort A, n = 75; validation cohort B, n = 39). A total of 968 radiomics features were extracted from preoperative multisequence MR images. The maximum relevance minimum redundancy algorithm was applied for feature selection. Multiple logistic regression, support vector machine, random forest, and artificial neural network (ANN) algorithms were used to construct the radiomics model, and the area under the receiver operating characteristic (AUROC) curve was used to evaluate the diagnostic performance of corresponding classifiers. The incidence of CK19+ HCC was significantly higher in male patients. The ANN-derived combined classifier comprising 12 optimal radiomics features showed the best diagnostic performance, with AUROCs of 0.857, 0.726, and 0.790 in the training cohort and validation cohorts A and B, respectively. The combined model based on multisequence MRI radiomics features can be used for preoperative noninvasive and accurate classification of CK19+ HCC, so that personalized management strategies can be developed.

Characteristics and Lenvatinib Treatment Response of Unresectable Hepatocellular Carcinoma with Iso-High Intensity in the Hepatobiliary Phase of EOB-MRI.

Simple SummaryHCC with alterations in CTNNB1 (which encodes β-catenin) is resistant to immune checkpoint inhibitors and is associated with HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI in resectable HCC. However, the prevalence, characteristics, mutation profile, and treatment response in unresectable HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI are not well clarified. In this study, we showed that the prevalence was 13%, and the response to lenvatinib does not differ between HCC with and without iso-high intensity in the hepatobiliary phase of EOB-MRI. We analyzed CTNNB-1 mutations using cell-free DNA, providing support for their association with iso-high intensity in the hepatobiliary phase of EOB-MRI.In hepatocellular carcinoma (HCC), CTNNB-1 mutations, which cause resistance to immune checkpoint inhibitors, are associated with HCC with iso-high intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in resectable HCC; however, analyses on unresectable HCC are lacking. This study analyzed the prevalence, characteristics, response to lenvatinib, and CTNNB-1 mutation frequency in unresectable HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI. In 52 patients with unresectable HCC treated with lenvatinib, the prevalence of iso-high intensity in the hepatobiliary phase of EOB-MRI was 13%. All patients had multiple HCCs, and 3 patients had multiple HCCs with iso-high intensity in the hepatobiliary phase of EOB-MRI. Lenvatinib response to progression-free survival and overall survival were similar between patients with or without iso-high intensity in the hepatobiliary phase of EOB-MRI. Seven patients (three and four patients who had unresectable HCC with or without iso-high intensity in the hepatobiliary phase of EOB-MRI, respectively) underwent genetic analyses. Among these, two (67%, 2/3) who had HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI carried a CTNNB-1 mutation, while all four patients who had HCC without iso-high intensity in the hepatobiliary phase of EOB-MRI did not carry the CTNNB-1 mutation. This study’s findings have clinical implications for the detection and treatment of HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI.

Transient Severe Motion Artifact on Arterial Phase in Gadoxetic Acid-Enhanced Liver Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

The aims of this study were to determine the incidence of transient severe motion artifact (TSM) on arterial phase gadoxetic acid-enhanced magnetic resonance imaging of the liver and to investigate the causes of heterogeneity in the published literature. Original studies reporting the incidence of TSM were identified in searches of PubMed, Embase, and Cochrane Library databases. The pooled incidence of TSM was calculated using random-effects meta-analysis of single proportions. Subgroup analyses were conducted to explore causes of heterogeneity. A total of 24 studies were finally included (single arterial phase, 19 studies with 3065 subjects; multiple arterial phases, 8 studies with 2274 subjects). Studies using single arterial phase imaging reported individual TSM rates varying from 4.8% to 26.7% and a pooled incidence of TSM of 13.0% (95% confidence interval, 10.3%-16.2%), which showed substantial study heterogeneity. The pooled incidence of TSM in the studies using multiple arterial phase imaging was 3.2% (95% confidence interval, 1.9%-5.2%), which was significantly less than in those studies using single arterial phase imaging (P < 0.001). In the subgroup analysis, the geographical region of studies and the definition of TSM were found to be causes of heterogeneity. The incidence of TSM was higher in studies with Western populations from Europe or North America than in those with Eastern (Asia/Pacific) populations (16.0% vs 8.8%, P = 0.005). Regarding the definition of TSM, the incidence of TSM was higher when a 4-point scale was used for its categorization than when a 5-point scale was used (20.0% vs 11.0%, P = 0.008), and a definition considering motion artifact on phases other than arterial phase imaging lowered the incidence of TSM compared with it being defined only on arterial phase imaging (11.3% vs 20.3%, P = 0.018). The incidence of TSM on arterial phase images varied across studies and was associated with the geographical region of studies and the definition of TSM. Careful interpretation of results reporting TSM might therefore be needed.

