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 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.

Contrast-enhanced harmonic endoscopic ultrasonography for assessment of lymph node metastases in pancreatobiliary carcinoma

AIM: To assess the usefulness of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for lymph node metastasis in pancreatobiliary carcinoma.METHODS: All patients suspected of pancreatobiliary carcinoma with visible lymph nodes after standard EUS between June, 2009 and January, 2012 were enrolled. In the primary analysis, patients with successful EUS-fine needle aspiration (FNA) were included. The lymph nodes were assessed by several standard EUS variables (short and long axis lengths, shape, edge characteristic and echogenicity), color Doppler EUS variable [central intranodal blood vessel (CIV) presence] and CH-EUS variable (heterogeneous/homogeneous enhancement patterns). The diagnostic accuracy relative to EUS-FNA was calculated. In the second analysis, N-stage diagnostic accuracy of CH-EUS was compared with EUS-FNA in patients who underwent surgical resection.RESULTS: One hundred and nine patients (143 lymph nodes) fulfilled the criteria. The short axis cut-off ≥ 13 mm predicted malignancy with a sensitivity and specificity of 72% and 85%, respectively. These values were 72% and 63% for the long axis cut-off ≥ 20 mm, 62% and 75% for the round shape variable, 81% and 30% for the sharp edge variable, 66% and 61% for the hypoechogenicity variable, 70% and 72% for the CIV-absent variable, and 83% and 91% for the heterogeneous CH-EUS-enhancement variable, respectively. CH-EUS was more accurate than standard and color Doppler EUS, except the short axis cut-off. Notably, three patients excluded because of EUS-FNA failure were correctly N-staged by CH-EUS.CONCLUSION: CH-EUS complements standard and color Doppler EUS and EUS-FNA for assessment of lymph node metastases.

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.

Endoscopic techniques for the diagnosis of pancreatic cystic lesions

Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.

Endoscopic ultrasound for the diagnosis of chronic pancreatitis

Endoscopic ultrasound(EUS) has become a well accepted test for the diagnosis of chronic pancreatitis.Advantages include its ability to detect subtle and severe changes of the pancreatic duct and parenchyma,and its relative safety compared with endoscopic retrograde cholangiopancreatography.Limitations include inter-and intraobserver variability,operator dependence,and an incomplete understanding of its true accuracy.The Rosemont classif ication has recently been proposed as a weighted,standardized method that may improve EUS chronic pancreatitis scoring.This paper reviews the published evidence regarding the accuracy of EUS in chronic pancreatitis diagnosis,and enumerates the emerging technologies that have been recently studied which may ultimately improve endosonographic imaging of the pancreas.

New endoscopic ultrasound techniques for digestive tract diseases: A comprehensive review

Endoscopic ultrasound(EUS) is one of the most important modalities for the diagnosis of digestive tract diseases.EUS has been evolving ever since it was introduced.New techniques such as elastography and contrast enhancement have emerged, increasing the accuracy, sensitivity and specificity of EUS for the diagnosis of digestive tract diseases including pancreatic masses and lymphadenopathy.EUS-elastography evaluates tissue elasticity and therefore, can be used to differentiate various lesions.Contrast-enhanced EUS can distinguish benign from malignant pancreatic lesions and lymphadenopathy using the intravenous injection of contrast agents.This review discusses the principles and types of these new techniques, as well as their clinical applications and limitations.

State-of-the-art imaging techniques in endoscopic ultrasound

Endoscopic ultrasound (EUS) has recently evolved through technological improvement of equipment,with a major clinical impact in digestive and mediastinal diseases.State-of-the-art EUS equipment now includes real-time sono-elastography,which might be useful for a better characterization of lesions and increased accuracy of differential diagnosis (for e.g.lymph nodes or focal pancreatic lesions).Contrast-enhanced EUS imaging is also available,and is already being used for the differential diagnosis of focal pancreatic masses.The recent development of low mechanical index contrast harmonic EUS imaging offers hope for improved diagnosis,staging and monitoring of anti-angiogenic treatment.Tridimensional EUS (3D-EUS) techniques can be applied to enhance the spatial understanding of EUS anatomy,especially for improved staging of tumors,obtained through a better assessment of the relationship with major surrounding vessels.Despite the progress gained through all these imaging techniques,they cannot replace cytological or histological diagnosis.However,real-time optical histological diagnosis can be achieved through the use of single-fiber confocal laser endomicroscopy techniques placed under real-time EUS-guidance through a 22G needle.Last,but not least,EUS-assisted natural orifice transluminal endoscopic surgery (NOTES) procedures offer a whole new area of imaging applications,used either for combination of NOTES peritoneoscopy and intraperitoneal EUS,but also for access of retroperitoneal organs through posterior EUS guidance.

