Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND Non-invasive differential diagnosis between hepatocellular carcinoma(HCC)and other liver cancer(i.e.cholangiocarcinoma or metastasis)is highly challenging and definitive diagnosis still relies on histological exam.The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features.Dynamic contrast-enhanced ultrasound(DCEUS)with standardized software could help to overcome these obstacles,providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion.AIM To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules.METHODS A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS Rise time was significantly higher in HCC patients with a standardized mean difference(SMD)of 0.83(95%CI:0.48-1.18).Similarly,other statistically significant parameters were mean transit time local with a SMD of 0.73(95%CI:0.20-1.27),peak enhancement with a SMD of 0.37(95%CI:0.03-0.70),area wash-in area under the curve with a SMD of 0.47(95%CI:0.13-0.81),wash-out area under the curve with a SMD of 0.55(95%CI:0.21-0.89)and wash-in and wash-out area under the curve with SMD of 0.51(95%CI:0.17-0.85).SMD resulted not significant in fall time and wash-in rate,but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma.CONCLUSION DCEUS could improve non-invasive diagnosis of HCC,leading to less liver biopsy and early treatment.This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

Liver metastases:Contrast-enhanced ultrasound compared with computed tomography and magnetic resonance

The development of ultrasound contrast agents with excellent tolerance and safety profiles has notably improved liver evaluation with ultrasound(US)for several applications,especially for the detection of metastases.In particular,contrast enhanced ultrasonography(CEUS)allows the display of the parenchymal microvasculature,enabling the study and visualization of the enhancement patterns of liver lesions in real time and in a continuous manner in all vascular phases,which is similar to contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging.Clinical studies have reported that the use of a contrast agent enables the visualization of more metastases with significantly improved sensitivity and specificity compared to baseline-US.Furthermore,studies have shown that CEUS yields sensitivities comparable to CT.In this review,we describe the state of the art of CEUS for detecting colorectal liver metastases,the imaging features,the literature reports of metastases in CEUS as well as its technique,its clinical role and its potential applications.Additionally,the updated international consensus panel guidelines are reported in this review with the inherent limitations of this technique and best practice experiences.

Effect of contrast-enhanced ultrasound on differential diagnosis of intrahepatic cholangiocarcinoma and arterial phase enhanced hepatic inflammatory lesions

Objective: To investigate differential diagnosis between intrahepatic cholangiocarcinoma (ICC) and arterial phase enhanced hepatic inflammatory lesions in patients without liver cirrhosis using contrast-enhanced ultrasound (CEUS). Methods: ICC and hepatic inflammatory lesions cases with CEUS and pathological diagnosis between Sep 2013 and Oct 2016 were investigated retrospectively. Imaging features of conventional ultrasound and CEUS were analyzed. The parameters of time intensity curve (TIC), including the arrival time, peak intensity (PI) in the lesions, the starting time for washout, and the intensity difference at 3 min (Delta I-3) after contrast agent infection between the lesion and the liver parenchyma, were compared between ICC and hepatic inflammatory lesions. Results: Twenty-five ICC and fifteen inflammatory patients were included in this study. Seventeen ICC (68.0%) and two inflammatory cases (13.3%) showed bile duct dilatation on conventional ultrasound. Using CEUS, three ICC cases (12.0%) were misdiagnosed as inflammatory lesions and three inflammatory lesions (20.0%) as ICC; two ICC (8.0%) and one inflammatory case (6.7%) could not be made definite diagnosis. Washout started at 34.5 +/- 3.5 s and 61.5 +/- 12.9 s for ICC and inflammatory lesions respectively (P < 0.001). The intensity difference between lesion and liver parenchyma at 3 min after contrast agent injection was 10.8 +/- 3.1 dB in ICC and 4.2 +/- 2.3 dB in inflammatory group (P < 0.001). The sensitivity and specificity differentiating ICC and inflammatory lesions were 76% and 87% if the cut-off value of the intensity difference was 7.7 dB. Conclusions: Combined with TIC analysis, and particularly with the characteristic of the early-starting and obvious washout in ICC, CEUS can be useful in differential diagnosis between hepatic inflammatory lesions and ICC.

