Quantitative Assessment of the Hemodynamic Effects of Intra-Arterial Nitroglycerin on Hepatocellular Carcinoma using Two-Dimensional Perfusion Angiography.

PURPOSE: To determine the hemodynamic effects of intra-arterial nitroglycerin on hepatocellular carcinoma (HCC) using 2-dimensional (2D) perfusion angiography. MATERIALS AND METHODS: Two-dimensional perfusion angiograms obtained prior to radioembolization from September 2019 to February 2020 were retrospectively reviewed. The inclusion criteria were the presence of Liver Imaging Reporting and Data System-5 tumors and angiographically distinguishable tumor and background liver. The exclusion criteria were previously treated tumors and motion-degraded studies. Thirteen patients with 2D perfusion angiograms obtained before and 2 minutes ± 1 after the administration of intra-arterial nitroglycerin were analyzed. The mean patient age was 72 years ± 9 and 11 of 13 (85%) had cirrhosis. The mean maximum tumor dimension was 4.6 cm ± 2.1. Eight tumors were in the right lobe and 5 were in the left lobe. The tumor and background liver 2D perfusion data were processed and the areas under the time-density curves were calculated. The relative perfusion of HCC to background liver was compared before and after nitroglycerin administration using a 2-tailed paired t-test. RESULTS: The mean rate of contrast administration was 1.4 mL/s ± 0.7 and the mean volume administered was 7.1 mL ± 3.3. The mean nitroglycerin dose was 281 µg ± 69. Ten of 13 patients (77%) demonstrated a relative increase in tumor perfusion. The mean HCC to background liver area under the curve ratio was 1.94 ± 0.76 before and 2.40 ± 0.89 after nitroglycerin administration (P < .05). CONCLUSIONS: Intra-arterial nitroglycerin increases previously untreated HCC perfusion relative to background liver as measured by 2D perfusion angiography, but this effect is variable among patients and should be validated with 3-dimensional imaging techniques.

Assessment of blood flow in the hepatic tumors using non-contrast micro flow imaging: Initial experience.

PURPOSE: To evaluate micro-flow imaging (MFI) in depicting the vascular architecture of hepatocellular carcinoma (HCC) and other focal liver lesions. MATERIALS AND METHODS: A total of 81 hepatic lesions were enrolled in this study. Each patient underwent CDFI, MFI, and CEUS examinations. The blood flow was first graded into three types (grade 1, 2 and 3) based on its richness with Adeler classification method. The differences in the grade of blood flow in liver tumors were compared between CDFI and MFI. With respect to the presented morphology, the blood flow was further classified into five types (Type I, II, III, IV and V). The morphological differences in blood flow shown by MFI between malignant and benign hepatic tumors were then analyzed. RESULTS: For the total 81 lesions, MFI detected 61 lesion cases (75.31%) with blood flow grade 2 and 3, which obviously outperformed CDFI which detected 28 cases (34.57%) of grade 2 and 3 (χ2 = 35.27, P = 0.000). The MFI also showed that the most common blood flow morphology of HCC is Type-III (21/48, 43.75%) while the hepatic hemangioma (HEM) is mostly presented as Type V (5/10, 50%). Moreover, the grade of blood flow in MFI varied with different pathological subtypes of HCC (χ2 = 5.610, P = 0.018). CONCLUSIONS: Compared with traditional CDFI, MFI reveals more blood vessels in liver lesions with clearer view of blood flow distribution. Besides, MFI technology can demonstrate grade of blood flow for various differentiation stages of malignant liver tumors.

Perfusion-CT analysis for assessment of hepatocellular carcinoma lesions: diagnostic value of different perfusion maps.