Preoperative Prediction of Cytokeratin 19 Expression for Hepatocellular Carcinoma with Deep Learning Radiomics Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging.

PurposeCytokeratin 19 (CK19) expression is a proven independent prognostic predictor of hepatocellular carcinoma (HCC). This study aimed to develop and validate the performance of a deep learning radiomics (DLR) model for CK19 identification in HCC based on preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI).Patients and MethodsA total of 141 surgically confirmed HCCs with preoperative gadoxetic acid-enhanced MRI from two institutions were included. Prediction models were established based on hepatobiliary phase (HBP) images using a training set (n=102) and validated using time-independent (n=19) and external (n=20) test sets. A receiver operating characteristic curve was used to evaluate the performance for CK19 prediction. Recurrence-free survival (RFS) was also analyzed by incorporating the CK19 expression and other factors.ResultsFor predicting CK19 expression, the area under the curve (AUC) of the DLR model was 0.820 (95% confidence interval [CI]: 0.732–0.907, P<0.001) with sensitivity, specificity, accuracy of 0.800, 0.766, and 0.775, respectively, and reached 0.781 in the external test set. Combined with alpha fetoprotein, the AUC increased to 0.833 (95% CI: 0.753–0.912, P<0.001) and the sensitivity was 0.960. Intratumoral hemorrhage and peritumoral hypointensity on HBP were independent risk factors for HCC recurrence by multivariate analysis. Based on predicted CK19 expression and the independent risk factors, a nomogram was developed to predict RFS and achieved C-index of 0.707.ConclusionThis study successfully established and verified an optimal DLR model for preoperative prediction of CK19-positive HCCs based on gadoxetic acid-enhanced MRI. The prediction of CK19 expression in HCC using a non-invasive method can help inform preoperative planning.

Prediction of microvascular invasion via gadoxetic acid-enhanced MRI in hepatocellular carcinoma: The implication of planning extent of the hepatectomy

The purpose of this study was to identify predictive factors for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) using clinical factors and imaging findings of magnetic resonance imaging (MRI), to divide the patients into a subgroup with similar prognosis and finally to evaluate whether the extent of hepatectomy can affect long-term outcomes in the subgroup. A total of 410 patients with surgically resected single HCC (≤ 5 cm) who underwent preoperative gadoxetic acid-enhanced MRI were included. Significant predictive factors for MVI were identified via univariate and multivariate analysis and used to divide the patients into low and high-risk groups. In the subgroup, long-term outcomes were analyzed after the minor versus major hepatectomy. Four variables were independently associated with MVI: alpha-fetoprotein ≥ 400 ng/mL (p = 0.021), tumor size ≥ 3 cm (p < 0.001), non-smooth tumor margin (p < 0.001) and arterial peritumoral enhancement (p = 0.001). Patients with a combination of three or more factors were classified as the high-risk group (n = 103), which showed worse prognosis than the low-risk group (n = 307) (p < 0.001). While the extent of hepatectomy was not associated with prognosis in the low-risk group, major hepatectomy significantly improved disease-free survival (p < 0.011) and decreased early intrahepatic recurrence (< 2 years) (p = 0.005) than minor hepatectomy in the high-risk patients. The patients who had a combination of three or more predictive factors for MVI showed worse prognosis after hepatectomy for HCC and major hepatectomy improved long-term outcomes in these high-risk patients.

Non-contrast Magnetic Resonance Imaging versus the Multiphase Computed Tomography with Respect to the Asia-Pacific Clinical Practice Guidelines: A Diagnostic Performance Study for Liver Cancer.

