Dynamic CT and Gadoxetic Acid-enhanced MRI Characteristics of P53-mutated Hepatocellular Carcinoma.

Background Imaging markers of hepatocellular carcinoma (HCC) on the basis of molecular classification are important for predicting malignancy grade and prognosis. P53-mutated HCC is a major aggressive subtype; however, its imaging characteristics have not been clarified. Purpose To clarify the imaging characteristics of P53-mutated HCC at dynamic CT and gadoxetic acid-enhanced MRI that are correlated with its clinical features, pathologic findings, and prognosis. Materials and Methods In this retrospective single-center study, patients with surgically resected HCC between January 2015 and May 2018 in a university hospital were evaluated. HCC was classified into P53-mutated HCC and non-P53-mutated HCC using immunostaining. Dynamic CT and gadoxetic acid-enhanced MRI findings, clinical features, pathologic findings, and prognosis were compared using Mann-Whitney test, χ2 test, multivariable regression analysis, receiver operating characteristic analysis, Kaplan-Meier method, and log-rank test. Immunohistochemical expression of P53, organic anion transporting polypeptide 1B3 (OATP1B3), and CD34 were evaluated, and the correlations were analyzed using the Pearson correlation test. Results In total, 149 patients (mean age, 67 years ± 9 [SD]; 103 men) with 173 HCCs were evaluated. P53-mutated HCC (n = 28) demonstrated higher serum α-fetoprotein (median, 127.5 ng/mL vs 5.5 ng/mL; P < .001), larger size (40.4 mm ± 29.7 vs 26.4 mm ± 20.5; P = .001), and higher rates of poorly differentiated HCC (22 of 28 [79%] vs 24 of 145 [17%]; P < .001). Dilated vasculature in the arterial phase of dynamic CT (odds ratio, 14; 95% CI: 3, 80; P = .002) and a lower relative enhancement ratio in the hepatobiliary phase (odds ratio, 0.05; 95% CI: 0.01, 0.34; cutoff value, 0.69; P = .002) independently predicted P53-mutated HCC. OATP1B3 expression and P53 expression were inversely correlated (P = .002; R = -0.24). Five-year overall survival was worse for P53-mutated HCC (50.0% vs 72.6%; P = .02). Conclusion Dilated vasculature at the arterial phase of dynamic CT and a lower relative enhancement ratio at the hepatobiliary phase of gadoxetic acid-enhanced MRI were useful markers for P53-mutated hepatocellular carcinoma with poor prognosis. © RSNA, 2022 Online supplemental material is available for this article.

Universal Liver Imaging Lexicon: Imaging Atlas for Research and Clinical Practice.

The use of standardized terms in assessing and reporting disease processes has well-established benefits, such as clear communication between radiologists and other health care providers, improved diagnostic accuracy and reproducibility, and the enhancement and facilitation of research. Recently, the Liver Imaging Reporting and Data System (LI-RADS) Steering Committee released a universal liver imaging lexicon. The current version of the lexicon includes 81 vetted and precisely defined terms that are relevant to acquisition of images using all major liver imaging modalities and contrast agents, as well as lesion- and organ-level features. Most terms in the lexicon are applicable to all patients undergoing imaging of the liver, and only a minority of the terms are strictly intended to be used for patients with high risk factors for hepatocellular carcinoma. This pictorial atlas familiarizes readers with the liver imaging lexicon and includes discussion of general concepts, providing sample definitions, schematics, and clinical examples for a subset of the terms in the liver imaging lexicon. The authors discuss general, technical, and imaging feature terms used commonly in liver imaging, with the goal of illustrating their use for clinical and research applications. Work of the U.S. Government published under an exclusive license with the RSNA. Online supplemental material is available for this article.

Radiation dose considerations in digital radiography with an anti-scatter grid: A study using adult and pediatric phantoms.