BACKGROUND: Computed tomography liver perfusion (CTLP) has been improved in recent years, offering a variety of perfusion-parametric maps. A map that better discriminates hepatocellular carcinoma (HCC) is still to be found. PURPOSE: To compare different CTLP maps, regarding their ability to differentiate cirrhotic or non-cirrhotic parenchyma from malignant HCC. MATERIAL AND METHODS: Twenty-six patients (11 cirrhotic) with 50 diagnosed HCC lesions, underwent CTLP on a 128-row dual-energy CT system. Nine different maps were generated. Regions of interest (ROIs) were positioned on non-tumorous parenchyma and on HCCs found on previous magnetic resonance imaging. Perfusion parameters for non-cirrhotic and cirrhotic livers were compared. Receiver operating characteristic (ROC) analysis was employed to evaluate each map's ability to discriminate HCCs from non-tumorous livers. Comparison of ROC curves was performed to evaluate statistical significance of differences in the discriminating efficiency of derived perfusion maps. RESULTS: Perfusion parameters for non-tumorous liver and HCCs recorded in cirrhotic patients did not significantly differ from corresponding values recorded in non-cirrhotic patients ( P > 0.05). The highest power for HCC discrimination was found for the maximum-slope-of-increase (MSI) parametric map, with estimated the area under ROC curve of 0.997. An MSI cut-off criterion of 2.2 HU/s was found to provide 96% sensitivity and 100% specificity. Time to peak, blood flow, and transit time to peak were also found to have high discriminating power. CONCLUSION: Among available CTLP-derived perfusion parameters, MSI was found to provide the highest diagnostic accuracy in discriminating HCCs from non-tumorous parenchyma. Perfusion parameters for non-tumorous livers and HCCs were not found to significantly differ between cirrhotic and non-cirrhotic patients.

[Diagnostic value of computed tomographic perfusion imaging of whole liver for quantitative assessment of blood flow state in liver cancer after transcatheter arterial chemoembolization].

Objective: To investigate the diagnostic value of whole liver CT perfusion imaging in the quantitative evaluation of hemodynamic changes before and after transcatheter arterial chemoembolization (TACE). Methods: Twenty-six patients with hepatocellular carcinoma underwent TACE therapies were recruited. Whole -liver computed tomographic perfusion imaging (CTPI) was performed 2~3 days before TACE and 1 month after TACE. We measured the following perfusion parameters: hepatic arterial perfusion (HAP), portal venous perfusion (PVP), total liver perfusion (TLP), hepatic arterial perfusion index (HAPI), and time-to-peak (TTP).The F-test, t-test and Rank sum test were used for statistical analysis. Results: A total of 34 HCC lesions were detected. According to the deposition of lipiodol after TACE, they were divided into a lipiodol dense group (21) and a lipiodol light group (13). The length of hepatocellular carcinoma lesions after TACE showed a decreasing trend compared with preoperative TACE. The lesions in the lipiodol dense group had smaller lesions than those in the lipiodol light group. The preoperative and postoperative longitudinal diameters were (3.12 ± 0.58) cm vs. (1.93 ± 0.79) cm, (2.98 ± 2.01) cm vs. (2.58 ± 2.00) cm, the differences were statistically significant (t = 15.1, 8.65, P < 0.05). The preoperative HAP and HPI of the lipiodol dense group were the highest, and the peritumoral within 1cm was higher than that of the surrounding liver parenchyma. The PVP, TLP, and TTP were highest in the surrounding of liver parenchyma, and 1 cm higher than the tumor area in the background. The corresponding perfusion parameters were statistically significant (P < 0.05); HAP and HPI were 1 cm higher than the surrounding liver parenchyma. After the operation, PVP, TLP and TTP were lower than the background liver parenchyma, the difference was statistically significant (P < 0.05); HAP and HPI decreased by 1 cm after the operation, and the PVP, TLP, and TTP increased. There was no significant difference after operation in the blood perfusion of background liver parenchyma (P ˃ 0.05). The HAP and HPI decreased, and the PVP and TTP increased in the lipiodol light group after operation (P < 0.05). There was no significant difference between the other two regions (P ˃ 0.05). Conclusion: There was no blood perfusion in the lipiodol deposition area after TACE. The perfusion volume of hepatic artery in the peritumoral 1 cm and lipiodol light group decreased and the portal venous perfusion increased. CTPI can quantitatively evaluate blood perfusion state, which is of great significance for the determination of treatment plans before TACE treatment to assume the postoperative therapeutic effect in liver cancer.

Diagnostic accuracy of contrast-enhanced dynamic CT for small hypervascular hepatocellular carcinoma and assessment of dynamic enhancement patterns: Results of two-year follow-up using cone-beam CT hepatic arteriography.