Guidelines recommend multiphasic computed tomography (CT) and/or contrast-enhanced magnetic resonance imaging (MRI) for the detection of hepatocellular carcinoma. The objectives of the study were to compare diagnostic parameters of non-contrast MRI against multiphase CT for diagnostic of hepatocellular carcinoma in patients who at risk of liver cancer considering Asia-Pacific clinical practice guidelines as the reference standard. Medical records of patients with chronic hepatic disease or have suspected liver cancer in surveillance of fewer than 100 days and underwent multiphasic CT, gadoxetic acid-enhanced MRI, and liver biopsy for diagnosis of liver cancer were included in analysis. Enhancement during the arterial phase and wash-out during a delayed phase or portal-venous considered as hepatocellular carcinoma in the multiphase CT. Mild-to-moderate hypersensitivity in imaging, presence of fat on out-of-phase imaging, non-enhancing capsule(s), mosaic appearance, hemorrhagic content, and/or nodule-in-nodule considered as hepatocellular carcinoma in MRI. Asia- Pacific clinical practice guidelines considered for biopsy/histopathology for detection of hepatocellular carcinoma. For detection of hepatocellular carcinoma, non-contrast MRI had higher sensitivity (0.843 vs. 0.762, P < .001, q = 3.919) and accuracy (0.755 vs. 0.571, P < .001, q = 3.362) than the multiphase CT. While specificity was the same (0.864 vs. 0.809, P < .001, q = 2.584). Non-contrast MRI had 0-0.91 diagnostic confidence and multiphase CT had 0.49-0.81 diagnostic confidence for the detection of hepatocellular carcinoma. Non-contrast MRI easily facilitates the decision of chemotherapy and/or radiotherapy than multiphase CT in hepatocellular carcinoma.

Quantitative assessment of liver function with hepatocyte fraction: Comparison with T1 relaxation‐based indices

PurposeThis study aimed to assess the use of hepatocyte fraction in gadoxetic acid-enhanced magnetic resonance imaging (MRI) for quantitatively evaluating the liver function in comparison with T1 relaxation‐based indices. MethodsThis retrospective study included 79 patients with chronic liver disease, who were divided into 2 groups based on the results of the indocyanine green retention test (ICG). All patients underwent a gadoxetic acid-enhanced MRI of the liver. Pre- and post-contrast Look-Locker sequences were used 20 min after gadoxetic acid administration to acquire T1 mapping. Two readers independently identified and measured the MRI parameters [five T1 relaxation‐based indices (T1pre, T1post, rrT1, R1post/R1pre and ΔR1) and two hepatocyte fraction indices (HeF and KHep)]. An Independent-samples t test was used to compare each parameter for the two groups. Pearson correlation analysis was used to analyze the correction in each parameter and 15-minute ICG retention rate (ICG-R15). Receiver operating characteristic analyses were performed to differentiate the diagnostic performance of each parameter in ICG-R15 ≤ 20 % and ICG-R15 > 20 % groups. ResultsT1pre and T1post were significantly lower in the ICG-R15 ≤ 20 % group than in the ICG-R15 > 20 % group (P < 0.05). rrT1, R1post/R1pre, ΔR1, HeF, and KHep were significantly higher in the ICG-R15 ≤ 20 % group than in the ICG-R15 > 20 % group (P < 0.05). The correction coefficients between T1pre, T1post, rrT1, R1post/R1pre, ΔR1, HeF, KHep, and ICG-R15 were 0.343, 0.783, –0.833, –0.781, –0.803, –0.819, and –0.832, respectively. The area under the curves (AUCs) of T1pre, T1post, rrT1, R1post/R1pre, ΔR1, HeF, and KHep in assessing the ICG-R15＞20 % groups were 0.761, 0.945, 0.912, 0.912, 0.948, 0.945, and 0.950, respectively. KHep had the highest AUC, sensitivity, and specificity. ConclusionHepatocyte fraction based on gadoxetic acid-enhanced T1-mapping MRI is an efficient diagnostic tool for the quantitative evaluation of liver function.

Prediction of Microvascular Invasion in Hepatocellular Carcinoma via Deep Learning: A Multi-Center and Prospective Validation Study.

