Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma

Objective:Complete resection of malignant gliomas is often challenging.Our previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the total removal of brain lesions.This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.Methods:A total of 64 patients diagnosed with malignant glioma(WHO grade HI and IV)who underwent surgery between 2012 and 2018 were included.Among them,29 patients received ICEUS.The effects of ICEUS on overall survival(OS)and progression-free survival(PFS)of patients were evaluated.A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.Results:The ICEUS group showed better survival rates both in OS and PFS than the control group.The univariate analysis revealed that age,pathology and ICEUS were significant prognostic factors for PFS,with only age being a significant prognostic factor for OS.In multivariate analysis,age and ICEUS were significant prognostic factors for both OS and PFS.The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.Conclusion:ICEUS facilitates the identification of residual tumors.Age and ICEUS are prognostic factors for malignant glioma surgery,and use of ICEUS offers a better prognosis for patients with malignant glioma.

Contrast-enhanced guided endoscopic ultrasound procedures

Contrast-enhanced endoscopic ultrasound(CH-EUS)can overcome the limi-tations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours.Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions,further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS.This review details the knowledge based on the available data on contrast-guided procedures.The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions,which occur in select cases.Additionally,the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage,and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are presented.Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours,in which case CH-EUS can be used to reveal the incomplete tumour destruction.

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

Gastrointestinal contrast-enhanced ultrasonography for diagnosis and treatment of peptic ulcer in children

BACKGROUND The detection rate of peptic ulcer in children is improving,with development of diagnostic procedures.Gastroscopy is the gold standard for the diagnosis of peptic ulcer,but it is an invasive procedure.Gastrointestinal contrast-enhanced ultrasonography(CEUS)has the advantages of being painless,noninvasive,nonradioactive,easy to use,and safe.AIM To investigate the clinical value of CEUS for diagnosis and treatment of peptic ulcer in children.METHODS We investigated 43 children with digestive tract symptoms in our hospital from January 2021 to June 2022.All children were examined by routine ultrasound,gastrointestinal CEUS,and gastroscopy.The pathological results of gastroscopy were taken as the gold standard.Routine ultrasonography was performed before gastrointestinal CEUS.Conventional ultrasound showed the thickness of the gastroduodenal wall,gastric peristalsis,and the adjacent organs and tissues around the abdominal cavity.Gastrointestinal CEUS recorded the thickness of the gastroduodenal wall;the size,location and shape of the ulcer;gastric peristalsis;and adjacent organs and tissues around the abdominal cavity.The results of routine ultrasound and gastrointestinal ultrasound were compared with those of gastroscopy to evaluate the diagnostic results and coincidence rate of routine ultrasound and gastrointestinal CEUS.All children received informed consent from their guardians for CEUS.This study was reviewed and approved by the hospital medical ethics committee.RESULTS Among the 43 children,17(15 male,2 female)were diagnosed with peptic ulcer by gastroscopy.There were 26 children with nonpeptic ulcer.There were eight cases of peptic ulcer and 35 of nonpeptic ulcer diagnosed by conventional ultrasound.The diagnostic coincidence rate of peptic ulcer in children diagnosed by conventional ultrasound was 79.1%(34/43),which was significantly different from that of gastroscopy(P=0.033).It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is low.Fifteen cases of peptic ulcer and 28 of nonpeptic ulcer were diagnosed by CEUS.The diagnostic coincidence rate of peptic ulcer in children was 95.3%(41/43).There was no significant difference between CEUS and gastroscopy(P=0.655).It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is high.CONCLUSION Gastrointestinal CEUS has a high coincidence rate in the diagnosis of peptic ulcer in children,and can be used as a preliminary examination method.

Value of contrast-enhanced ultrasound in deep angiomyxoma using a biplane transrectal probe:A case report