OBJECTIVE: To evaluate the accuracy of CT for small, hypervascular hepatocellular carcinomas (HCCs) and assess the enhancement patterns on CT. MATERIALS AND METHODS: Ninety-nine patients who underwent cone-beam CT hepatic arteriography (CBCT-HA) during initial chemoembolization for HCC suspected on CT were enrolled in this study. A total of 297 hypervascular HCCs (142 ≥ 1 cm, 155 < 1 cm) were confirmed as HCCs based on two-year follow-up CT and CBCT-HA images. During the two-year follow-up, pre-existing hypervascular foci on CBCT-HA were regarded as HCCs at the initial presentation. Two radiologists categorized HCCs according to the following enhancement patterns on CT: type I, arterial enhancement and washout; type II, arterial enhancement without washout; and type III, no arterial enhancement. Two blinded reviewers rated the possibility of HCC. RESULTS: For the 297 HCCs, the enhancement patterns according to size were as follows: type I ≥1 cm in 114 HCCs; type I <1 cm in 40 HCCs; type II ≥1 cm in 16 HCCs; type II <1 cm in 37 HCCs; type III ≥1 cm in 12 HCCs; and type III <1 cm in 10 HCCs. The remaining 68 HCCs (22.9%) were not detected on CT. The detection rates of HCCs ≥ 1 cm were 83.1%, 76.8%, and 83.1% in the formal report for reviewer 1 and reviewer 2. In comparison, the detection rates of HCCs < 1 cm were 20.6%, 17.4%, and 17.4% in the formal report for reviewer 1 and reviewer 2. CONCLUSION: Many subcentimeter sized hypervascular HCCs were frequently missed or not evident on CT at the initial diagnostic workup. CT has limitations for diagnosing HCCs that are <1 cm in size or have atypical enhancement patterns.

Assessment of Microvascular Invasion of Hepatocellular Carcinoma with Diffusion Kurtosis Imaging.

Purpose To evaluate the potential role of diffusion kurtosis imaging and conventional magnetic resonance (MR) imaging findings including standard monoexponential model of diffusion-weighted imaging and morphologic features for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Materials and Methods Institutional review board approval and written informed consent were obtained. Between September 2015 and November 2016, 84 patients (median age, 54 years; range, 29-79 years) with 92 histopathologically confirmed HCCs (40 MVI-positive lesions and 52 MVI-negative lesions) were analyzed. Preoperative MR imaging examinations including diffusion kurtosis imaging (b values: 0, 200, 500, 1000, 1500, and 2000 sec/mm2) were performed and kurtosis, diffusivity, and apparent diffusion coefficient maps were calculated. Morphologic features of conventional MR images were also evaluated. Univariate and multivariate logistic regression analyses were used to evaluate the relative value of these parameters as potential predictors of MVI. Results Features significantly related to MVI of HCC at univariate analysis were increased mean kurtosis value (P < .001), decreased mean diffusivity value (P = .033) and apparent diffusion coefficient value (P = .011), and presence of infiltrative border with irregular shape (P = .005) and irregular circumferential enhancement (P = .026). At multivariate analysis, mean kurtosis value (odds ratio, 6.25; P = .001), as well as irregular circumferential enhancement (odds ratio, 6.92; P = .046), were independent risk factors for MVI of HCC. The mean kurtosis value for MVI of HCC showed an area under the receiver operating characteristic curve of 0.784 (optimal cutoff value was 0.917). Conclusion Higher mean kurtosis values in combination with irregular circumferential enhancement are potential predictive biomarkers for MVI of HCC. © RSNA, 2017.

Non-Hypervascular Hypointense Nodules at Gadoxetic Acid MRI: Hepatocellular Carcinoma Risk Assessment with Emphasis on the Role of Diffusion-Weighted Imaging.