Simple SummaryMicrovascular invasion (MVI) is an independent risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). Preoperative knowledge of MVI would assist with tailored surgical strategy making to prolong patient survival. Previous radiological studies proved the role of noninvasive medical imaging in MVI prediction. However, hitherto, deep learning methods remained unexplored for this clinical task. As an end-to-end self-learning strategy, deep learning may not only achieve improved prediction accuracy, but may also visualize high-risk areas of invasion by generating attention maps. In this multicenter study, we developed deep learning models to perform MVI preoperative assessments using two imaging modalities—computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). A head-to-head prospective validation was conducted to verify the validity of deep learning models and achieve a comparison between CT and EOB-MRI for MVI assessment. The findings put forward a better understanding of MVI preoperative prediction in HCC management.Microvascular invasion (MVI) is a critical risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). Preknowledge of MVI would assist tailored surgery planning in HCC management. In this multicenter study, we aimed to explore the validity of deep learning (DL) in MVI prediction using two imaging modalities—contrast-enhanced computed tomography (CE-CT) and gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). A total of 750 HCCs were enrolled from five Chinese tertiary hospitals. Retrospective CE-CT (n = 306, collected between March, 2013 and July, 2019) and EOB-MRI (n = 329, collected between March, 2012 and March, 2019) data were used to train two DL models, respectively. Prospective external validation (n = 115, collected between July, 2015 and February, 2018) was performed to assess the developed models. Furthermore, DL-based attention maps were utilized to visualize high-risk MVI regions. Our findings revealed that the EOB-MRI-based DL model achieved superior prediction outcome to the CE-CT-based DL model (area under receiver operating characteristics curve (AUC): 0.812 vs. 0.736, p = 0.038; sensitivity: 70.4% vs. 57.4%, p = 0.015; specificity: 80.3% vs. 86.9%, p = 0.052). DL attention maps could visualize peritumoral high-risk areas with genuine histopathologic confirmation. Both DL models could stratify high and low-risk groups regarding progression free survival and overall survival (p < 0.05). Thus, DL can be an efficient tool for MVI prediction, and EOB-MRI was proven to be the modality with advantage for MVI assessment than CE-CT.

Hepatobiliary phase images of gadoxetic acid-enhanced MRI may improve accuracy of predicting the size of hepatocellular carcinoma at pathology.

Gadoxetic acid-enhanced magnetic resonance imaging (MRI) has been widely used in clinical practice. However, scientific evidence is lacking for recommending a particular sequence for measuring tumor size. To retrospectively compare the size of hepatocellular carcinoma (HCC) measured on different gadoxetic acid-enhanced MRI sequences using pathology as a reference. A total of 217 patients with single HCC who underwent gadoxetic acid-enhanced MRI before surgery were included. The size of the HCC was measured by two abdominal radiologists independently on the following sequences: T1-weighted; T2-weighted; b-500 diffusion-weighted imaging (DWI); and arterial, portal venous, transitional, and hepatobiliary phases. Tumor size measured on MRI was compared with pathological size by using Pearson correlation coefficient, independent-sample t test, and Bland-Altman plot. Agreement between two readers was evaluated with intraclass correlation coefficient (ICC). Correlation between the MR images and pathology was high for both readers (0.899-0.955). Absolute error between MRI and pathologic assessment was lowest on hepatobiliary phase images for both readers (reader 1, 2.8±4.2 mm; reader 2, 3.2±3.4 mm) and highest on arterial phase images for reader 1 (4.9±4.4 mm) and DWI phase images for reader 2 (5.1±4.9 mm). Absolute errors were significantly different for hepatobiliary phase compared with other sequences for both readers (reader 1, P≤0.012; reader 2, P≤0.037). Inter-reader agreements for all sequence measurements were strong (0.971-0.997). The performance of gadoxetic acid-enhanced MRI sequences varied with HCC size, and the hepatobiliary phase may be optimal among these sequences.

Considerable effects of imaging sequences, feature extraction, feature selection, and classifiers on radiomics-based prediction of microvascular invasion in hepatocellular carcinoma using magnetic resonance imaging.