Enhanced endoscopic ultrasound imaging for pancreatic lesions: The road to artificial intelligence

Early detection of pancreatic cancer has long eluded clinicians because of its insidious nature and onset.Often metastatic or locally invasive when symptomatic,most patients are deemed inoperable.In those who are symptomatic,multi-modal imaging modalities evaluate and confirm pancreatic ductal adenocarcinoma.In asymptomatic patients,detected pancreatic lesions can be either solid or cystic.The clinical implications of identifying small asymptomatic solid pancreatic lesions(SPLs)of<2 cm are tantamount to a better outcome.The accurate detection of SPLs undoubtedly promotes higher life expectancy when resected early,driving the development of existing imaging tools while promoting more comprehensive screening programs.An imaging tool that has matured in its reiterations and received many image-enhancing adjuncts is endoscopic ultrasound(EUS).It carries significant importance when risk stratifying cystic lesions and has substantial diagnostic value when combined with fine needle aspiration/biopsy(FNA/FNB).Adjuncts to EUS imaging include contrast-enhanced harmonic EUS and EUS-elastography,both having improved the specificity of FNA and FNB.This review intends to compile all existing enhancement modalities and explore ongoing research around the most promising of all adjuncts in the field of EUS imaging,artificial intelligence.

Pancreatico-biliary endoscopic ultrasound:A systematic review of the levels of evidence,performance and outcomes

Our aim was to record pancreaticobiliary endoscopic ultrasound(EUS) literature of the past 3 decades and evaluate its role based on a critical appraisal of published studies according to levels of evidence(LE).Original research articles(randomized controlled trials,prospective and retrospective studies),meta-analyses,reviews and surveys pertinent to gastrointestinal EUS were included.All articles published until September 2011 were retrieved from PubMed and classified according to specific disease entities,anatomical subdivisions and therapeutic applications of EUS.The North of England evidencebased guidelines were used to determine LE.A total of 1089 pertinent articles were reviewed.Published research focused primarily on solid pancreatic neoplasms,followed by disorders of the extrahepatic biliary tree,pancreatic cystic lesions,therapeutic-interventional EUS,chronic and acute pancreatitis.A uniform observation in all six categories of articles was the predominance of LE Ⅲ studies followed by LE Ⅳ,Ⅱb,Ⅱa,Ⅰb and Ⅰ a,in descending order.EUS remains the most accurate method for detecting small(< 3 cm) pancreatic tumors,ampullary neoplasms and small(< 4 mm) bile duct stones,and the best test to define vascular invasion in pancreatic and peri-ampullary neoplasms.Detailed EUS imaging,along with biochemical and molecular cyst fluid analysis,improve the differentiation of pancreatic cysts and help predict their malignant potential.Early diagnosis of chronic pancreatitis appears feasible and reliable.Novel imaging techniques(contrast-enhanced EUS,elastography) seem promising for the evaluation of pancreatic cancer and autoimmune pancreatitis.Therapeutic applications currently involve pancreaticobiliary drainage and targeted fine needle injection-guided antitumor therapy.Despite the ongoing development of extra-corporeal imaging modalities,such as computed tomography,magnetic resonance imaging,and positron emission tomography,EUS still holds a leading role in the investigation of the pancreaticobiliary area.The major challenge of EUS evolution is its expanding therapeutic potential towards an effective and minimally invasive management of complex pancreaticobiliary disorders.