INTRODUCTION AND AIM: In cirrhotic patients, the characterization of hypovascular nodules, hypointense on hepatobiliary phase gadoxetic acid disodium-enhanced magnetic resonance images (Gd-EOB-DTPA-enhanced MRI), is essential to look for the proper approach strategy. Our objective was to evaluate the imaging features and risk assessment of hypovascular nodules, hypointense on Gd-EOB-DTPA-enhanced MRI, focusing on the diagnostic value of diffusion-weighted imaging (DWI). MATERIAL AND METHODS: This prospective study includes 35 patients with 50 hypovascular hypointense nodules. Signal intensity on T2-weighted images and DWI, vascular pattern on dynamic contrast-enhanced MRI and on hepatobiliary phase, and volume doubling time were analyzed for each nodule as well as patient's clinical features. Univariate and multivariate analyses were made to determine the variables associated with the development of hypervascular pattern. RESULTS: On 24 months follow-up period, 40% of the hypointense nodules (mean size 14 mm ± 6.1) became hypervascular hepatocellular carcinoma (HCC) with 6 and 12 months cumulative risk of 45 and 55%. Nine/12 (75%, mean size 15.50 mm ± 7.2) that appeared hyperintense in DWI at first exam show malignant transformation (p value = 0.007). Univariate and multivariate analyses identified hyperintensity at initial DWI (OR 6.49; 95% CI 1.28-32.80; p value = 0.009) and size ≥10 mm (OR 6.22; 95% CI 1.57-24.63; p value = 0.024) as independent factors with the development of HCC. CONCLUSION: In conclusion, hypovascular lesions ≥10 mm and those hyperintense in DWI were associated with progression to hypervascular HCC. A close follow-up or histological characterization is recommended to improve patients outcome and to develop effective treatment.

Transarterial hepatic chemoembolization with 70-150 µm drug-eluting beads: assessment of clinical safety and liver toxicity profile.

PURPOSE: To assess the incidence and severity of adverse events (AEs) in the form of clinical symptoms and liver/biliary injuries (LBI) in patients with hepatic malignancies treated with transarterial chemoembolization using 70-150 µm drug-eluting beads (DEBs). MATERIALS AND METHODS: A single-institution retrospective analysis was performed in 37 patients (25 patients with hepatocellular carcinoma and 12 patients with metastatic disease) who underwent 43 sessions of segmental/subsegmental 70-150 µm DEB transarterial chemoembolization with doxorubicin (38 sessions) or irinotecan (5 sessions). Patient inclusion criteria included the presence of the following lesion features: small diameter (≤ 3 cm), hypovascular, or with areas of residual disease after other locoregional therapies. Mean tumor diameter was 3.4 cm. Mean imaging and clinical follow-up periods were 171 days and 373 days, respectively. Clinical, laboratory, and imaging data were used to identify and classify clinically symptomatic AEs per session and LBI per patient according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Predictors for the occurrence of LBI were evaluated by logistic regression analysis. RESULTS: No grade 4 or 5 AEs were recorded. Clinically symptomatic AEs occurred in 29 (67.4%) sessions (grade 1-2, 28 sessions; grade 3, 1 session), all constituting postembolization syndrome. Asymptomatic LBI occurred in 11 (29.7%) patients (grade 1, 8 patients; grade 2, 3 patients). The mean time between 70-150 µm DEB transarterial chemoembolization session and appearance of LBI was 71 days (range, 21-223 d). No predictive factors for the development of LBI were identified. CONCLUSIONS: Transarterial chemoembolization with 70-150 µm DEBs was considered safe in the present study population given the acceptably low incidence and severity of AEs.

Transradial arterial chemoembolization reduces complications and costs in patients with hepatocellular carcinoma.

PURPOSE: To improve patient comfort and reduce complications, clinical benefit of a transradial approach for transcatheter arterial chemoembolization (TACE) was evaluated in patients with hepatocellular carcinoma (HCC). METHODS: A total of 284 patients with HCC for TACE was divided into transradial approach group (n = 126) and transfemoral approach group (n = 158). These two groups of cases were retrospectively compared with regard to complications, the procedural time, X-ray exposure time, length of hospitalization, and hospital costs. RESULTS: There were lower incidence rates of complications including abdominal distension (42.85% vs. 87.97%, P> 0.001), vomiting (53.17% vs. 77.22%, P < 0.001), lumbago (1.59% vs. 97.46%, P < 0.001), and dysuria (0% vs. 62.03%, P < 0.001) in the transradial group as compared with the transfemoral group. The time required for catheterization and total X-ray exposure time were less in the transradial group compared with the transfemoral group (Pall < 0.001). The hospital stay time and costs required for catheterization were less in the transradial group compared with the transfemoral group (P < 0.001 and P = 0.001, respectively). In addition, hepatic angiography and TACE were completed in 100% and 99.2% cases in transfemoral and transradial groups, respectively. CONCLUSIONS: Transradial approach for TACE improves quality of life in patients with HCC by offering fewer complications and lower costs compared with transfemoral approach.