BACKGROUND: When using an anti-scatter grid, a decrease in receptor dose caused by its X-ray absorption seems to lead to the misperception that radiation dose needs to be increased even in digital radiography (DR). OBJECTIVE: To demonstrate that there is no need to increase radiation dose in DR with a grid, based on a visual evaluation using an adult and a pediatric abdomen phantom (PAD and PPD , respectively). MATERIALS AND METHODS: Phantom images with and without a grid were obtained with exposure parameters determined based on a preliminarily measured signal-to-noise ratio improvement factor (SIF), an index for potential dose reduction when using a grid. In visual evaluation, four radiologists compared phantom images with a grid applied at different dose reduction rates (0% [no reduction], 18%, 36%, and 59% for PAD and 0% and 11% for PPD ) against an image without a grid at the baseline dose (as the reference). They graded the overall image quality of the former relative to that of the latter (reference) on a 3-point scale (3 = better, 2 = almost equal, 1 = worse). RESULTS: The mean scores for dose reduction rates of 0%, 18%, 36%, and 59% were 3.00, 3.00, 2.75, and 1.00, respectively, for PAD ; those for 0% and 11% were 2.13 and 1.63, respectively, for PPD . These results support the validity of our view that no dose increase is necessary when using an anti-scatter grid. Actually, there is even a potential for improvement in image quality with dose reduction rates of ≤36% for PAD . CONCLUSION: It is worth reconsidering the necessity of increasing radiation dose in the DR imaging of the adult and pediatric abdomens with an anti-scatter grid.

Serum Laminin γ2 Monomer as a Diagnostic and Predictive Biomarker for Hepatocellular Carcinoma.

BACKGROUNDS AND AIMS: Structural dynamics of basement membrane components are still to be elucidated in the process of hepatocarcinogenesis. We evaluated the characteristics of HCC expressing laminin γ2 monomer (LG2m), a basement membrane component not detected in normal tissues, for HCC diagnosis. We further determined whether elevated serum LG2m is a risk factor for HCC development in patients with chronic hepatitis C (CHC). APPROACH AND RESULTS: In HCC cell lines, LG2m was expressed in alpha-fetoprotein (AFP)-negative, CD90-positive cells characterized by highly metastatic natures. Using 14 cell lines and 258 HCC microarray data, we identified that LG2m gene signature was associated with Hoshida's S1/Boyault's G3 molecular subclasses with poor prognosis, which could not be recognized by AFP. Serum LG2m was assessed in 24 healthy donors, 133 chronic liver disease patients, and 142 HCC patients, and sensitivity and specificity of LG2m testing for HCC diagnosis were 62.9% and 70.5%, respectively (cutoff, 30 pg/mL). We evaluated the consequence of LG2m elevation in two independent HCC cohorts (n = 47 and n = 81), and LG2m-high HCC showed poor prognosis with later development of distant organ metastasis (cutoff, 60 pg/mL). LG2m was slightly elevated in a subset of CHC patients, and Kaplan-Meier analysis indicated a high incidence of HCC (n = 70). For validation, we enrolled 399 CHC patients with sustained virological response (SVR) as a multicenter, prospective study, and serum LG2m elevation correlated with a high incidence of HCC in the CHC patients with SVR (P < 0.0001). CONCLUSIONS: LG2m is a predictive biomarker for the development of metastatic HCC. Elevated serum LG2m is an HCC risk in CHC patients who have achieved SVR.

Transcatheter arterial embolization of iatrogenic massive arterioportal fistula in the liver.