Contrast-enhanced ultrasound evaluation of hepatic microvascular changes in liver diseases

AIM： To assess if software assisted-contrast-enhanced ultrasonography （CEUS） provides reproducible perfu- sion parameters of hepatic parenchyma in patients af- fected by chronic liver disease. METHODS： Forty patients with chronic viral liver dis- ease, with （n = 20） or without （n = 20） cirrhosis, and 10 healthy subjects underwent CEUS and video re- cordings of each examination were then analysed with Esaote＇s Qontrast software. CEUS dedicated software Qontrast was used to determine peak （the maximum signal intensity）, time to peak （TTP）, region of blood value （RBV） proportional to the area under the time- intensity curve, mean transit time （MTT） measured in seconds and region of blood flow （RBF）. RESULTS： Qontrast-assisted CEUS parameters dis- played high inter-observer reproducibility （κ： coefficients of 0.87 for MTT and 0.90 TTP）. When the region of in-terest included a main hepatic vein, Qontrast-calculated TTP was significantly shorter in cirrhotic patients （vs non-cirrhotics and healthy subjects） （71.0 ± 11.3 s vs 82.4±15.6 s, 86.3±20.3 s, P 〈 0.05）. MTIs in the patients with liver cirrhosis were significantly shorter than those of controls （111.9±22.0 s vs 139.4±39.8 s, P 〈 0.05）, but there was no significant difference between the cirrhotic and non-cirrhotic groups （111.9± 22.0 s vs 110.3 ±14.6 s）. Peak enhancement in the patients with liver cirrhosis was also higher than that observed in controls （23.9± 5.9 vs 18.9±7.1, P = 0.05）. There were no significant intergroup differences in the RBVs and RBFs. CONCLUSION： Qontrast-assisted CEUS revealed re- producible differences in liver perfusion parameters during the development of hepatic fibrogenesis.

Can contrast enhanced ultrasound differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma?

BACKGROUND Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC)differ in treatment and prognosis,warranting an effective differential diagnosis between them.The LR-M category in the contrast-enhanced ultrasound(CEUS)liver imaging reporting and data system(LI-RADS)was set up for lesions that are malignant but not specific to HCC.However,a substantial number of HCC cases in this category elevated the diagnostic challenge.AIM To investigate the possibility and efficacy of differentiating ICC from HCC classified in the LR-M category according to the CEUS LI-RADS.METHODS Patients with complete CEUS records together with pathologically confirmed ICC and LR-M HCC(HCC classified in the CEUS LI-RADS LR-M category)between January 2015 and October 2018 were included in this retrospective study.Each ICC was assigned a category as per the CEUS LI-RADS.The enhancement pattern,washout timing,and washout degree between the ICC and LR-M HCC were compared using theχ2 test.Logistic regression analysis was used for prediction of ICC.Receiver operating characteristic(ROC)curve analysis was used to investigate the possibility of LR-M criteria and serum tumor markers in differentiating ICC from LR-M HCC.RESULTS A total of 228 nodules(99 ICCs and 129 LR-M HCCs)in 228 patients were included.The mean sizes of ICC and LR-M HCC were 6.3±2.8 cm and 5.5±3.5 cm,respectively(P=0.03).Peripheral rim-like arterial phase hyperenhancement(APHE)was detected in 50.5%(50/99)of ICCs vs 16.3%(21/129)of LR-M HCCs(P<0.001).Early washout was found in 93.4%(93/99)of ICCs vs 96.1%(124/129)of LR-M HCCs(P>0.05).Marked washout was observed in 23.2%(23/99)of ICCs and 7.8%(10/129)of LR-M HCCs(P=0.002),while this feature did not show up alone either in ICC or LR-M HCC.Homogeneous hyperenhancement was detected in 15.2%(15/99)of ICCs and 37.2%(48/129)of LR-M HCCs(P<0.001).The logistic regression showed that rim APHE,carbohydrate antigen 19-9(CA 19-9),and alpha fetoprotein(AFP)had significant correlations with ICC(r=1.251,3.074,and-2.767,respectively;P<0.01).Rim APHE presented the best enhancement pattern for diagnosing ICC,with an area under the ROC curve(AUC)of 0.70,sensitivity of 70.4%,and specificity of 68.8%.When rim hyperenhancement was coupled with elevated CA 19-9 and normal AFP,the AUC and sensitivity improved to 0.82 and 100%,respectively,with specificity decreasing to 63.9%.CONCLUSION Rim APHE is a key predictor for differentiating ICC from LR-M HCC.Rim APHE plus elevated CA 19-9 and normal AFP is a strong predictor of ICC rather than LR-M HCC.Early washout and marked washout have limited value for the differentiation between the two entities.