Liver computed tomographic perfusion in the assessment of microvascular invasion in patients with small hepatocellular carcinoma.

OBJECTIVES: Detecting microvascular invasion (mVI) in patients with hepatocellular carcinoma is a diagnostic challenge. The present study aimed to acquire a series of quantitative perfusion parameters from liver computed tomography (CT) with a 320-slice scanner in patients with small hepatocellular carcinoma (sHCC) and study its efficacy in identifying mVI. MATERIALS AND METHODS: Fifty-six patients who underwent hepatic resection for sHCC (≤3 cm) were preoperatively examined with a 320-detector row CT scanner. Histopathological analyses of liver biopsies confirmed that 18 patients had sHCC with mVI and that 38 patients had sHCC without mVI. Hepatic artery flow, portal vein flow (PVF), and perfusion index were measured in both tumor and normal liver tissues. Nonparametric receiver operating characteristic curve analysis was performed to quantify the accuracy of the perfusion CT parameters. RESULTS: The tumor PVF (PVFtumor), difference in PVF between tumor and liver tissue (ΔPVF), and the ΔPVF/liver PVF ratio (rPVF) were significantly higher in sHCC with mVI than in sHCC without mVI (P = 0.0094, P = 0.0018, and P = 0.0007, respectively; Wilcoxon signed rank test). The PVFtumor, ΔPVF, and rPVF correctly predicted mVI in 73.2% (sensitivity, 66.7%; specificity, 76.3%; cutoff, 103.8 mL per 100 mL/min), 76.8% (sensitivity, 66.7%; specificity, 81.6%; cutoff, -53.65 mL per 100 mL/min), and 83.9% (sensitivity, 77.8%; specificity, 86.8%; cutoff, -0.38) of a total of 56 patients with sHCC, respectively. Other parameters were not significantly different between the groups. CONCLUSIONS: Liver CT perfusion provides a noninvasive, quantitative method that can predict mVI in patients with sHCC through measurement of 3 perfusion parameters: PVFtumor, ΔPVF, and rPVF.

Assessment of angiogenesis of hepatocellular carcinoma using dynamic contrast enhanced MR and histopathologic correlation in an experimental rat model.

BACKGROUND/AIMS: To assess the perfusion parameters and angiogenesis of HCC using dynamic contrast enhanced(DCE) MR and to correlate it with histopathologic findings in an experimental rat model. METHODOLOGY: Twenty rats were continuously infused with diethylnitrosamine (DEN) for tumor induction. After 32 to 36 weeks of DEN treatment, the rats underwent MRI of the liver with a 3-T MR imaging system. Perfusion parametric maps and perfusion parameters such as, time to peak (TTP) and peak enhancement (PE) were obtained by using a commercially available software package. The nodules were correlated precisely to DCE MR images. RESULTS: A total of 13 nodules were found in 12 rats; 5 dysplastic nodule (DN)s were identified in 5 rats and 8 HCCs (3 Edmonson grade I, 2 Edmonson grade I-II, 3 Edmonson grade II) were found in 7 rats. There were significant differences in mean values of PE and HPH (histogram peak height) of PE between DN and HCC. Mean value and HPH of PE showed statistically significant correlation with tumor grade. CONCLUSIONS: There were significant differences in perfusion parameters between DN and HCC. DCE MR imaging can be used in the differential diagnosis and management of liver disease in hepatocarcinogenesis.

Quantitative assessment of lipiodol deposition after chemoembolization: comparison between cone-beam CT and multidetector CT.