BACKGROUND: Massive arterioportal fistula (APF) is naturally irreversible and can induce portal hypertension and portal vein thrombosis (PVT), worsening survival outcomes. PURPOSE: To evaluate the clinical course and details of transarterial embolization (TAE) procedures for massive APF. MATERIAL AND METHODS: This retrospective single-center observational study evaluated the time until embolization after puncture, imaging, embolization methods, and laboratory data of 10 consecutive patients who were diagnosed with massive APF after puncture and underwent TAE at our hospital from 1 April 2012 to 30 September 2019. RESULTS: Out of 10 cases, eight demonstrated a simple type and the other two cases a complex network type on the digital subtraction angiography pattern of massive APF. In two simple-type cases for which re-embolization was required, other subsegmental branches were embolized. The two cases showing a complex network type had been embolized via not only the subsegmental branch, but also the extrahepatic and multiple subsegmental branches. Child-Pugh scores were improved in eight of the ten cases. PVT was seen in six cases before embolization, but disappeared after embolization in all cases, despite the fact that three cases had not received anticoagulant therapy. Six cases had digestive varices before embolization, suggesting portal hypertension, and two of the six cases with esophageal varices and one with gastric varices decreased after embolization. CONCLUSION: TAE for massive APF contributed to the improvement of hepatic reserve, the disappearance of PVT, and the improvement of portal hypertension; however, embolization of multiple branches may still be required in some cases.

Ultrasonography of IgG4-related dacryoadenitis and sialadenitis: Imaging features and clinical usefulness.

OBJECTIVES: To clarify the ultrasonographic features of immunoglobulin G4 (IgG4)-related dacryoadenitis and sialadenitis (IgG4-DS) and their usefulness in clinical diagnostic sessions. METHODS: By re-evaluating 96 consecutive patients with IgG4-related disease, we identified 54 patients (male:female = 37:17; median age, 69.5 years) who underwent lacrimal or submandibular gland (LG or SG, respectively) ultrasonography and computed tomography (CT). Their clinical and ultrasonographic features were retrospectively analysed. Radio-pathological correlations were also examined in LG (23 cases) and SG lesions (20 cases). Additionally, the diagnostic accuracy of CT for LG/SG lesions was evaluated. RESULTS: Abnormal ultrasonographic findings were detected in 33 (LGs) and 38 (SGs) patients, and most of them were observed bilaterally. All lesions were well demarcated and demonstrated diffuse low-echoic areas (rocky pattern) or multiple low-echoic nodules surrounded by high-echoic linear shadows (cobblestone pattern) corresponding to intra-lobular inflammation and inter-lobular fibrosis. Moreover, 42% (LGs; 14/33) and 42% (SGs; 16/38) patients had glandular lesions without clinical symptoms associated with the affected glands. The diagnostic accuracy of CT was ∼80% for LG and 55% for SG. CONCLUSIONS: Ultrasonographic findings in IgG4-DS included diffuse or nodular low-echoic areas with linear high-echoic structures corresponding to inflamed lobules and inter-lobular fibrosis. These findings can help detect IgG4-DS.

Pathologic, Molecular, and Prognostic Radiologic Features of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy with variable biologic aggressiveness based on the tumor grade, presence or absence of vascular invasion, and pathologic and molecular classification. Knowledge and understanding of the prognostic implications of different pathologic and molecular phenotypes of HCC are emerging, with therapeutics that promise to provide improved outcomes in what otherwise remains a lethal cancer. Imaging has a central role in diagnosis of HCC. However, to date, the imaging algorithms do not incorporate prognostic features or subclassification of HCC according to its biologic aggressiveness. Emerging data suggest that some imaging features and further radiologic, pathologic, or radiologic-molecular phenotypes may allow prediction of the prognosis of patients with HCC. An invited commentary by Bashir is available online. Online supplemental material is available for this article. ©RSNA, 2021.

Gadoxetic acid-enhanced MR imaging for hepatocellular carcinoma: molecular and genetic background.