BACKGROUND Deep angiomyxoma(DAM)is a very rare tumor type.Magnetic resonance imaging(MRI)is considered the best imaging modality for diagnosing DAM.Computed tomography(CT)is used mainly to assess the invasion range of DAM.The value of ultrasonography in the diagnosis of DAM is still controversial.Through a literature review,we summarized the current state of ultrasonic examination for DAM and reported for the first time the contrast-enhanced ultrasound(CEUS)features of DAM seen using a biplane transrectal probe.CASE SUMMARY A 37-year-old woman presented with a sacrococcygeal mass that had gradually increased in size over the previous 6 mo.MRI and CT examinations failed to allow a definite diagnosis to be made.Transperineal core needle biopsy(CNB)guided by transrectal ultrasound and CEUS was suggested after a multidisciplinary discussion.Grayscale ultrasound of the lesion showed a layered appearance with alternating hyperechoic and hypoechoic patterns.Transrectal CEUS showed a laminated distribution of the contrast agent that was consistent with the layered appearance of the tumor on grayscale ultrasound.We performed transperineal CNB of the enhanced area inside the tumor under transrectal CEUS guidance and finally made a definitive diagnosis of DAM through histopathology.The patient underwent laparoscopic-assisted transabdominal surgery combined with transperineal surgery for large pelvic tumor resection and pelvic floor peritoneal reconstruction.No recurrence or metastasis was found at the ninemonth follow-up.CONCLUSION Transrectal CEUS can show the layered perfusion characteristics of the contrast agent,guiding subsequent transperineal CNB of the enhanced area within the DAM.

A new method for preparing a rat intracerebral hemorrhage model by combining focused ultrasound and microbubbles

Background:We aimed to prepare a non-invasive,reproducible,and controllable rat model of intracerebral hemorrhage with focused ultrasound(FUS).Methods:A rat intracerebral hemorrhage(ICH)model was established by combining FUS and microbubbles(μBs),and edaravone was used to verify whether the free radical scavenger had a protective effect on the model.The brain tissue of each group was sectioned to observe the gross histology,blood-brain barrier(BBB)permeability,cerebral infarction volume,and histopathological changes.Results:Compared with the FUS group,the BBB permeability was significantly increased in the FUS+μBs(F&B)group(p=0.0021).The second coronal slice in the F&B group had an obvious hemorrhage lesion,and the FUS+μBs+edaravone(F&B&E)group had smaller hemorrhage areas;however,ICH did not occur in the FUS group.The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group(p=0.0030)and F&B&E group(p=0.0208).HE staining results showed that nerve fibrinolysis,neuronal necrosis,microglia production,and erythrocytes were found in both the F&B group and the F&B&E group,but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group.Conclusions:A rat ICH model was successfully prepared using theμBs assisted FUS treatment,and edaravone had a therapeutic effect on this model.This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.

Quantitative evaluation of colorectal tumour vasculature using contrast-enhanced ultrasound:Correlation with angiogenesis and prognostic significance

BACKGROUND Ultrasound is a vital tool for the diagnosis and management of colorectal cancer(CRC).Contrast-enhanced ultrasound(CEUS)is a non-invasive,safe,and cost-effective method for evaluating tumour blood vessels,that play a crucial role in tumour growth and progression.AIM To explore CEUS’s role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis.METHODS This study prospectively enrolled 100 patients with CRC confirmed by histo-pathology.All patients received preoperative CEUS examinations.Quantitative parameters,such as peak intensity(PI),time to peak(TTP),and area under the curve(AUC),were derived from time-intensity curve(TIC)analysis.Tumour tissue samples were obtained during surgery and examined immunohistochem-ically to assess the expression of angiogenesis markers,including vascular endo-thelial growth factor(VEGF)and microvessel density(MVD).The correlation between CEUS parameters,angiogenesis markers,and clinicopathological features was evaluated using appropriate statistical tests.RESULTS Quantitative CEUS parameters(PI,TTP,and AUC)showed significant correlations with VEGF expression(P<0.001)and MVD(P<0.001),indicating a strong link between tumour blood vessels and angiogenesis.Increased PI,reduced TTP,and expanded AUC values were significantly related to higher tumour stage(P<0.001),lymph node metastasis(P<0.001),and distant metastasis(P<0.001).Furthermore,these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis(P<0.001).CONCLUSION CEUS has a high potential in guiding treatment planning and predicting patient outcomes.However,more com-prehensive,multicentre studies are required to validate the clinical utility of CEUS in CRC management.

Evaluation of the Therapeutic Effect of Contrast-Enhanced Ultrasound on Different Types of Knee Osteoarthritis in the Elderly

Objective: To evaluate the curative effect of the Traditional Chinese Medicine (TCM) external therapy on knee osteoarthritis patients with different TCM constitutions using musculoskeletal ultrasonography and contrast-enhanced ultrasonography, and to explore the application value of contrast-enhanced ultrasonography in knee joint diseases. Methods: A total of 57 patients diagnosed with knee osteoarthritis in Shaanxi University of Traditional Chinese Medicine from December 2019 to May 2021 were collected, and they were divided into qi stagnation and blood stasis type group (23 cases) and cold-dampness obstruction type group (34 cases) according to the traditional Chinese medicine method. All patients were given acupuncture combined with TCM fumigation and washing. All patients underwent musculoskeletal ultrasonography and contrast-enhanced ultrasonography before and after treatment, observed and recorded relevant data, and compared the treatment effects between the two groups. Results: 85.96% (49/57) of knee osteoarthritis (KOA) patients had suprapatellar bursa effusion, 42.1% (24/57) had iliotibial band bursae effusion, some of which had poor sound transmission, and thickened synovium was seen in most effusions, 33.33% (19/57) had osteophyte formation. Compared with before treatment, the depth of suprapatellar sac effusion in the Qi stagnation and blood stasis type group decreased after treatment (P Conclusion: Musculoskeletal contrast-enhanced ultrasonography was used to quantitatively evaluate the efficacy of TCM external therapy on KOA for different TCM constitutions. Dynamic observation of synovial lesions of knee osteoarthritis provides a valuable imaging method for evaluating the efficacy of traditional Chinese medicine.

Contrast-enhanced harmonic endoscopic ultrasound imaging: Basic principles, present situation and future perspectives

Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound(EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS(CHEUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration(EUS-FNA) can not only render EUS more accurate but may also assist physicians inmaking decisions when EUS-FNA is inconclusive,increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity.The development of CH-EUS has also opened up exciting possibilities in other research areas,including monitoring responses to anticancer chemotherapy or to ethanolinduced pancreatic tissue ablation,anticancer therapies based on ultrasound-triggered drug and gene delivery,and therapeutic adjuvants by contrast ultrasound-induced apoptosis.Contrast harmonic imaging is gaining popularity because of its efficacy,simplicity and noninvasive nature,and many expectations are currently resting on this technique.If its potential is confirmed in the near future,contrast harmonic imaging will become a standard practice in EUS.

Contrast-enhanced ultrasound in the biliary system:Potential uses and indications

Conventional ultrasound(US)is the first-line imaging investigation for biliary diseases.However,it is lack of the ability to depict the microcirculation of some lesions which may lead to failure in diagnosis for some biliary diseases.The use of contrast-enhanced US(CEUS)has reached the field of bile duct disease in recent years and promising results have been achieved.In this review,the methodology,image interpretation,enhancement pattern,clinical usefulness,and indications for CEUS in the biliary system are summarized.CEUS may be indicated in the biliary system under the following circumstances:(1)Where there is a need to make a characterization of intrahepatic cholangiocarcinoma(ICC);(2)For differentiation diagnosis between ICC and other tumors(i.e.hepatocellular carcinoma or liver metastasis)or infectious diseases;(3)For differentiation diagnosis between biliary cystadenoma and biliary cystadenocarcinoma;(4)To detect malignant change in Caroli’s disease;(5)To depict the extent of Klatskin’s tumor with greater clarity;(6)To make a distinction between gallbladder cholesterol polyp,adenoma and polypoid cancer;(7)To make a distinction between chronic cholecystitis with thickened wall and gallbladder cancer;(8)For differentiation diagnosis between motionless sludge and gallbladder cancer;(9)For differentiation diagnosis between common bile duct cancer and sludge or stone without acoustic shadowing;and(10)In patients who are suspected of having a drop of their percutaneous transhepatic cholangiodrainage tube,US contrast agent can be administered to through the tube detect the site of the tube.

Contrast-enhanced ultrasound in differentiating malignant from benign portal vein thrombosis in hepatocellular carcinoma

Portal vein thrombosis(PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma(HCC) and, in some cases, it may be even the initial sign of an undetected HCC. Detection of malignant PVT in a patient with liver cirrhosis heavily affects the therapeutic strategy. Gray-scale ultrasound(US) is widely unreliable for differentiating benign and malignant thrombi. Although effective for this differential diagnosis, fine-needle biopsy remains an invasive technique. Sensitivity of color-doppler US in detection of malignant thrombi is highly dependent on the size of the thrombus. Contrast-enhanced computed tomography(CT) and contrast-enhanced magnetic resonance(MRI) can be useful to assess the nature of portal thrombus, while limited data are currently available about the role of positron emission tomography(PET) and PET-CT. In contrast with CT, MRI, PET, and PET-CT, contrast-enhanced ultrasound(CEUS) is a fast, effective, well tolerated and cheap technique, that can be performed even in the same session in which the thrombus has been detected. CEUS can be performed bedside and can be available also in transplanted patients. Moreover, CT and MRI only yield a snapshot analysis during contrast diffusion, while CEUS allows for a continuous real-time imaging of the microcirculation that lasts several minutes, so that the whole arterial phase and the late parenchymal phase of the contrast diffusion can be analyzed continuously by real-time US scanning. Continuous real-time monitoring of contrast diffusion entails an easy detection of thrombus maximum enhancement. Moreover, continuous quantitative analyses of enhancement(wash in- wash out studies) by CEUS during contrast diffusion is nowadays available in most CEUS machines, thus giving a more sophisticated and accurate evaluation of the contrast distribution and an increased confidence in diagnosis in difficult cases. In conclusion, CEUS is avery reliable technique with a high intrinsic sensitivity for portal vein patency assessment. More expensive and sophisticated techniques(i.e., CT, MRI, PET, and PET-CT) should only be indicated in undetermined cases at CEUS.

Value of contrast-enhanced ultrasound combined with elastography in evaluating cervical lymph node metastasis in papillary thyroid carcinoma

BACKGROUND Cervical lymph node metastasis in papillary thyroid carcinoma(PTC) affects the treatment and prognosis of patients. Ultrasound is a common imaging method for detecting cervical lymph nodes in PTC patients; however, it is not accurate in determining lymph node metastasis.AIM To evaluate the value of contrast-enhanced ultrasound combined with elastography in evaluating cervical lymph node metastasis in PTC.METHODS A total of 94 patients with PTC were recruited. According to pathological results,lymph nodes were divided into two groups: metastatic group(n = 50) and reactive group(n = 63). The routine ultrasound findings, contrast-enhanced ultrasound and elastography data were recorded and compared. Logistic regression was used to generate predictive probability distributions for the diagnosis of lymph node metastasis with different indicators. Receiver operating characteristic curve analysis was used to test the efficacy of contrast-enhanced ultrasound combined with elastography based on routine ultrasound in evaluating PTC cervical lymph node metastasis.RESULTS The ratio of long diameter/short diameter(L/S) ≤ 2, irregular marginal morphology, missing lymphatic portal, peripheral or mixed blood flow distribution, peak intensity(PI), non-uniform contrast distribution and elasticity score in the metastatic group were significantly higher than those in the reactive group(P < 0.05). L/S ratio, missing lymphatic portal, PI and elasticity score had a significant influence on the occurrence of PTC cervical lymph node metastasis(P< 0.05). Furthermore, the area under the curve(AUC) for lymph node metastasis diagnosed using the combination of PI ratio, elasticity score, missing lymphatic portal and LS was 0.936, which was significantly higher than the AUC for PI ratio alone. The difference was statistically significant(P < 0.05). The fitting equation for the combined diagnosis was logit(P) =-12.341 + 1.482 × L/S ratio + 3.529 ×missing lymphatic portal + 0.392 × PI + 3.288 × elasticity score.CONCLUSION Based on the gray-scale ultrasound, the combination of contrast-enhanced ultrasound and elastography can accurately assess PTC cervical lymph node metastasis.

Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma

The success rate of percutaneous radiofrequency(RF)ablation for hepatocellular carcinoma(HCC)depends on correct targeting via an imaging technique.However,RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound(US),color Doppler,and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue.Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver.Two breakthroughs in the field of US technology,harmonic imaging and the development of second-generation contrast agents,have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions.Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor.Therefore,contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC,which is poorly depicted by B-mode US.The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.

Role of contrast-enhanced ultrasound in follow-up assessment after ablation for hepatocellular carcinoma

AIM:To assess the usefulness of contrast-enhanced ultrasound (CEUS) during follow-up after percutaneous ablation therapy for hepatocellular carcinoma (HCC).METHODS:A total of 141 patients with HCCs who received percutaneous ablation therapy were assessed by paired follow-up CEUS and contrast-enhanced computed tomography (CECT).The follow-up scheme was designed prospectively and the intervals between CEUS and CECT examinations were less than 14 d.Both im-ages of follow-up CEUS and CECT were reviewed by radiologists.The ablated lesions were evaluated and classified as local tumor progression (LTP) and LTPfree.LTP was defined as regrowth of tumor inside or adjacent to the successfully treated nodule.The detected new intrahepatic recurrences were also evaluated and defined as presence of intrahepatic new foci.On CEUS and CECT,LTP and new intrahepatic recurrence both were displayed as typical enhancement pattern of HCC (i.e.,hyper-enhancing during the arterial phase and washout in the late phase).With CECT as the reference standard,the ability of CEUS in detecting LTP or new intrahepatic recurrence during follow-up was evaluated.RESULTS:During a follow-up period of 1-31 mo (median,4 mo),169 paired CEUS and CECT examinations were carried out for the 141 patients.For a total of 221 ablated lesions,266 comparisons between CEUS and CECT findings were performed.Thirty-three LTPs were detected on CEUS whereas 40 LTPs were detected on CECT,there was significant difference (P < 0.001).In comparison with CECT,the numbers of false positive and false negative LTPs detected on CEUS were 6 and 13,respectively;the sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV) and overall accuracy of CEUS in detecting LTPs were 67.5%,97.4%,81.8%,94.4% and 92.3%,respectively.Meanwhile,131 new intrahepatic recurrent foci were detected on CEUS whereas 183 were detected on CECT,there was also significant difference (P < 0.05).In comparison with CECT,the numbers of false positive and false negative intrahepatic recurrences detected on CEUS were 13 and 65,respectively;the sensitivity,specificity,PPV,NPV and overall accuracy of CEUS in detecting new intrahepatic recurrent foci were 77.7%,92.0%,92.4%,76.7% and 84.0%,respectively.CONCLUSION:The sensitivity of CEUS in detecting LTP and new intrahepatic recurrence after percutaneous ablation therapy is relatively low in comparisonwith CECT.

Application of contrast-enhanced ultrasound after livertransplantation:Current status and perspectives

Liver transplantation is an effective treatment for patients with end-stage liver disease. Accurate imaging evaluation of the transplanted patient is critical for ensuring that the limited donor liver is functioning appropriately. Ultrasound contrast agents(UCAs), in combination with contrastspecific imaging techniques, are increasingly accepted in clinical use for the assessment of the hepatic vasculature, bile ducts and liver parenchyma in pre-, intra- and posttransplant patients. We describe UCAs, their technical requirements, the recommended clinical indications, image interpretation and the limitations for contrastenhanced ultrasound applications in liver transplantation.

Contrast-enhanced ultrasound:The evolving applications

Contrast-enhanced ultrasound(CEUS)is a major breakthrough for ultrasound imaging in recent years.By using a microbubble contrast agent and contrast-specific imaging software,CEUS is able to depict the microand macro-circulation of the targeted organ,which in turn leads to improved performance in diagnosis.Due to the special dual blood supply system in the liver,CEUS is particularly suitable for liver imaging.It is evident that CEUS facilitates improvement for characterization of focal liver lesions(FLLs),detection of liver malignancy,guidance for interventional procedures,and evaluation of treatment response after local therapies.CEUS has been demonstrated to be equal to contrast-enhanced computed tomography or magnetic resonance imaging for the characterization of FLLs.In addition,the applicability of CEUS has expanded to non-liver structures such as gallbladder,bile duct,pancreas,kidney,spleen,breast,thyroid,and prostate.The usefulness of CEUS in these applications is confirmed by extensive literature production.Novel applications include detecting bleeding sites and hematomas in patients with abdominal trauma,guiding percutaneous injection therapy and therefore achieving the goal of using interventional ultrasonography in managing splenic trauma,assessing the activity of Crohn’s disease,and detecting suspected endoleaks after endovascular abdominal aneurysm repair.Contrast-enhanced intraoperative ultrasound(US)and intracavitary use of CEUS have been developed and clinically studied.The potential use of CEUS involves sentinel lymph node detection,drug or gene delivery,and molecular imaging.In conclusion,the advent of CEUS has greatly enhanced the usefulness of US and even changed the status of US in clinical practice.The application of CEUS in the clinic is continuously evolving and it is expected that its use will be expanded further in the future.

Contrast-enhanced ultrasound in diagnosis and characterization of focal hepatic lesions

The extensive use of imaging techniques in differential diagnosis of abdominal conditions and screening of hepatocellular carcinoma in patients with chronic hepatic diseases,has led to an important increase in identification of focal liver lesions.The development of contrastenhanced ultrasound(CEUS) opens a new window in the diagnosis and follow-up of these lesions.This technique offers obvious advantages over the computed tomography and magnetic resonance,without a decrease in its sensitivity and specificity.The new second generation contrast agents,due to their intravascular distribution,allow a continuous evaluation of the enhancement pattern,which is crucial in characterization of liver lesions.The dual blood supply in the liver shows three different phases,namely arterial,portal and late phases.The enhancement during portal and late phases can give important information about the lesion's behavior.Each liver lesion has a different enhancement pattern that makes possible an accurate approach to their diagnosis.The role of emerging techniques as a contrastenhanced three-dimensional US is also discussed.In this article,the advantages,indications and technique employed during CEUS and the different enhancement patterns of most benign and malignant focal liver lesions are discussed.

Contrast-enhanced ultrasound improved performance of breast imaging reporting and data system evaluation of critical breast lesions

AIM: To determine whether contrast-enhanced ultrasound(CEUS) can improve the precision of breast imaging reporting and data system(BI-RADS) categorization. METHODS: A total of 230 patients with 235 solid breast lesions classified as BI-RADS 4 on conventional ultrasound were evaluated. CEUS was performed within one week before core needle biopsy or surgical resection and a revised BI-RADS classification was assigned based on 10 CEUS imaging characteristics. Receiver operating characteristic curve analysis was then conducted to evaluate the diagnostic performance of CEUS-based BI-RADS assignment with pathological examination as reference criteria. RESULTS: The CEUS-based BI-RADS evaluation classified 116/235(49.36%) lesions into category 3, 20(8.51%), 13(5.53%) and 12(5.11%) lesions into categories 4A, 4B and 4C, respectively, and 74(31.49%) into category 5. Selecting CEUS-based BI-RADS category 4A as an appropriate cut-off gave sensitivity and specificity values of 85.4% and 87.8%, respectively, for the diagnosisof malignant disease. The cancer-to-biopsy yield was 73.11% with CEUS-based BI-RADS 4A selected as the biopsy threshold compared with 40.85% otherwise, while the biopsy rate was only 42.13% compared with 100% otherwise. Overall, only 4.68% of invasive cancers were misdiagnosed.CONCLUSION: This pilot study suggests that evaluation of BI-RADS 4 breast lesions with CEUS results in reduced biopsy rates and increased cancer-to-biopsy yields.

Ultrasound features of hepatocellular adenoma and the additional value of contrast-enhanced ultrasound

BACKGROUNI）： Hepatocellular adenoma （HCA） is a rare benign tumor of the liver. It is of clinical importance to dif- ferentiate HCA from other liver tumors, especially hepatocel- lular carcinoma （HCC）. This study aimed to evaluate the char- acteristic features of HCA by conventional ultrasound and contrast-enhanced ultrasound （CEUS） findings. METHODS： Twenty-six patients （10 males and 16 females; mean age 36.2＋5.0 years） with 26 histopathologically proven HCAs were retrospectively identified. According to the maxi- mum diameter of HCAs, they were divided into three groups： 〈30 mm, 30-50 mm, and 〉50 mm. Ultrasound examinations were performed with C5-2 broadband curved transducer of Philips iU22 unit （Philips Bothell, WA, USA）. For each lesion, a dose of 2.4 mL SonoVue~ （Bracco Imaging Spa, Milan, Italy） was injected as a quick bolus into the cubital vein. Lesions＇ echogenicity, color-Doppler flow imaging and contrast en- hancement patterns were recorded. RESULTS： Grayscale ultrasound revealed that most of HCAs were hypoechoic （73.1%, 19/26）. Spotty calcifications were detected in 26.9% （7/26） of the lesions. Color-Doppler flow imaging detected centripetal bulky color flow in 46.2% （12/26） of the HCAs. CEUS showed that 73.1% （19/26） of the HCAs displayed as rapid, complete and homogenous enhancement, and 53.8% （14/26） showed decreased contrast enhancement in the late phase. There was no significant difference in enhance- ment patterns among different sizes of HCAs （P〉0.05）. Centripetal enhancement with subcapsular tortuous arteries was common in larger HCAs.

Contrast-enhanced ultrasound imaging of the vasa vasorum of carotid artery plaque

The vasa vasorum of carotid artery plaque is a novel marker of accurately evaluating the vulnerability of carotid artery plaque, which was associated with symptomatic cerebrovascular and cardiovascular disease. The presence of ultrasound contrast agents in carotid artery plaque represents the presence of the vasa vasorum in carotid artery plaque because the ultrasoundcontrast agents are strict intravascular tracers. Therefore, contrast-enhanced ultrasound(CEUS) is a novel and safe imaging modality for evaluating the vasa vasorum in carotid artery plaque. However, there are some issues that needs to be assessed to embody fully the clinical utility of the vasa vasorum in carotid artery plaque with CEUS.