Microvascular invasion (MVI) has a significant effect on the prognosis of hepatocellular carcinoma (HCC), but its preoperative identification is challenging. Radiomics features extracted from medical images, such as magnetic resonance (MR) images, can be used to predict MVI. In this study, we explored the effects of different imaging sequences, feature extraction and selection methods, and classifiers on the performance of HCC MVI predictive models. After screening against the inclusion criteria, 69 patients with HCC and preoperative gadoxetic acid-enhanced MR images were enrolled. In total, 167 features were extracted from the MR images of each sequence for each patient. Experiments were designed to investigate the effects of imaging sequence, number of gray levels (Ng), quantization algorithm, feature selection method, and classifiers on the performance of radiomics biomarkers in the prediction of HCC MVI. We trained and tested these models using leave-one-out cross-validation (LOOCV). The radiomics model based on the images of the hepatobiliary phase (HBP) had better predictive performance than those based on the arterial phase (AP), portal venous phase (PVP), and pre-enhanced T1-weighted images [area under the receiver operating characteristic (ROC) curve (AUC) =0.792 vs. 0.641/0.634/0.620, P=0.041/0.021/0.010, respectively]. Compared with the equal-probability and Lloyd-Max algorithms, the radiomics features obtained using the Uniform quantization algorithm had a better performance (AUC =0.643/0.666 vs. 0.792, P=0.002/0.003, respectively). Among the values of 8, 16, 32, 64, and 128, the best predictive performance was achieved when the Ng was 64 (AUC =0.792 vs. 0.584/0.697/0.677/0.734, P<0.001/P=0.039/0.001/0.137, respectively). We used a two-stage feature selection method which combined the least absolute shrinkage and selection operator (LASSO) and recursive feature elimination (RFE) gradient boosting decision tree (GBDT), which achieved better stability than and outperformed LASSO, minimum redundancy maximum relevance (mRMR), and support vector machine (SVM)-RFE (stability =0.967 vs. 0.837/0.623/0.390, respectively; AUC =0.850 vs. 0.792/0.713/0.699, P=0.142/0.007/0.003, respectively). The model based on the radiomics features of HBP images using the GBDT classifier showed a better performance for the preoperative prediction of MVI compared with logistic regression (LR), SVM, and random forest (RF) classifiers (AUC =0.895 vs. 0.850/0.834/0.884, P=0.558/0.229/0.058, respectively). With the optimal combination of these factors, we established the best model, which had an AUC of 0.895, accuracy of 87.0%, specificity of 82.5%, and sensitivity of 93.1%. Imaging sequences, feature extraction and selection methods, and classifiers can have a considerable effect on the predictive performance of radiomics models for HCC MVI.

Differentiating Liver Hemangioma from Metastatic Tumor Using T2-enhanced Spin-echo Imaging with a Time-reversed Gradient-echo Sequence in the Hepatobiliary Phase of Gadoxetic Acid-enhanced MR Imaging.

Purpose: To evaluate the utility of T2-enhanced spin-echo imaging using the time-reversed gradient echo sequence (T2FFE imaging) in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI (Gd-EOB-MRI) for differentiating hemangiomas from metastatic tumors.Methods: A total of 61 patients with 133 liver lesions, including 37 hemangiomas and 96 metastatic tumors, were scanned by Gd-EOB-MRI. Four data sets were independently analyzed by two readers: (1) 3D fat-suppressed T2-weighted imaging (FS-T2WI) alone; (2) the combination of 3D FS-T2WI and T2FFE imaging in the HBP of Gd-EOB-MRI; (3) the combination of 3D FS-T2WI, diffusion-weighted imaging (DWI) with the b-value of 1000 s/mm2 and the apparent diffusion coefficient (ADC); and (4) a dynamic study of Gd-EOB-MRI. After classifying the lesion sizes as ≤ 10 mm or > 10 mm, we conducted a receiver-operating characteristic analysis to compare diagnostic accuracies among the four data sets for differentiating hemangiomas from metastatic tumors.Results: The areas under the curves (AUCs) of the four data sets of two readers were: (1) ≤ 10 mm (0.85 and 0.91) and > 10 mm (0.88 and 0.97), (2) ≤ 10 mm (0.94 and 0.94) and > 10 mm (0.96 and 0.95), (3) ≤ 10 mm (0.90 and 0.87) and > 10 mm (0.89 and 0.95), and (4) ≤ 10 mm (0.62 and 0.67) and > 10 mm (0.76 and 0.71), respectively. Data sets (2) and (3) showed no significant differences in AUCs, but both showed significantly higher AUCs compared to that of (4) regardless of the lesion size (P < 0.05).Conclusion: The combination of 3D FS-T2WI and T2FFE imaging in the HBP of Gd-EOB-MRI achieved an accuracy equivalent to that of the combination of 3D FS-T2WI, DWI, and ADC and might be helpful in differentiating hemangiomas from metastatic tumors.