Gadoxetic acid-enhanced magnetic resonance imaging (MRI) plays important roles in diagnosis of hepatic lesions because of its superiority in the detectability of small lesions, its differentiation ability, and its utility for the early diagnosis of hepatocellular carcinoma (HCC). In HCC, expression of organic anion transporting polypeptide (OATP) 1B3 correlates with the enhancement ratio in the hepatobiliary phase. Gadoxetic acid-enhanced MRI, an indirect molecular imaging method, reflects OATP1B3 expression in HCC. OATP1B3 expression gradually decreases from the dysplastic nodule stage to advanced HCC. Decreased expression is a sensitive marker of multistep hepatocarcinogenesis, especially in the early stages. Hypervascular HCCs commonly show hypointensity in the hepatobiliary phase corresponding to a decrease in OATP1B3; however, approximately 10% of HCCs show hyperintensity due to OATP1B3 overexpression. This hyperintense HCC shows less aggressive biological features and has a better prognosis than hypointense HCC. Hyperintense HCC can be classified into a genetic subtype of HCC with a mature hepatocyte-like molecular expression. OATP1B3 expression and the less aggressive nature of hyperintense HCC are regulated by the molecular interaction of ß-catenin signaling and hepatocyte nuclear factor 4α, a tumor suppressor factor. Gadoxetic acid-enhanced MR imaging has the potential to be an imaging biomarker for HCC. KEY POINTS: • The hepatobiliary phase is a sensitive indirect indicator of organic anion transporting polypeptide1B3 (OATP1B3) expression in hepatocellular carcinoma (HCC). • The OATP1B3 expression, namely, enhancement in the hepatobiliary phase, decreases from the very early stage of hepatocarcinogenesis, contributing to early diagnosis of HCC. • HCC showing hyperintensity on the hepatobiliary phase is a peculiar genetic subtype of HCC with OATP1B3 overexpression, a less aggressive nature, and mature hepatocyte-like molecular/genetic features.

Doughnut-like hyperintense nodules on hepatobiliary phase without arterial-phase hyperenhancement in cirrhotic liver: imaging and clinicopathological features.

OBJECTIVES: To determine the imaging and clinicopathological features of MRI doughnut-like nodules (HBP-doughnut nodules), hyperintense at the hepatobiliary phase (HBP) after injection of gadoxetic acid (EOB) and without arterial-phase hyperenhancement (APHE) in cirrhotic liver. METHODS: The Institutional Review Board approved this retrospective study and informed consent was waived. We enrolled 309 consecutive patients with liver cirrhosis who were examined by EOB-MRI, dynamic CT, and angiography-assisted CT between 2008 and 2012 and searched for HBP-doughnut nodules. We evaluated imaging characteristics including haemodynamics and signal intensity of MRI, pathological findings, and frequency of malignant transformation. RESULTS: One hundred and one HBP-doughnut nodules without APHE were identified in 18 patients (6%), including seven of 59 (12%) patients with hepatitis-B-virus-related, nine of 230 (3.9%) with hepatitis-C-virus-related, and two of 33 (6.1%) with alcoholic cirrhosis. All nodules showed enhancement peaks in the portal phase, the same or increased intranodular portal supply on CT during arterial portography, and the same or decreased intranodular arterial supply on CT during hepatic arteriography. On T2-weighted and diffusion-weighted images, 37 (36%) and 24 (24%) nodules, respectively, showed hyperintensity predominantly in the central area. Three nodules were diagnosed by fine needle biopsy as non-neoplastic hepatic nodules. Ninety-three of 101 (92%) nodules in 16 patients were followed up during an observation period of 1163 ± 902 days (range 57-2920 days), and none showed malignant transformation. CONCLUSION: HBP-doughnut nodules without APHE in cirrhotic liver were not infrequent. None became malignant. We propose calling them 'multiacinar cirrhotic nodules' based on the classification by an International Working Party. KEY POINTS: • HBP-doughnut nodules without APHE were seen in 6% of patients with liver cirrhosis. • The enhancement peak of HBP-doughnut nodules without APHE was in the portal phase, which reflected the fact that they were supplied predominantly by the portal vein, based on angiography-assisted CT findings. • None of the HBP-doughnut nodules without APHE in cirrhotic liver became malignant, and in conjunction with limited pathological features, they may be corresponding to multiacinar cirrhotic nodules in the International Working Party classification.

CT imaging comparison between intraductal papillary neoplasms of the bile duct and papillary cholangiocarcinomas.