Diagnostic value of contrast enhanced ultrasound for splenic artery complications following acute pancreatitis

AIM: To assess the value of contrast-enhanced ultrasound (CEUS) in diagnosing splenic artery complications (SACs) after acute pancreatitis (AP). METHODS: One hundred and eighteen patients with AP were enrolled in the study. All patients were examined by CEUS and contrast-enhanced computed tomography (CECT). CECT was accepted as a gold standard for the diagnosis of SACs in AP. The diagnostic accuracy of splenic CEUS and pancreatic CEUS was compared with that of CECT. Splenic infarction was the diagnostic criterion for splenic artery embolism and local dysperfusion of the splenic parenchyma was the diagnostic criterion for splenic arterial stenosis. The incidence of splenic sub-capsular hemorrhage, splenic artery aneurysms, and splenic rupture was all lower than that of SACs. RESULTS: Nine patients were diagnosed as having SACs after AP by CECT among the 118 patients. The patients with SACs were diagnosed with severe acute pancreatitis (SAP). Among them, 6 lesions were diagnosed as splenic artery embolism, 5 as splenic artery aneurysms, and 1 as splenic arterial stenosis. No lesion was diagnosed by pancreatic CEUS and 5 lesions were diagnosed by splenic CEUS. By splenic CEUS, 4 cases were diagnosed as splenic artery embolism and 1 as splenic arterial stenosis. The accuracy of splenic CEUS in diagnosis of SACs in SAP was 41.7% (5/12), which was higher than that of pancreatic CEUS (0%). CONCLUSION: Splenic CEUS is a supplementary method for pancreatic CEUS in AP patients, which can decrease missed diagnosis of SACs. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Role of Contrast Enhanced Ultrasound in Radiofrequency Ablation of Metastatic Liver Carcinoma

Objective： To investigate the application of contrast enhanced ultrasound （CEUS） in planning and guiding for radiofrequency ablation （RFA） for metastatic liver carcinoma （MLC）. Methods： One hundred and thirty-five patients with clinically and pathologically diagnosed MLC （from gastrointestinal tumors） were included in the present study, and 104 of them had received CEUS prior to RFA to assess the number, size, shape, infiltration, location and enhancing features of the lesions. Among the 204 patients, 21 （20.1%） were excluded from RFA treatment due to too many lesions or large infiltrative range based on CEUS. The remaining 83 patients with 147 lesions underwent RFA （group A）. During the same period, other 32 patients with 202 lesions serving as control group were treated based on findings of conventional ultrasound without contrast （group B）. The patients underwent follow-up enhanced CT at the 1st month, and then every 3-6 months after RFA. The tumor was considered as early necrosis if no contrast enhancement was detected in the treated area on the CT scan at the 2st month. Results： In group A, 72 of 147 MLC lesions （48.9%） showed increased sizes on CEUS. Among them, 48 lesions （66.6%） appeared enlarged in arterial phase, and 24 （33.3%） showed enlarged hypoechoic area in parenchymal phase. CEUS showed total 61 additional lesions in 35 patients （42.2%） （ranged from 8 to 15 mm） compared with conventional ultrasound （US）, and 42 （68.8%） of them were visualized in parenchymal phase only. There were total 208 lesions in group A underwent RFA with CEUS planning, and the tumor necrosis rate was 94.2% （196/208）. In this group, local recurrence was found in 26 lesions （7.7%） during 3-42 months＇ following up, and new metastases were seen in 30 cases （36.2%）. For group B, the tumor necrosis rate was 86.3% （88/202）, local recurrence in 27 lesions （16.7%）, and new metastases in 13 cases （41.9%）. Tumor early necrosis and recurrence rates were significantly different between the two groups （P=0.018, P=0.016, respectively）. Conclusion： CEUS played an important role in RFA for liver metastases by candidate selecting and therapy planning, which helped to improve the outcome of the treatment.