PURPOSE: To evaluate the ability of cone-beam computed tomography (CBCT) performed directly after transarterial chemoembolization to assess ethiodized oil (Lipiodol) deposition in hepatocellular carcinoma (HCC) and compare it with unenhanced multidetector computed tomography (CT). MATERIALS AND METHODS: Conventional transarterial chemoembolization was used to treat 15 patients with HCC, and CBCT was performed to assess Lipiodol deposition directly after transarterial chemoembolization. Unenhanced multidetector CT was performed 24 hours after transarterial chemoembolization. Four patients were excluded because the margin of tumor or area of Lipiodol deposition was unclear. The image enhancement density of the entire tumor and liver parenchyma was measured by ImageJ software, and tumor-to-liver contrast (TLC) was calculated. In addition, volumetric measurement of tumor and Lipiodol was performed by semiautomatic three-dimensional volume segmentation and compared using linear regression to evaluate consistency between the two imaging modalities. RESULTS: The mean value of TLC on CBCT was not significantly different from TLC on multidetector CT (337.7 HU ± 233.5 vs 283.0 HU ± 152.1, P = .103).The average volume of the whole tumor and of only the regions with Lipiodol deposition and the calculated average percentage of Lipiodol retention on CBCT were not significantly different compared with multidetector CT (tumor volume, 9.6 cm(3) ± 11.8 vs 10.8 cm(3) ± 14.2, P = .142; Lipiodol volume, 6.3 cm(3) ± 7.7 vs 7.0 cm(3) ± 8.1, P = .214; percentage of Lipiodol retention, 68.9% ± 24.0% vs 72.2% ± 23.1%, P = .578). Additionally, there was a high correlation in the volume of tumor and Lipiodol between CBCT and multidetector CT (R(2) = 0.919 and 0.903). CONCLUSIONS: The quantitative image enhancement and volume analyses demonstrate that CBCT is similar to multidetector CT in assessing Lipiodol deposition in HCC after transarterial chemoembolization.

Assessment of response to sorafenib in advanced hepatocellular carcinoma using perfusion computed tomography: results of a pilot study.

AIMS: This prospective pilot study investigated the feasibility of perfusion computed tomography parameters as surrogate markers of angiogenesis and early response following sorafenib administration in patients with advanced hepatocellular carcinoma. METHODS: Ten patients were evaluated with perfusion computed tomography before starting sorafenib and after 3 months. Blood flow, blood volume, mean transit time, hepatic arterial fraction, and permeability surface-product were compared in tumour lesions and in hepatic parenchyma at baseline and at follow-up. Correlation between these parameters and changes in alpha-fetoprotein levels was calculated. RESULTS: At baseline, blood volume, blood flow, hepatic arterial fraction and permeability surface values were higher in lesions compared to those in hepatic parenchyma, while mean transit time was lower (p<0.05). After sorafenib treatment, only mean transit time was significantly increased versus baseline (p<0.05). At follow-up, plasma alpha-fetoprotein levels decreased in all patients. At follow-up, an inverse correlation was observed between baseline mean transit time and changes in alpha-fetoprotein (r=-0.6685, p=0.0125), as well as a correlation between baseline blood flow and alpha-fetoprotein (r=0.6476, p=0.0167). CONCLUSION: This pilot study suggests that after sorafenib treatment an increase in mean transit time observed in tumour lesions is inversely correlated with alpha-fetoprotein reductions after therapy. Mean transit time may represent a possible marker of response irrespectively of alpha-fetoprotein values.

Dynamic contrast-enhanced ultrasound (DCE-US) for easy and rapid evaluation of hepatocellular carcinoma compared to dynamic contrast-enhanced computed tomography (DCE-CT)--a pilot study.

PURPOSE: To check the feasibility of the easy quantification of tumor vascularization derived from dynamic contrast-enhanced ultrasound (DCE-US) in comparison to dynamic contrast-enhanced computed tomography (DCE-CT) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 19 patients with cirrhosis and histologically proven HCC prospectively underwent CEUS (SonoVue) and CT (Imeron400). Following CEUS, the software ImageJ was used for the easy quantification of the echogenicity in HCC lesions and tumor-free liver parenchyma. For DCE-CT we used the software Hepacare and created arterial enhancement fraction color maps of the whole liver and HCC lesions. RESULTS: Unifocal/multifocal HCCs were detected in 12/7 (US) and 10/9 patients (CT) and biopsied nodules were defined as a reference lesion with a median of 40 mm (US) and 42 mm (CT). CEUS showed HCC-typical hyper-/hypoenhancement in the arterial/late phase in 16/19 reference lesions, while all reference lesions showed an HCC-typical vascular pattern in CT. With DCE-US, quantitative assessment could not be performed in 3/19 patients due to respiratory motion or insufficient image quality. 13/16 reference lesions showed an HCC-typical vascular pattern. Quantitative assessment was possible with DCE-CT in all patients and all reference nodules showed HCC-typical values of the arterial enhancement fraction. There was no statistical difference between CEUS, DCE-US and DCE-CT in the quantitative assessment of contrast enhancement. CONCLUSION: The quantitative evaluation of DCE-US was feasible in HCC without a statistical difference with respect to DCE-CT. Further studies with a larger study population including small nodules ≤ 2 cm are needed to assess whether this technique is helpful in routine ultrasound.

Transarterial radioembolization versus chemoembolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial.

BACKGROUND: Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization ((90)Y-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a ß-emitting isotope, delivering selective internal radiation to the tumor. (90)Y-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and (90)Y-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma. METHODS/DESIGN: In this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either (90)Y-RE or TACE with drug eluting beads. Patients assigned to (90)Y-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease. Patients assigned to TACE will receive a maximum of three consecutive transarterial treatment sessions. Patients will undergo structural follow-up for a timeframe of two years post treatment. Post procedural magnetic resonance imaging (MRI) will be performed at one and three months post trial entry and at three-monthly intervals thereafter for two years to assess tumor response. Primary outcome will be time to progression. Secondary outcomes will be overall survival, tumor response according to the modified RECIST criteria, toxicities/adverse events, treatment related effect on total liver function, quality of life, treatment-related costs and cost-effectiveness. TRIAL REGISTRATION: NCT01381211.

Hepatocellular nodules in liver cirrhosis: MR evaluation.

Liver cirrhosis is a major public health problem worldwide. Common causes of cirrhosis include hepatitis C virus, hepatitis B virus, alcohol consumption, and nonalcoholic steatohepatitis. Cirrhotic livers are characterized by advanced hepatic fibrosis and the development of hepatocellular nodules such as regenerative nodules, dysplastic or neoplastic nodules. Cirrhosis is the strongest predisposing factor for hepatocellular carcinoma (HCC). For example, viral hepatitis is the main risk factor for cirrhosis and is associated with the increased incidence (1%-4% per year) of HCC after development of cirrhosis. Currently, a variety of imaging modalities, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) are used in noninvasive evaluation of patients with chronic liver disease and suspected HCC. With technological development of MR scanners, MR imaging has emerged as an important imaging modality for assessing cirrhosis and its complications such as HCC. The recent advance in MR is the introduction of faster sequences which have allowed high-quality imaging of the entire liver with high intrinsic soft-tissue contrast, and also multiphasic dynamic MRI that is essential for the detection and characterization of HCC. In addition, functional MRI including diffusion-weighted MRI, MR elastography, and new MR contrast agent with dual function have been investigated for the clinical utility of detection and characterization of HCCs. In this article, we provide an overview of the state-of-the-art MR imaging techniques being used for noninvasive assessment of hepatocellular nodules including conventional dynamic imaging, liver-specific contrast-enhanced MR imaging, diffusion-weighted imaging, MR spectroscopy, and MR elastography.

Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. METHODS: CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. RESULTS: In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor rim was significantly higher than that in the controls. HBF, HBV, HAI, HAP and HPP, but not MTT and PS, were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CONCLUSIONS: CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.

Assessment of hepatocellular carcinoma by contrast-enhanced ultrasound with perfluorobutane microbubbles: comparison with dynamic CT.