OBJECTIVES: To identify imaging features that assist in discriminating intraductal papillary neoplasms of the bile duct (IPNBs) from papillary cholangiocarcinomas (PCCs). METHODS: This study was approved by the institutional review board. Using the recently proposed histological diagnostic criteria for biliary papillary neoplasms, IPNBs and PCCs were selected from 537 biliary neoplasms consecutively resected in a 12.5-year period. Clinical and imaging features were compared between the two groups. RESULTS: The histology review identified 19 IPNBs and 48 PCCs, representing an estimated prevalence of IPNBs among biliary neoplasms of 4%. Approximately one half of IPNBs were incidentally found on imaging conducted for other purposes. In terms of tumor location, 15/19 IPNBs (79%) developed in intrahepatic bile ducts, and 41/48 PCCs (85%) in the distal bile duct. Cystic appearance was highly suggestive for IPNBs (p < 0.001). Using these two parameters, 78% of papillary bile duct neoplasms could be classified into IPNBs or PCCs. Other imaging findings favoring IPNBs included frond-like mural nodule, downstream bile duct dilatation, and the lack of abnormal enhancement in the adjacent bile duct. Interestingly, two patients with non-invasive or microinvasive IPNB had undergone abdominal imaging studies > 3 years before, and a retrospective review of the previous images identified small nodular or cystic lesions, suggesting a less progressive nature of IPNBs than currently thought. CONCLUSIONS: Imaging findings useful for discriminating IPNBs from PCCs appear to be tumor location, shape of tumor, appearance of mural nodules, duct dilatation at unaffected duct, and abnormal enhancement of the adjacent bile duct. KEY POINTS: • Intrahepatic location and cystic dilatation of the affected bile duct are the strong discriminators between IPNBs and PCCs. • The shape of the mural nodule and appearance of the neighboring bile duct are helpful for distinguishing IPNBs and PCCs. • The less aggressive behavior of IPNBs compared with PCCs may facilitate less invasive management in patients with IPNB.

CT Findings of Thoracic Paravertebral Lesions in IgG4-Related Disease.

OBJECTIVE. The objective of our study was to characterize the CT findings of IgG4-related paravertebral lesions. MATERIALS AND METHODS. We selected cases of IgG4-related paravertebral lesions that satisfied two inclusion criteria: first, lesions in patients with IgG4-related disease diagnosed by a multidisciplinary approach between April 2007 and June 2018; and, second, patients who had soft-tissue lesions in paravertebral regions on CT images. We added one case of an IgG4-related paravertebral lesion diagnosed pathologically in 2003. Finally, the study consisted of 30 patients (25 men and five women; median age, 69.5 years). We retrospectively evaluated the CT findings of the paravertebral lesions. RESULTS. A total of 31 paravertebral lesions were identified in 30 patients. All lesions were located around thoracic vertebrae, particularly the lower thoracic regions (n = 30). Twenty-six lesions (84%) involved two or more vertebrae in a row. The right side of vertebrae was predominantly affected in all cases except one (30/31 lesions). Radiologically, the paravertebral lesions were characterized as a bandlike, demarcated soft-tissue mass (mean maximum thickness, 8.7 mm) with homogeneous enhancement on late phase images of contrast-enhanced CT. All patients had IgG4-related lesions at other sites. Histologically, paravertebral lesions showed sclerosing inflammation consisting of diffuse lymphoplasmacytic infiltrations with many IgG4-positive plasma cells and irregular fibrosis. CONCLUSION. IgG4-related paravertebral lesions occur mainly in the right side of the lower thoracic vertebrae and present as a homogeneously enhanced bandlike mass corresponding to plasma cell-rich sclerosing inflammation.

Differentiation Between Hepatocellular Carcinoma Showing Hyperintensity on the Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI and Focal Nodular Hyperplasia by CT and MRI.

