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.

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.

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 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.

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.

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 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.

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.

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.

Cavernous hemangioma of an intrapancreatic accessory spleen mimicking a pancreatic tumor:A case report

BACKGROUND Intrapancreatic accessory spleen(IPAS)is an uncommon condition,with the majority of cases presenting as solid lesions.Thus,this condition is frequently misdiagnosed as pancreatic solid neoplasm.Moreover,splenic cavernous hemangioma is a rare disorder,whereas lesions with a cystic appearance arising from IPAS have not been reported.CASE SUMMARY Herein,we present a case involving a 32-year-old male who had a complex cystic lesion in the tail of the pancreas revealed by conventional ultrasound.The lesion was misdiagnosed as a pancreatic cystadenoma because of its confusing anatomic location,as well as due to its peripheral nodular and internal septal enhancement patterns on contrast-enhanced ultrasound.After multidisciplinary discussion,the patient finally underwent laparoscopic pancreatic body and tail resections.Postoperative pathology demonstrated the lesion to be a cavernous hemangioma arising from the IPAS.CONCLUSION Cavernous hemangioma in the intrapancreatic accessory spleen may mimic pancreatic cystadenoma,which is a condition with the potential to be malignant.Imaging follow-ups or surgical interventions may be helpful for the exclusion of malignant risks in complicated cystic lesions,especially those with parietal and septal enhancements.

High mechanical index post-contrast ultrasonography improves tissue structural display of hepatocellular carcinoma

Background The advent of second generation agent-SonoVue and low mechanical index real-time contrast enhanced ultrasonography （CEUS） imaging have been shown to improve the diagnostic performance of uhrasonography in hepatocellular carcinoma （HCC）. But no report has described the effect of high mechanical index （MI） post-CEUS. This study aimed to investigate the value of post-CEUS in displaying tissue structures of HCC. Methods Seventy-six HCCs in 65 patients were included in the study. Each patient underwent three scans, high-MI （ MI ： 0. 15 - 1.6 ） pre-contrast ultrasound, low-MI （ MI ： 0. 04 - 0. 08 ） CEUS with contrast agent SonoVue, and high-MI post-contrast ultrasound, which was performed within 3 minutes after CEUS. The size, boundary, echogenicity, internal echotexture and posterior acoustic enhancement of the HCCs in the conventional scans before and after CEUS were evaluated. According to pathological evidence, diagnosis rates of pre-contrast, CEUS and post-contrast scans were determined and compared. The potential mechanism of post-contrast ultrasound imaging was also discussed. Results Compared with pre-contrast, post-contrast ultrasound showed improvement in image quality in most HCCs： twenty-six （34. 2% ） more lesions showed well defined margins and fourteen （18.4%） more nodules showed halo sign; twenty-three （30. 3% ） lesions demonstrated enlarged in sizes; changes in echogenicity were seen in 30 lesions （39.5%） ; eighteen （23.7%） more lesions showed heterogenecity and 20 （26. 3% ） more lesions showed “mosaic”or “nodule-in-nodule” sign; twelve （15.8%） more lesions showed posterior acoustic enhancement. Post-contrast ultrasound showed increased diagnostic accuracy of 93.4% （71/76）, compare with 88.2% （67/76） of CEUS alone. Conclusions High-MI post-contrast ultrasound utilizes harmonic signals during the rupture of microbubbles, and significantly improves the display of echo-characteristics of HCCs in ultrasound images, which adds diagnostic values for CEUS. Post-contrast ultrasound could play an important role in tissue characterization, and may be included in CEUS protocols.