OBJECTIVE: The aim of this study was to evaluate tumour vascularity and Kupffer cell imaging in hepatocellular carcinoma (HCC) using contrast-enhanced ultrasonography (CEUS) with Sonazoid (perfluorobutane) and to compare performance with dynamic CT. METHODS: We studied 118 nodules in 88 patients with HCC. HCC was diagnosed as a hyperenhancement lesion in the arterial phase with washout in the portal phase on dynamic CT or by percutaneous biopsy. We observed tumour vascularity at the early vascular phase (10-30 s after contrast injection) and Kupffer imaging at the post-vascular phase (after 10 min). RESULTS: Detection of vascularity at the early vascular phase was 88% in nodules that were found to be hypervascular on dynamic CT and 28% in hypo-/isovascular nodules; the detection of local recurrence nodules was 92%. The detection of vascularity was significantly lower in nodules >9 cm deep than in those ≤9 cm deep, but was not affected by tumour size. The detection of tumours at the post-vascular phase on CEUS was 83% in nodules with low density in the portal phase on dynamic CT and 82% in nodules with isodensity. The rate did not depend on the severity of underlying liver disease; rates decreased in nodules deeper than 9 cm, those smaller than 2 cm in diameter and in iso-enhancing nodules at the early vascular phase of CEUS. CONCLUSION: CEUS with Sonazoid is a useful tool for assessing the vascularity of HCC and is equal to that of dynamic CT; however, the detectability of HCC vascularity is affected by location.

A pictorial review of benign hepatocellular nodular lesions: comprehensive radiological assessment incorporating the concept of anomalous portal tract syndrome.

BACKGROUND/PURPOSE: Although the pathological categorization system advocated by the International Working Party (IWP) on Terminology has been helpful in categorizing benign hepatocellular lesions, the diverse clinicopathological features of the lesions still cause confusion of diagnosis in clinical settings. Recently, an integrated disease concept termed "anomalous portal tract syndrome" (APTS) has been proposed as a congenital anomaly of the portal tract, being a single unifying etiological factor underlying the disorder. In this article, we discuss the radiological features of benign nodular hepatocellular lesions incorporated in the concept of APTS. METHODS: We systematically reviewed the literature on benign hepatocellular lesions based on the concept of APTS, as well as standard IWP terminology. For this pictorial review, we selected six representative cases and assessed the radiological features of the cases based on the concept of APTS. RESULTS: The comprehensive assessment based on APTS enabled the systematic categorization of benign hepatocellular lesions, including nodular regenerative hyperplasia, large regenerative nodules, partial nodular transformation, focal nodular hyperplasia, and hepatocellular adenoma, and was helpful in understanding the overlapping features of these lesions. CONCLUSIONS: Although the disease concept of APTS is still evolving, it is nonetheless helpful in comprehensively understanding the clinicopathological and radiological features of various benign hepatocellular lesions.

Sono-hepatic-arteriography (Sono-HA) in the assessment of hepatocellular carcinoma in patients undergoing transcatheter arterial chemoembolization (TACE).

PURPOSE: The aim of our study was to evaluate sono-hepatic-arteriography in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization. MATERIALS AND METHODS: We evaluated 15 patients with hepatocellular carcinoma undergoing TACE who presented in our institution from February 2006 to May 2008. All patients underwent a conventional B-mode ultrasound examination using a high-end machine and a multi-frequency transducer (2.5 - 4 MHz) before dynamic contrast-enhanced ultrasound examination was carried out. For the sono-hepatic-arteriography 1 ml SonoVue was injected as a bolus using the formerly placed intraarterial catheter. Biphasic enhanced computed tomography was performed using a 16-slice CT scanner up to 48 hours before transcatheter arterial chemoembolization and during follow-up. RESULTS: The lesion size (of the largest lesion) ranged from 1 to 13 centimeters in their largest diameter (mean: 4.8 cm). Contrast-enhanced ultrasound diagnosed more lesions than B-mode sonography in eight cases and more lesions than computed tomography in 5 patients. The findings of sono-hepatic-arteriography were correct in fourteen cases (93.3 %). Direct impact on patient management was seen in eleven patients (73.3 %). CONCLUSION: We were able to show that the application of an intraarterial sonographic contrast agent during embolization is able to diagnose new lesions on the one hand and to assess the embolization success on the other. This might improve transcatheter arterial chemoembolization results and patient outcome.