Current role of endoscopic ultrasound in the diagnosis and management of pancreatic cancer

Endoscopic ultrasound(EUS)has emerged as an invaluable tool for the diagnosis,staging and treatment of pancreatic ductal adenocarcinoma(PDAC).EUS is currently the most sensitive imaging tool for the detection of solid pancreatic tumors.Conventional EUS has evolved,and new imaging techniques,such as contrast-enhanced harmonics and elastography,have been developed to improve diagnostic accuracy during the evaluation of focal pancreatic lesions.More recently,evaluation with artificial intelligence has shown promising results to overcome operator-related flaws during EUS imaging evaluation.Currently,an appropriate diagnosis is based on a proper histological assessment,and EUSguided tissue acquisition is the standard procedure for pancreatic sampling.Newly developed cutting needles with core tissue procurement provide the possibility of molecular evaluation for personalized oncological treatment.Interventional EUS has modified the therapeutic approach,primarily for advanced pancreatic cancer.EUS-guided fiducial placement for local targeted radiotherapy treatment or EUS-guided radiofrequency ablation has been developed for local treatment,especially for patients with pancreatic cancer not suitable for surgical resection.Additionally,EUS-guided therapeutic procedures,such as celiac plexus neurolysis for pain control and EUS-guided biliary drainage for biliary obstruction,have dramatically improved in recent years toward a more effective and less invasive procedure to palliate complications related to PDAC.All the current benefits of EUS in the diagnosis and management of PDAC will be thoroughly discussed.

超声内镜在胃肠道间质瘤诊断中的应用进展

胃肠道间质瘤(gastrointestinal stromal tumor,GIST)是具有恶性潜能的间质瘤,不同恶性风险的GIST选择不同的治疗策略,如监测随访、内镜治疗、手术切除或/和药物治疗。因此,GIST的早期诊断以及风险评估对选择合适的治疗方案十分重要。目前,随着内镜技术的广泛应用,超声内镜(endoscopic ultrasound,EUS)、超声内镜弹性成像(endoscopic elastic imaging,EUS-EG)、超声内镜谐波增强(contrast-enhanced harmonic endoscopic ultrasound,CH-EUS)、超声内镜引导下细针抽吸/活检(endoscopic ultrasound-guided fine-needle aspiration/biopsy,EUS-FNA/EUS-FNB)被应用于GIST的诊断以及风险评估。本文主要对以上检查方式在GIST中的应用进行阐述。

超声内镜弹性成像技术联合谐波造影增强超声内镜在胰腺占位性病变中的诊断价值

目的研究胰腺占位性病变检查中超声内镜弹性成像技术(EUS-EG)与谐波造影增强超声内镜(CEH-EUS)联合诊断的价值。方法以回顾性分析为法,观察对象为2022年1月至2023年6月华北医疗健康集团峰峰总医院收治的80例胰腺占位性病变患者,参考不同检查方式分为单一组(仅接受EUS-EG检查,n=80)与联合组(EUS-EG联合CEH-EUS检查,n=80)。比较两组患者的疾病检出率、误诊率、准确度、特异度及敏感度,并比较胰腺良性、恶性病变超声造影时相,观察CEH-EUS、EUS-EG影像学特点。结果以病理学检查结果为诊断金标准,80例胰腺占位性病变患者均行手术切除处理,病理学检验显示44例为良性病变,36例为恶性病变。两组患者疾病检出率差异无统计学意义(P>0.05);联合组疾病误诊率(5.00%)明显低于单一组(30.00%),差异有统计学意义(P<0.05)。联合组诊断准确性、敏感度分别为95.00%、97.36%,均明显高于单一组(70.00%、67.85%),差异均有统计学意义(P<0.05);两组诊断特异度比较,差异无统计学意义(P>0.05)。良性病变的超声造影时相早增晚退、同增同退率分别为22.72%、54.54%,均明显高于恶性病变(0、0),晚增早退率为13.63%,低于恶性病变(55.56%),差异均有统计学意义(P<0.05)。结论EUS-EG与CEH-EUS联合诊断胰腺占位性病变的准确性和敏感度均高于单纯EUS-EG检测,可有效减少误诊。

谐波造影增强超声内镜技术在诊断胰腺实性肿物的作用

目的评价谐波造影增强超声内镜技术对胰腺实性肿物性质诊断的临床价值。方法回顾性选取2018年1月至2021年9月影像学发现胰腺实性肿物,在中山大学肿瘤防治中心行超声内镜及谐波造影增强超声内镜检查的患者134例,比较超声内镜和谐波造影增强超声内镜对胰腺实性肿物诊断与病理学诊断的符合率。结果入组的患者中,胰腺恶性病变有113例,良性病变21例。超声内镜对胰腺实性肿物诊断的敏感度、特异度、诊断的符合率分别为61.9%、52.4%和60.4%;谐波造影增强超声内镜对胰腺实性肿物诊断的敏感性、特异性、诊断的符合率分别为84.1%、80.9%和83.6%,差异有统计学意义(P=0.017)。病理诊断为恶性肿瘤的113例病例中,超声内镜诊断为胰腺腺癌65例,诊断胰腺癌的灵敏度、特异度、诊断符合率分别为65.0%、46.2%和62.8%;谐波造影增强超声内镜诊断为胰腺腺癌88例,诊断胰腺癌的灵敏度、特异度、诊断符合率分别为88.0%、84.6%和87.6%,高于超声内镜检查,差异有统计学意义(P<0.001)。结论谐波造影增强超声内镜技术有助于胰腺肿物良恶性性质的判断,对区分胰腺癌和胰腺其他恶性肿瘤中有较高的临床价值。

谐波造影增强超声内镜诊断胰腺癌的Meta分析

目的评价谐波造影增强超声内镜技术对胰腺癌的诊断价值。方法通过检索PubMed、Embase和Cochrane图书馆等数据库,收集有关谐波造影增强超声内镜技术诊断胰腺实性病变的相关文献,按照纳入和排除标准进行筛查,提取数据,并进行方法学质量评价。采用Stata软件计算谐波造影增强超声内镜诊断胰腺癌的合并敏感性(SE)和特异性(SP),绘制森林图及综合受试者工作特征曲线(SROC),计算曲线下面积(AUC),并探讨异质性程度和来源。结果最终纳入15项研究,共1693例患者,合并SE为0.91(95%CI:0.87~0.94),合并SP为0.79(95%CI:0.71~0.85),SROC AUC为0.93(95%CI:0.90~0.95)。结论谐波造影增强超声内镜对胰腺癌有良好的诊断效能。

Sonography of the small intestine

In the last two decades, there has been substantial development in the diagnostic possibilities for examining the small intestine. Compared with computerized tomography, magnetic resonance imaging, capsule endoscopy and double-balloon endoscopy, ultrasonography has the advantage of being cheap, portable, flexible and user-and patient-friendly, while at the same time providing the clinician with image data of high temporal and spatial resolution. The method has limitations with penetration in obesity and with intestinal air impairing image quality. The flexibility ultrasonography offers the examiner also implies that a systematic approach during scanning is needed. This paper reviews the basic scanning techniques and new modalities such as contrast-enhanced ultrasound, elastography, strain rate imaging, hydrosonography, allergosonography, endoscopic sonography and nutritional imaging, and the literature on disease-specific findings in the small intestine. Some of these methods have shown clinical benefit, while others are under research and development to establish their role in the diagnostic repertoire. However, along with improved overall image quality of new ultrasound scanners, these methodshave enabled more anatomical and physiological changes in the small intestine to be observed. Accordingly, ultrasound of the small intestine is an attractive clinical tool to study patients with a range of diseases.

Small invasive ductal carcinoma of the pancreas distinct from branch duct intraductal papillary mucinous neoplasm

Endoscopic ultrasonography （EUS） is a highly sensitive diagnostic method for the detection of small pancreatic carcinomas. Recently, there have been some reports describing the utility of contrast-enhanced harmonic EUS （CEH-EUS） which uses sonographic contrast agent for differentiation of a pancreatic mass. This report describes a case of small adenocarcinoma of the pancreas distinct from branch duct intraductal papillary mucinous neoplasm （IPMN） in which investigation by EUS took place every 6 mo and diagnosis was made accurately by additional CEH-EUS during the follow-up of the branch duct IPMN. A 68-year-old female was admitted to our hospital because of a branch duct IPMN in the pancreatic body. She had been followed-up by EUS every 6 too. However, after 2 years EUS demonstrated a low echoic area distinct from the branch duct IPMN which was vaguely discernible by EUS, and accurate sizing and differential diagnosis were considered difficult on the EUS imaging. CHEUS with Sonazoid revealed a hypovascular tumor and we suspected small pancreatic carcinoma. The histopathological diagnosis was adenocarcinoma （10 mm） in the pancreatic tail, distinct from the branch duct IPMN of the pancreatic body. EUS and CEH-EUS may play an important role in the correct diagnosis of small pancreatic tumors, including synchronous and metachronous occurrence of IPMN and ductal adenocarcinoma of the pancreas.