Differentiation of atypical hepatic hemangioma from liver metastases: Diagnostic performance of a novel type of color contrast enhanced ultrasound

BACKGROUND In clinical practice,the diagnosis is sometimes difficult with contrast-enhanced ultrasound(CEUS)when the case has an atypical perfusion pattern.Color parametric imaging(CPI)is an analysis software for CEUS with better detection of temporal differences in CEUS imaging using arbitrary colors.It measures the differences in arrival time of the contrast agent in lesions so that the perfusion features of atypical hemangioma and colorectal cancer(CRC)liver metastasis can be distinguished.AIM To evaluate the role of a novel type of CPI of CEUS in the differential diagnosis of atypical hemangioma from liver metastases in patients with a history of CRC.METHODS From January 2016 to July 2018,42 patients including 20 cases of atypical hemangioma and 22 cases of liver metastases from CRC were enrolled.These patients had a mean age of 60.5±9.3 years(range:39-75 years).All patients received ultrasound,CEUS and CPI examinations.Resident and staff radiologists independently and retrospectively reviewed CEUS and CPI images.Two sets of criteria were assigned:(1)Routine CEUS alone;and(2)CEUS and CPI.The diagnostic sensitivity,specificity,accuracy and receiver operating characteristic(ROC)curve of resident and staff radiologists were analyzed.RESULTS The following CPI features were significantly different between liver hemangioma and liver metastases analyzed by staff and resident radiologists:Peripheral nodular enhancement(65%-70.0%vs 4.5%-13.6%,P<0.001,P=0.001),mosaic/chaotic enhancement(5%-10%vs 68.2%-63.6%,P<0.001,P<0.001)and feeding artery(20%vs 59.1%-54.5%,P=0.010,P=0.021).CPI imaging offered significant improvements in detection rates compared with routine CEUS in both resident and staff groups.By resident radiologists,the specificity and accuracy of CEUS+CPI were significantly increased compared with that of CEUS(77.3%vs 45.5%,P=0.030;78.6%vs 50.0%,P=0.006).In addition,the area under the curve(AUC)of CEUS+CPI was significantly higher than that of CEUS(0.803 vs 0.757,P=0.036).By staff radiologists,accuracy was improved in CEUS+CPI(81.0%vs 54.8%,P=0.010),whereas no significant differences in specificity and sensitivity were found(P=0.144,P=0.112).The AUC of CEUS+CPI was significantly higher than that of CEUS(0.890 vs 0.825,P=0.013)by staff radiologists.CONCLUSION Compared with routine CEUS,CPI could provide specific information on the hemodynamic features of liver lesions and help to differentiate atypical hemangioma from liver metastases in patients with CRC,even for senior radiologists.

Contrast-enhanced ultrasound imaging for intestinal lymphoma

BACKGROUND Intestinal lymphoma is a rare tumor.Contrast-enhanced ultrasound(CEUS)findings of intestinal lymphoma have not been reported previously,and the relationship between CEUS and clinicopathological features and prognostic factors is still unknown.AIM To describe the B-mode US and CEUS features of intestinal lymphoma and investigate the correlation of CEUS and histopathological features.METHODS This was a single-center retrospective study.Eighteen patients with histologically confirmed intestinal lymphoma underwent B-mode US and CEUS examinations between October 2016 and November 2019.We summarized the features of Bmode US and CUES imaging of intestinal lymphoma and compared the frequency of tumor necrosis in intestinal lymphomas with reference to different pathological subtypes(aggressive or indolent)and clinical stage(early or advanced).The time–intensity curve parameters of CEUS were also compared between patients with normal and elevated serum lactate dehydrogenase.RESULTS In B-mode imaging,four patterns were observed in intestinal lymphoma:Mass type(12/18,66.7%),infiltration type(1/18,5.6%),mesentery type(4/18,22.2%)and mixed type(1/18,5.6%).All cases were hypoechoic and no cystic areas were detected.On CEUS,most cases(17/18,94.4%)showed arterial hyperechoic enhancement.All cases showed arterial enhancement followed by venous wash out.A relatively high rate of tumor necrosis(11/18,61.1%)was observed in this study.Tumor necrosis on CEUS was more frequent in aggressive subtypes(10/13,76.9%)than in indolent subtypes(1/5,20.0%)(P=0.047).There were no correlations between tumor necrosis and lesion size and Ann Arbor stage.There was no significant difference in time–intensity curve parameters between normal and elevated lactate dehydrogenase groups.CONCLUSION B-mode US and CEUS findings of intestinal lymphoma are characteristic.We observed a high rate of tumor necrosis,which appeared more frequently in aggressive pathological subtypes of intestinal lymphoma.

Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma

BACKGROUND：Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection.It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations.The study aimed to illustrate characteristics of contrast-enhanced ultrasound（CEUS）and its diagnostic value in gallbladder adenoma.METHODS： Thirty-seven patients with 39 gallbladder adenoma- toid lesions （maximal diameter _〉10 mm and without metastasis） were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individuaUy among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. RESULTS： Adenoma lesions showed iso-echogenicity in ul- trasound, and an eccentric enhancement pattern, ＂fast-in and synchronous-out＂ contrast enhancement pattern and homo- geneous at peak-time enhancement in CEUS. The homogenic- ity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion （100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively）. The characteristic of the eccentric enhance- ment pattern had the highest diagnostic ability in differenti- ating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively.CONCLUSIONS： CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps （〉_10 mm in diameter）. Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

Contrast enhanced ultrasound in diagnosing liver lesion that spontaneously disappeared:A case report

BACKGROUND Focal liver lesions(FLLs)are abnormal masses that are distinguishable from the surrounding liver parenchyma,solid or cystic and may be benign or malignant.They are usually detected incidentally on abdominal examinations.The classification of FLLs is very important as it directly determines the diagnosis and treatment of patients.CASE SUMMARY A 46-year-old male patient was admitted into the hospital with tarry stool,during the investigation of this issue an incidental FLL was detected.Upon further investigation of this“incidentaloma”computerized tomography and magnetic resonance imaging reached contradictory conclusions.The lesion was then further investigated using contrast-enhanced ultrasound(CEUS)with an initial diagnosis of idiopathic FLL was acquired and observation of the FLL over time need for final diagnosis,however in the follow up the FLL disappeared spontaneously.CONCLUSION CEUSs value for characterization of FLLs is undeniable,especially when other methods produce inconsistent results,is undeniable but with its limitations.Why and how the FLL disappeared is not known,and can be only hypothesized it was a pseudolesion.

Application Value of Contrast-Enhanced Ultrasound in the Diagnosis of Breast Lesions

Objective:To explore the value and effect of contrast-enhanced ultrasound in the diagnosis of breast lesions.Methods:Seventy-two patients with breast lesions in Shaanxi Provincial People’s Hospital from June 2020 to December 2021 were selected as the research subjects.All 72 patients met the diagnostic criteria of breast lesions.Two patients with incomplete clinical data were excluded;hence,there were 70 patients remaining.The diagnostic results of the two examination methods and the diagnostic value of the joint examination for breast lesions were analyzed and compared.Results:The results of benign,malignant,missed,and misdiagnosed breast lesions by contrast-enhanced ultrasound were 31,32,6,and 1 cases,respectively,accounting for 44.29%,45.71%,8.57%,and 1.43%,respectively.The results of benign,malignant,missed,and misdiagnosed breast lesions by ultrasound automatic volume imaging were 21,24,17,and 8 cases,respectively,accounting for 30.00%,34.28%,24.29%,and 11.43%,respectively.There were statistical differences between the two groups for missed diagnosis and misdiagnosis,but there was no significant difference between the two groups for benign and malignant lesions.The accuracy,sensitivity,and specificity of contrast-enhanced ultrasound were 87.69%,83.62%,and 83.45%,respectively;the accuracy,sensitivity,and specificity of ultrasound automatic volume imaging were 71.39%,68.99%,and 74.69%,respectively;the accuracy,sensitivity,and specificity of contrast-enhanced ultrasound combined with ultrasound automatic volume imaging were 96.29%,92.68%,and 91.78%,respectively.Conclusion:Contrast-enhanced ultrasonography has a high clinical application value and a low inspection error rate in the diagnosis of breast lesions.It merits clinical advancement since it helps doctors diagnose and treat breast lesions more effectively.

A Modified CycleGAN for Multi-Organ Ultrasound Image Enhancement via Unpaired Pre-Training

Handheld ultrasound devices are known for their portability and affordability,making them widely utilized in underdeveloped areas and community healthcare for rapid diagnosis and early screening.However,the image quality of handheld ultrasound devices is not always satisfactory due to the limited equipment size,which hinders accurate diagnoses by doctors.At the same time,paired ultrasound images are difficult to obtain from the clinic because imaging process is complicated.Therefore,we propose a modified cycle generative adversarial network(cycleGAN) for ultrasound image enhancement from multiple organs via unpaired pre-training.We introduce an ultrasound image pre-training method that does not require paired images,alleviating the requirement for large-scale paired datasets.We also propose an enhanced block with different structures in the pre-training and fine-tuning phases,which can help achieve the goals of different training phases.To improve the robustness of the model,we add Gaussian noise to the training images as data augmentation.Our approach is effective in obtaining the best quantitative evaluation results using a small number of parameters and less training costs to improve the quality of handheld ultrasound devices.