Risk of nephrogenic systemic fibrosis in patients with impaired renal function undergoing fixed-dose gadoxetic acid-enhanced magnetic resonance imaging.

To assess the risk of nephrogenic systemic fibrosis (NSF) in patients with renal impairment undergoing gadoxetic acid-enhanced magnetic resonance imaging. This retrospective study included patients who had an estimated glomerular filtration rate (eGFR) below 60mL/min per 1.73m2 or had undergone dialysis around the time of gadoxetic acid exposure from January 2010 to November 2019. All patients received at least one intravenous injection of gadoxetic acid at a fixed dose of 2.5mmol. The primary endpoint was the development of NSF after exposure to gadoxetic acid based on Girardi's clinicopathological scoring system. A total of 204 patients with renal impairment received 424 injections of gadoxetic acid, of which 131 and 54 had an eGFR of 30-59 and < 30mL/min per 1.73m2, respectively, and 19 had undergone hemodialysis. Eighty-two patients received multiple injections, with 23 receiving five or more injections. The dose of each exposure ranged from 0.02 to 0.07mmol/kg and the cumulative doses ranged from 0.02 to 0.45mmol/kg. Thirty-three patients had concomitant Child-Pugh class B or C cirrhosis. No NSF was detected during follow-up (median 20months; range 6days to 111months). The upper bound of the 95% confidence interval for NSF risk was 2.2% and 1.1% per patient and examination, respectively. No NSF was detected in this study. However, it is premature to ascertain the risk of NSF using gadoxetic acid in patients with renal impairment and further studies are warranted.

A subcentimeter duodenal neuroendocrine neoplasm with a liver metastasis upgraded to G3: a case report

BackgroundAlthough duodenal neuroendocrine neoplasms (DuNENs) usually have indolent phenotypes, some DuNENs exhibit aggressive clinical manifestations. Tumor size > 1 cm, lymph node metastasis, and high grade have been associated with poor prognosis. However, preoperative risk evaluation is often difficult, because Ki-67 index on biopsy is frequently underestimated due to the intratumor heterogeneity. Here, we present a case of a subcentimeter DuNEN with a low Ki-67 index on endoscopic biopsy, who developed lymph node metastasis and high-grade liver metastasis.Case presentationThe patient was a 52-year-old female who presented an epigastric pain. Esophagogastroduodenoscopy revealed a duodenal submucosal lesion with a size of 8 mm. The endoscopic biopsy showed DuNEN with a Ki-67 index of 3.3% (G2 categorized by the World Health Organization 2019 classification). We performed an open partial duodenectomy with adjacent lymph node dissection. Pathological examination of the resected specimens revealed a Ki-67 index of 13.5% (G2) in the “hot spot” and lymph node metastasis. A hepatic low-density area detected on preoperative contrast-enhanced computed tomography appeared to be a liver metastasis on postoperative gadoxetic acid-enhanced magnetic resonance imaging. Subsequently, we performed a laparoscopic partial hepatectomy. Pathological examination of the liver specimen showed a metastatic neuroendocrine tumor with a Ki-67 index of 27.5% (NET-G3). The patient has been alive for 14 months since the hepatectomy.ConclusionsThis case shows the possibility of high malignant potential of DuNEN even if the primary lesion is < 1 cm and has a low Ki-67 index on biopsy.