OBJECTIVE: The purpose of this study is to identify points useful in the imaging differentiation of hepatocellular carcinoma (HCC) showing hyperintensity on the hepatobiliary phase of gadoxetic acid-enhanced MRI and focal nodular hyperplasia (FNH) and FNH-like nodules. MATERIALS AND METHODS: We enrolled consecutive 51 pathologically diagnosed HCCs that were hyperintense on hepatobiliary phase imaging (47 patients, including 44 with cirrhosis) and 10 FNHs and eight FNH-like nodules (16 patients, including five with cirrhosis). Imaging findings of dynamic CT and gadoxetic acid-enhanced MRI were assessed by two radiologists and compared between HCC and FNH. RESULTS: The apparent diffusion coefficient (ADC) was lower in hyperintense HCC than in FNH (p = 0.004). The enhancement patterns of hyperintense HCC and FNH at dynamic CT were significantly different (p < 0.0001), with 95.9% of HCCs and 22.2% of FNHs showing arterial phase enhancement with a washout pattern, and 4.1% of HCCs and 77.8% of FNHs showing arterial phase enhancement without a washout pattern. The frequency of coronalike enhancement was 84.3% in hyperintense HCCs versus 11.1% in FNHs (p < 0.0001). The signal distribution on the hepatobiliary phase was significantly different between hyperintense HCCs and FNHs (p = 0.0002). The frequency of a capsulelike rim was 88.2% versus 22.2%, that of a mosaic appearance was 72.5% versus 11.1%, and that of a central scar was 0% versus 55.6% in hyperintense HCCs versus FNHs (all p < 0.0001). Multivariate logistic regression analysis showed that ADC ratio (p = 0.03; odds ratio, 0.12) and enhancement pattern at dynamic CT (p = 0.04; odds ratio, 16.21) were the independent factors for differentiation between hyperintense HCC and FNH. CONCLUSION: For the diagnosis of hyperintense HCC differentiated from FNH and FNH-like nodule, arterial phase enhancement and washout pattern at dynamic CT and decrease of ADC ratio would be important findings.

Gadoxetic acid-enhanced magnetic resonance imaging reflects co-activation of ß-catenin and hepatocyte nuclear factor 4α in hepatocellular carcinoma.

AIM: The aim of this study is to clarify the correlation of the co-activation of ß-catenin and hepatocyte nuclear factor (HNF)4α with the findings of gadoxetic acid-enhanced magnetic resonance imaging (MRI), organic anion transporting polypeptide (OATP)1B3 expression, and histological findings in hepatocellular carcinoma (HCC). METHODS: One hundred and ninety-six HCCs surgically resected from 174 patients were enrolled in this study. The HCCs were classified into four groups by immunohistochemical expression of ß-catenin, glutamine synthetase (GS), and HNF4α: (i) ß-catenin/GS (positive [+]) HNF4α (+); (ii) ß-catenin/GS (+) HNF4α (negative [-]); (iii) ß-catenin/GS (-) HNF4α (+); and (iv) ß-catenin/GS (-) HNF4α (-). We compared the four groups in terms of the enhancement ratio on the hepatobiliary phase of gadoxetic acid-enhanced MRI, immunohistochemical organic anion transporter polypeptide (OATP)1B3 (a main uptake transporter of gadoxetic acid) expression and histological features, overall survival, and no recurrence survival. The Kruskal-Wallis test, Steel-Dwass multiple comparisons test, Fisher's exact test, and log-rank (Mantel-Cox) test were used for statistical analyses. RESULTS: Enhancement ratio on gadoxetic acid-enhanced MRI in HCC with ß-catenin/GS (+) HNF4α (+) was significantly higher than those of the other three groups (P < 0.001). The OATP1B3 grade was also significantly higher in HCC with ß-catenin/GS (+) HNF4α (+) (P < 0.001). Hepatocellular carcinoma with ß-catenin/GS (+) HNF4α (+) showed the highest differentiation grade as compared to the other groups (P < 0.004). There were no significant differences in portal vein invasion, macroscopic growth pattern, or prognosis analyses between the four groups. CONCLUSION: Co-activation of ß-catenin and HNF4α would promote OATP1B3 expression, and consequently higher enhancement ratio on gadoxetic acid-enhanced MRI and higher differentiation grade in HCC.

Biochemical and Clinical Predictive Approach and Time Point Analysis of Hepatobiliary Phase Liver Enhancement on Gd-EOB-DTPA-enhanced MR Images: A Multicenter Study.

Purpose To identify biochemical factors associated with liver enhancement over time on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) images and predict the optimal time point of the hepatobiliary phase in various clinical settings. Materials and Methods This study was approved by the institutional review boards, and written informed consent was obtained from the 1903 patients enrolled. Simple and multiple logistic regression analyses were performed to investigate the biochemical factors associated with liver-to-spleen contrast (LSC) of at least 1.5 in the hepatobiliary phase. Changes in LSC and lesion-to-liver contrast (LLC) of lesions over time (at 5, 10, 15, and 20 minutes) were investigated with a linear mixed-effects model in patients and lesions. For LSC, the optimal cutoff value was determined with receiver operating characteristic analysis of the most significant variable. Differences in LSC and LLC were analyzed in various clinical settings. Results Ultimately, 1870 patients were evaluated, as 33 were excluded according to study criteria. Prothrombin (PT) activity, total bilirubin level (P = .020), and total cholesterol level (P = .005) were significantly associated with LSC of at least 1.5 at 20 minutes, and PT activity was identified as the most significant factor (odds ratio, 1.271; 95% confidence interval: 1.109, 1.455; P = .001). LSC of at least 1.5 at 20 minutes with PT activity of at least 86.9% and less than 86.9% occurred in 555 of 626 patients (88.6%) and 388 of 575 patients (67.5%), respectively. Satisfactory liver enhancement at 20 minutes was significantly more likely to be achieved by patients with hepatitis B virus than by those with hepatitis C virus (P < .001) and by patients with metastasis than by those with hepatocellular carcinoma (P < .001). No significant difference in LLC was observed in patients examined at 1.5 and 3.0 T (P = .133). Conclusion Hepatic enhancement is significantly associated with PT activity, total bilirubin level, and total cholesterol level. PT activity of at least 86.9% could be used to shorten examination times at Gd-EOB-DTPA-enhanced MR imaging. © RSNA, 2016 Online supplemental material is available for this article.

Benign Hepatocellular Nodules: Hepatobiliary Phase of Gadoxetic Acid-enhanced MR Imaging Based on Molecular Background.

Gadoxetic acid is a contrast agent for magnetic resonance (MR) imaging with hepatocyte-specific properties and is becoming increasingly important in detection and characterization of hepatocellular carcinoma and benign hepatocellular nodules, including focal nodular hyperplasia (FNH), nodular regenerative hyperplasia (NRH), hepatocellular adenoma (HCA), and dysplastic nodule. In these hepatocellular nodules, a positive correlation between the grade of membranous uptake transporter organic anion-transporting polypeptide (OATP) 1B3 expression and signal intensity in the hepatobiliary (HB) phase has been verified. In addition, it has been clarified that OATP1B3 expression is regulated by activation of ß-catenin and/or hepatocyte nuclear factor 4α. On the other hand, recent studies have also revealed some of the background molecular mechanisms of benign hepatocellular nodules. FNH commonly shows iso- or hyperintensity in the HB phase with equal or stronger OATP1B3 expression, with map-like distribution of glutamine synthetase (a target of Wnt/ß-catenin signaling) and OATP1B3 expression. NRH shows doughnut-like enhancement with hypointensity in the central portion in the HB phase with OATP1B3 expression. The majority of HCAs show hypointensity in the HB phase, but ß-catenin-activated HCA exclusively demonstrates iso- or hyperintensity with increased expression of nuclear ß-catenin, glutamine synthetase, and OATP1B3. Dysplastic nodule commonly shows iso- or hyperintensity in the HB phase with similar to increased OATP1B3 expression, but one-third of high-grade dysplastic nodules can be demonstrated as a hypointense nodule with decreased OATP1B3 expression. Knowledge of these background molecular mechanisms of gadoxetic acid-enhanced MR imaging is important not only for precise imaging diagnosis but also understanding of the pathogenesis of benign hepatocellular nodules. ©RSNA, 2016.

Hepatocellular Carcinoma with ß-Catenin Mutation: Imaging and Pathologic Characteristics.

PURPOSE: To identify the imaging features of hepatocellular carcinoma (HCC) associated with ß-catenin mutation and their relationship to pathologic findings. MATERIALS AND METHODS: Institutional ethics committee approval and informed consent were obtained. One hundred thirty-eight surgically resected HCCs were analyzed in this study. Immunohistochemical expression of ß-catenin and its transcriptional product, glutamine synthetase (GS), were graded and classified into three groups: the ß-catenin positive and GS positive group (HCC with ß-catenin mutation), the ß-catenin negative and GS positive group (intermediate HCC), and the ß-catenin negative and GS negative group (HCC without ß-catenin mutation). Clinical, pathologic, and imaging findings from dynamic computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance (MR) imaging (T1-weighted, T2-weighted, diffusion-weighted, and hepatobiliary phase imaging) were evaluated. Correlations among immunohistochemical expression of ß-catenin, GS, and organic anion transporting polypeptide 1B3 (uptake transporter of gadoxetic acid) were evaluated. The χ(2), Kruskal-Wallis, and Spearman correlation tests were used. RESULTS: HCCs with ß-catenin mutation (n = 27) showed a lower median contrast-to-noise ratio at diffusion-weighted imaging than did intermediate HCCs (n = 23) and HCCs without ß-catenin mutation (n = 84) (13.2, 24.4, and 27.0, respectively; P = .02), higher apparent diffusion coefficient (1.33, 1.13, and 1.12, respectively; P < .0001), higher contrast-to-noise ratio (0.58, -28.7, and -45.0, respectively; P < .0001) and higher enhancement ratio during the hepatobiliary phase (0.90, 0.50, and 0.42, respectively; P < .0001). At pathologic examination, HCCs with ß-catenin mutation showed pseudoglandular proliferation and bile production with a higher grade of differentiation (P = .04, .001, and .005, respectively). There were significant positive correlations among expression of ß-catenin, GS, and organic anion transporting polypeptide 1B3 (P < .0001). CONCLUSION: HCCs with ß-catenin mutation showed a higher grade of differentiation with frequent pseudoglandular patterns and bile production, and characteristic imaging findings included a high enhancement ratio at gadoxetic acid-enhanced MR imaging and a high apparent diffusion coefficient at diffusion-weighted imaging. Online supplemental material is available for this article.

Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.

UNLABELLED: The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in ∼15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n=70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n=109). CONCLUSION: This noninvasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease.

Correlation between Gd-EOB-DTPA-enhanced MR imaging findings and OATP1B3 expression in chemotherapy-associated sinusoidal obstruction syndrome.

We report a female case of sinusoidal obstruction syndrome (SOS) diagnosed pathologically after chemotherapy (Pmab+m-FOLFOX6) for ascending colon cancer with multiple liver metastases, focusing on the findings of gadoxetic acid-enhanced MRI (EOB-MRI) and the organic anion transporting polypeptide 1B3 (OATP1B3) expression of in the liver. The patient was a 75-year-old female. She had received chemotherapy (Pmab+m-FOLFOX6) as six cycles for preoperative chemotherapy. After the preoperative chemotherapy, tumor sizes of hepatic metastases were reduced and hepatobiliary phase of EOB-MRI clearly depicted diffuse reticular hypointensity in the background liver. On the other hand, dynamic CT and/or other sequences of EOB-MRI did not show definite abnormality in the background liver. After the operation, this patient was pathologically confirmed as SOS demonstrating centrilobular congestion, sinusoidal dilatation, and perisinusoidal fibrosis. In normal liver parenchyma, OATP1B3 (uptake transporter of the EOB-MRI) expression is observed predominantly in centrilobular hepatocytes (zone 3). On the other hand, OATP1B3 expression was remarkably reduced because of the damages in the centrilobular (zone 3) hepatocytes in this SOS case. This indicated that EOB-MRI might be extremely sensitive in diagnosing SOS in its early stage.