Role of contrast enhanced ultrasound in detection of abdominal aortic abnormalities in comparison with multislice computed tomography

Conventional ultrasound （US） is the most widely used imaging modality in routine clinical practice worldwide. The limitations of conventional ultrasound in the detection of aortic lesions versus multi-slice computed tomography angiography （MS-CTA） are well known.

Contrast-enhanced 3D ultrasound in the radiofrequency ablation of liver tumors

Liver metastases and hepatocellular carcinomas are two of the most common causes of cancer deaths in the world.Radiofrequency ablation(RFA) is a well recognized,effective and minimally invasive means of treating malignant hepatic tumors.This article describes the use of contrast-enhanced 3D ultrasound(CE-3DUS) in the staging,targeting and follow-up of patients with liver tumors undergoing RFA.In particular,its value in the management of large hepatic lesions will be illustrated.Current limitations of CE-3DUS and future developments in the technique will also be discussed.In summary,CE-3DUS is useful in the RFA of liver tumors with improved detection and display of occult lesions and recurrence,in the assessment of lesional geometry and orientation for a more accurate planning and guidance of multiple RFA needle electrodes in large tumors and in the evaluation of residual or recurrent disease within the immediate and/or subsequent follow-up periods.

Contrast-enhanced sonography versus biopsy for the differential diagnosis of thrombosis in hepatocellular carcinoma patients

AIM:To clarify which method has accuracy:2nd gen-eration contrast-enhanced ultrasound or biopsy of portal vein thrombus in the differential diagnosis of portal vein thrombosis.METHODS:One hundred and eighty-six patients with hepatocellular carcinoma and portal vein thrombosis underwent in blinded fashion a 2nd generation contrast-enhanced ultrasound and biopsy of portal vein thrombus;both results were examined on the basis of the follow-up of patients compared to reference-standard.RESULTS:One hundred and eight patients completed the study.Benign thrombosis on 2nd generation contrast-enhanced ultrasound was characterised by progressive hypoenhancing of the thrombus;in malignant portal vein thrombosis there was a precocious homo-geneous enhancement of the thrombus.On follow-up there were 50 of 108 patients with benign thrombosis:all were correctly diagnosed by both methods.There were 58 of 108 patients with malignant thrombosis:amongst these,52 were correctly diagnosed by both methods,the remainder did not present malignant cells on portal vein thrombus biopsy and showed on 2nd generation contrast-enhanced ultrasound an inho-mogeneous enhancement pattern.A new biopsy during the follow-up,guided to the area of thrombus that showed up on 2nd generation contrast-enhanced ultra-sound,demonstrated an enhancing pattern indicating malignant cells.CONCLUSION:In patients with hepatocellular carcinoma complicated by portal vein thrombosis,2nd generation contrast-enhanced ultrasound of portal vein thrombus is very useful in assessing the benign or malignant nature of the thrombus.Puncture biopsy of thrombus is usually accurate but presents some sampling errors,so,when pathological results are required,2nd generation contrast-enhanced ultrasound could guide the sampling needle to the correct area of the thrombus.

Contrast-enhanced ultrasonography parameters in neural network diagnosis of liver tumors