Quantitative analysis of gadoxetic acid-enhanced MRI for the differential diagnosis of focal liver lesions: Comparison between estimated intralesional gadoxetic acid retention by T1 mapping and conventional processing methods

PurposeTo compare the estimated quantity of intratumor gadoxetic acid retention using T1 mapping of gadoxetic acid-enhanced magnetic resonance imaging (MRI) versus conventional processing methods for the differential diagnosis of focal liver lesions. MethodsSeventy patients with hepatic lesions (colorectal metastasis (CRM) [n = 28], hepatocellular carcinoma (HCC) [n = 20], hemangioma [n = 12], and intrahepatic cholangiocarcinoma (ICC) [n = 10]) underwent gadoxetic acid-enhanced MRI, including pre- and post-contrast T1-weighted imaging and T1 mapping. Quantitative analyses included the lesion-to-liver signal intensity ratio (SIR) on hepatobiliary phase images, the pre- and post-contrast lesion T1 value difference (ΔT1 [ms]), and the lesion retention index (LRI [%]), which was the estimated intralesional gadoxetic acid retention calculated on pre- and post-contrast T1 maps using a two-compartment pharmacokinetic model. Results were compared between the four subcategories of focal liver lesions using the Kruskal-Wallis test, followed by the post-hoc Dunn’s test and receiver operating characteristic (ROC) analysis to distinguish between pairs of the four lesion subcategories. ResultsThis study identified significant differences in the LRI of the four lesion subcategories (p < 0.01), without significant differences in ΔT1 or SIR. Post-hoc analysis demonstrated significant differences in CRM vs. hemangioma (p < 0.01), hemangioma vs. ICC (p < 0.01), and HCC vs. ICC (p = 0.047) for the LRI. ConclusionsThe quantity of intratumor gadoxetic acid retention estimated using pre- and post- contrast T1 mapping could distinguish focal liver lesions, unlike conventional processing methods, and captured unique lesion characteristics.

Current role of intraoperative ultrasonography in hepatectomy.

Hepatectomy had a high mortality rate in the previous decade because of inadequate techniques, intraoperative blood loss, liver function reserve misdiagnoses, and accompanying postoperative complications. However, the development of several modalities, including intraoperative ultrasonography (IOUS), has made hepatectomy safer. IOUS can provide real-time information regarding the tumor position and vascular anatomy of the portal and hepatic veins. Systematic subsegmentectomy, which leads to improved patient outcomes, can be performed by IOUS in open and laparoscopic hepatectomy. Although three-dimensional (3D) computed tomography and gadoxetic acid-enhanced magnetic resonance imaging have been widely used, IOUS and contrast-enhanced IOUS are important modalities for risk analyses and making decisions regarding resectability and operative procedures because of the vital anatomical information provided and high sensitivity for liver tumors, including "disappearing" liver metastases. Intraoperative color Doppler ultrasonography can be used to delineate the vascular anatomy and evaluate the blood flow volume and velocity in hepatectomy patients and recipients of deceased- and living-donor liver transplantation after vessel reconstruction and liver positioning. For liver surgeons, IOUS is an essential technique to perform highly curative hepatectomy safely, although recent advances have also been made in virtual modalities, such as real-time virtual sonography with 3D visualization.

A Case of Focal Hepatic Sinusoidal Obstruction Mimicking Colorectal Liver Metastases

Introduction: Oxaliplatin is a platinum-based antineoplastic agent, and it is common for the treatment of colorectal cancer. Oxaliplatin-induced hepatic sinusoidal obstruction syndrome (HSOS) has been reported, and it may present as reticular hypointensity on hepatobiliary phase images of gadoxetic acid-enhanced magnetic resonance images (EOB-MRI). We experienced that HSOS presented focal lesions, and we could not distinguished between HSOS and metastatic lesion in the liver. Method: A case report. Result: A 51-year old female underwent high anterior resection for rectal cancer, and the pathological diagnosis was advanced rectal cancer, pT4aN2aM0 pStageIIIc. The patient received six cycles of oxaliplatin-based chemotherapy with capecitabine as postoperative adjuvant chemotherapy. Eight months after the operation, the contrast enhanced computed tomography revealed two low density lesions in the liver. The hepatobiliary phase of the EOB-MRI demonstrated three lesions in the liver as hypointense tumors relative to the surrounding hepatic parenchyma. These findings of the preoperative images were compatible to metastatic liver tumors from the rectal cancer, and we performed limited resection of the liver. Histopathological findings of three lesions which were recognized preoperatively revealed that sinusoid within lobules dilated and space of Disse bled. It indicated sinusoidal obstruction injury. There was no malignant lesion. The patient recovered completely and discharged from our hospital on 7th postoperative day. Conclusions: Focal HSOS mimicking metastatic liver tumors is very rare, and it is difficult to discriminate between focal HSOS and liver metastases in the patients who undergo oxaliplatin-based chemotherapy.

Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma.

PurposeExpression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation.Materials and MethodsTumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed.ResultsWe examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with high-grade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004).ConclusionOur findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acid-enhanced MRI in moderately differentiated HCC.

Prognosis after Curative Resection of Single Hepatocellular Carcinoma with A Focus on LI-RADS Targetoid Appearance on Preoperative Gadoxetic Acid-Enhanced MRI.

ObjectiveTo evaluate the prognostic implications of preoperative magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) with a focus on those with targetoid appearance based on the Liver Imaging Reporting and Data System (LI-RADS), as well as known microvascular invasion (MVI) features.Materials and MethodsThis retrospective study included 242 patients (190 male; mean age, 57.1 years) who underwent surgical resection of a single HCC (≤ 5 cm) as well as preoperative gadoxetic acid-enhanced MRI between January 2012 and March 2015. LI-RADS category was assigned, and the LR-M category was further classified into two groups according to rim arterial-phase hyperenhancement (APHE). The imaging features associated with MVI were also assessed. The overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated.ResultsAmong the 242 HCCs, 190 (78.5%), 25 (10.3%), and 27 (11.2%) were classified as LR-4/5, LR-M with rim APHE, and LR-M without rim APHE, respectively. LR-M with rim APHE (vs. LR-4/5; hazard ratio [HR] for OS, 5.48 [p = 0.002]; HR for RFS, 2.09 [p = 0.042]) and tumor size (per cm increase; HR for OS, 6.04 [p = 0.009]; HR for RFS, 1.77 [p = 0.014]) but not MVI imaging features (p > 0.05) were independent factors associated with OS and RFS. Compared to the 5-year OS and RFS rates in the LR-4/5 group (93.9% and 66.8%, respectively), the LR-M with rim APHE group had significantly lower rates (68.0% and 45.8%, respectively, both p < 0.05), while the LR-M without rim APHE group did not significantly differ in the survival rates (91.3% and 80.2%, respectively, both p > 0.05).ConclusionFurther classification of LR-M according to the presence of rim APHE may help predict the postoperative prognosis of patients with a single HCC.

Does Hepatic Steatosis Influence the Detection Rate of Metastases in the Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI?

The aim of this exploratory study was to evaluate the influence of hepatic steatosis on the detection rate of metastases in gadoxetic acid-enhanced liver magnetic resonance imaging (MRI). A total of 50 patients who underwent gadoxetic acid-enhanced MRI (unenhanced T1w in- and opposed-phase, T2w fat sat, unenhanced 3D-T1w fat sat and 3-phase dynamic contrast-enhanced (uDP), 3D-T1w fat sat hepatobiliary phase (HP)) were retrospectively included. Two blinded observers (O1/O2) independently assessed the images to determine the detection rate in uDP and HP. The hepatic signal fat fraction (HSFF) was determined as the relative signal intensity reduction in liver parenchyma from in- to opposed-phase images. A total of 451 liver metastases were detected (O1/O2, n = 447/411). O1/O2 detected 10.9%/9.3% of lesions exclusively in uDP and 20.2%/15.5% exclusively in HP. Lesions detected exclusively in uDP were significantly associated with a larger HSFF (area under curve (AUC) of receiver operating characteristic (ROC) analysis, 0.93; p < 0.001; cutoff, 41.5%). The exclusively HP-positive lesions were significantly associated with a smaller diameter (ROC-AUC, 0.82; p < 0.001; cutoff, 5 mm) and a smaller HSFF (ROC-AUC, 0.61; p < 0.001; cutoff, 13.3%). Gadoxetic acid imaging has the advantage of detecting small occult metastatic liver lesions in the HP. However, using non-optimized standard fat-saturated 3D-T1w protocols, severe steatosis (HSFF > 30%) is a potential pitfall for the detection of metastases in HP.