AIM:To study the role of time-intensity curve(TIC) analysis parameters in a complex system of neural networks designed to classify liver tumors.METHODS:We prospectively included 112 patients with hepatocellular carcinoma(HCC)(n = 41),hypervascular(n = 20) and hypovascular(n = 12) liver metastases,hepatic hemangiomas(n = 16) or focal fatty changes(n = 23) who underwent contrast-enhanced ultrasonography in the Research Center of Gastroenterology and Hepatology,Craiova,Romania.We recorded full length movies of all contrast uptake phases and post-processed them offline by selecting two areas of interest(one for the tumor and one for the healthy surrounding parenchyma) and consecutive TIC analysis.The difference in maximum intensities,the time to reaching them and the aspect of the late/portal phase,as quantified by the neural network and a ratio between median intensities of the central and peripheral areas were analyzed by a feed forward back propagation multi-layer neural network which was trained to classify data into five distinct classes,corresponding to each type of liver lesion.RESULTS:The neural network had 94.45% training accuracy(95% CI:89.31%-97.21%) and 87.12% testing accuracy(95% CI:86.83%-93.17%).The automatic classification process registered 93.2% sensitivity,89.7% specificity,94.42% positive predictive value and 87.57% negative predictive value.The artificial neural networks(ANN) incorrectly classified as hemangyomas three HCC cases and two hypervascular metastases,while in turn misclassifying four liver hemangyomas as HCC(one case) and hypervascular metastases(three cases).Comparatively,human interpretation of TICs showed 94.1% sensitivity,90.7% specificity,95.11% positive predictive value and 88.89% negative predictive value.The accuracy and specificity of the ANN diagnosis system was similar to that of human interpretation of the TICs(P = 0.225 and P = 0.451,respectively).Hepatocellular carcinoma cases showed contrast uptake during the arterial phase followed by wash-out in the portal and first seconds of the late phases.For the hypovascular metastases did not show significant contrast uptake during the arterial phase,which resulted in negative differences between the maximum intensities.We registered wash-out in the late phase for most of the hypervascular metastases.Liver hemangiomas had contrast uptake in the arterial phase without agent wash-out in the portallate phases.The focal fatty changes did not show any differences from surrounding liver parenchyma,resulting in similar TIC patterns and extracted parameters.CONCLUSION:Neural network analysis of contrastenhanced ultrasonography-obtained TICs seems a promising field of development for future techniques,providing fast and reliable diagnostic aid for the clinician.

Multi-modality parathyroid imaging:A shifting paradigm

The goal of parathyroid imaging in hyperparathyroidism is not diagnosis,rather it is the localization of the cause of hyperparathyroidism for planning the best therapeutic approach.Hence,the role of imaging to accurately and precisely localize the abnormal parathyroid tissue is more important than ever to facilitate minimally invasive parathyroidectomy over bilateral neck exploration.The common causes include solitary parathyroid adenoma,multiple parathyroid adenomas,parathyroid hyperplasia and parathyroid carcinoma.It is highly imperative for the radiologist to be cautious of the mimics of parathyroid lesions like thyroid nodules and lymph nodes and be able to differentiate them on imaging.The various imaging modalities available include high resolution ultrasound of the neck,nuclear imaging studies,four-dimensional computed tomography(4D CT)and magnetic resonance imaging.Contrast enhanced ultrasound is a novel technique which has been recently added to the armam-entarium to differentiate between parathyroid adenomas and its mimics.Through this review article we wish to review the imaging features of parathyroid lesions on various imaging modalities and present an algorithm to guide their radiological differentiation from mimics.

Ultrasound-mediated drug-free theranostics for treatment of prostate cancer

Lipid-shelled nanobubbles(NBs)can be visualized and activated using noninvasive ultrasound(US)stimulation,leading to significant bioeffects.Prior work demonstrates that active targeting of NBs to prostate-specific membrane antigen(PSMA)overexpressed in prostate cancer(PCa)results in enhanced cellular internalization and prolongs NB retention with persistent,cancer-cell specific acoustic activity.In this work,we hypothesized that tumor-accumulated PSMA-NBs combined with low frequency unfocused therapeutic US(TUS)will lead to selective damage and induce a specific therapeutic effect in PSMA-expressing tumors compared to PSMA-negative tumors.We observed that the internalized NBs and cellular compartments were disrupted after the PSMA-NB+TUS(targeted NB therapy or TNT)application,yet treated cells remained intact and viable.In vivo,PSMA-expressing tumors in mice receiving TNT treatment demonstrated a significantly greater extent of apoptosis(78.4±9.3%,p<0.01)compared to controls.TNT treatment significantly inhibited the PSMA expressing tumor growth and increased median survival time by 103%,p<0.001).A significant reduction in tumor progression compared to untreated control was also seen in an orthotopic rabbit PCa model.Results demonstrate that cavitation of PSMA-NBs internalized via receptor-mediated endocytosis into target PCa cells using unfocused ultrasound results in significant,tumor-specific bioeffects.The effects,while not lethal to PSMA-expressing cancer cells in vitro,result in significant in vivo reduction in tumor progression in two models of PCa.While the mechanism of action of these effects is yet unclear,it is likely related to a locally-induced immune response,opening the door to future investigations in this area.

Imaging of liver cancer

Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identif ication and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality.