ICUS Weekly News Monitor 4-20-2018

1.Science Daily, Detailed images of tumor vasculature - Medical engineering, April 18,2018, By tracking individual microbubbles, high-resolution images can be taken with conventional ultrasound scanners, April 18, 2018

2.Journal of the American Society of Echocardiography, Clinical Use of Ultrasound Enhancing Agents; Contrast-Enhanced Echocardiography Has the Greatest Impact in Patients with Reduced Ejection Fractions, March, 2018 Authors: Hang Zhao MD, et al

Science Daily

Detailed images of tumor vasculature - Medical engineering

By tracking individual microbubbles, high-resolution images can be taken with conventional ultrasound scanners.

April 18, 2018

Ruhr-University Bochum. "Detailed images of tumor vasculature: Medical engineering." ScienceDaily, 18 April 2018. <>.


Thanks to a new method of analyzing ultrasound images, conventional scanners can be used for generating high-res images of blood vessels in tumors. This approach makes it easier to distinguish between different types of tumors, and it facilitates the tracking of the progress and success of chemotherapy.

The new technology has been developed jointly by teams headed by Prof Dr Georg Schmitz at the Chair for Medical Engineering at Ruhr-Universität Bochum and by Prof Dr Fabian Kiessling at the Institute for Experimental Molecular Imaging at the University Hospital Aachen. They published their report in the journal Nature Communications from April 18, 2018.

Monitoring microbubbles on their path through the body

The new technology called "Motion Model Ultrasound Localization Microscopy" is based on contrast medium-enhanced ultrasound images. Microbubbles are administered to patients as contrast agents: gas bubbles no larger than one micrometre that travel through the body in the bloodstream. In ultrasound images, they appear as shapeless white blobs. "Once the centre of each of these blobs has been identified, it's possible to determine the location of individual bubbles," explains Georg Schmitz.

Each bubble is given a name

Using algorithms originally developed for radar technology, the research team successfully monitored the motion of individual microbubbles. "We are currently attempting to teach the computer something that our eyes are able to do: namely read movement in a sequence of images in which a dot appears in different locations," says Schmitz. To this end, the researchers gave each bubble a name. Thus, they were able to track their paths through the vascular system and count them in the process.

Resolution much higher than mere image resolution

Subsequently, fine vascular networks can be reconstructed based on the motion of the bubbles. The direction and speed of the blood flow can likewise be recorded. The resolution of the images is greatly enhanced: experts refer to the technique as super-resolution imaging.

"In the publication, we demonstrated that the synthesis of morphological and functional parameters considerably facilitates the differentiation between tumour types," explains Fabian Kiessling. In the course of their project, they tested the technique in three model cases, including in human subjects. In collaboration with Prof Dr Elmar Stickeler from the Clinic for Gynaecology and Obstetrics at the University Hospital Aachen, the researchers successfully identified how tumour vessels responded to chemotherapy in breast cancer patients.

Monitoring therapy effects

"One reason why this is important is because new therapy approaches aim at manipulating the vascular system of tumours, in order to enhance the therapeutic effect by increasing the concentration of drugs in the tumours," says Fabian Kiessling. One of these approaches is so-called sonoporation. Here, tumours are treated with ultrasound in order to render the vascular walls more permeable to active substances.

"The advantage of our approach is that it can be performed with conventional ultrasound scanners, which have a low frame frequency, with sometimes as few as 15 images per second," points out Georg Schmitz. The research teams have already filed an application for a follow-up project, in the course of which they intend to test the method in large-scale clinical studies.


Journal of the American Society of Echocardiography

Volume 31, Issue 3, March 2018, Pages 289-296

Clinical Use of Ultrasound Enhancing Agents; Contrast-Enhanced Echocardiography Has the Greatest Impact in Patients with Reduced Ejection Fractions

Authors: Hang Zhao MD a, b, Rupal O'Quinn MD a, Marietta Ambrose MD a, Dinesh Jagasia MD a, Bonnie Ky MD a, Joyce Wald DO a, Victor A. Ferrari MD a, James N. Kirkpatrick MD, FASE c, Yuchi Han MD, MMSc, FASE a

aCardiovascular Division, Department of Medicine, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, bDepartment of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China,  cCardiovascular Division, Department of Medicine, University of Washington School of Medicine, Seattle, Washington


•Contrast use in patients with suboptimal images affects patient care, especially in patients who have reduced precontrast estimated LVEF.

•The impact of contrast use is seen more significantly in patients with HF, cardiomyopathy, and arrhythmias.

•The impact of contrast is not influenced by the results of prior studies, whether outpatient or inpatient, or whether the patient has a defibrillator or a pacemaker.


Contrast-enhanced echocardiography (CE) helps to improve image quality in patients with suboptimal acoustic windows. Despite current recommendations, contrast use remains low. The aim of this study was to identify populations that would benefit more from contrast use.


A total of 176 subjects (137 men; mean age, 60.8 ± 13.7 years) with technically difficult transthoracic echocardiographic studies who received clinically indicated intravenous contrast were prospectively studied. The impact on clinical decision making (including alterations in medical therapy, referral, imaging, or clinical procedures) was evaluated.


The use of CE enabled biplane left ventricular (LV) ejection fraction measurement in 97.2% of studies and the interpretation of regional wall motion in 95% of studies. CE allowed definitive assessment of the presence or absence of LV thrombus in 99% of the cases. In the 174 patients whose ordering physicians could be reached at the time of image interpretation, changes in management occurred in 51% of subjects. There was no difference in the proportion of management changes between inpatients and outpatients (60.0% vs 48.1%, P = .225). Subjects with heart failure, cardiomyopathy, and arrhythmia had a higher proportion of changes (61.4% vs 44.2% [P = .031], 62.5% vs 45.0% [P = .028], and 72.0% vs 47.7% [P = .030], respectively). The proportion of management change after CE increased as pre-CE estimated ejection fraction decreased. Logistic regression showed that pre-CE estimated LV ejection fraction < 50% was the only significant predictor of change of management after contrast (P = .004).


The use of CE has a significant impact on clinical decision making in patients with suboptimal acoustic windows, especially in those with depressed pre-CE LV ejection fractions.

ICUS Weekly News Monitor 4-12-2018, Contrast-enhanced subharmonic imaging detects prostate cancers not identified by MRI, April 9, 2018 American Roentgen Ray Society/Press Release

2.AuntMinnie Europe, Fischer: Contrast ultrasound isn't rocket science, April 2, 2018, AIUM: Double dose of US contrast helps find gastric lesions, March 28,By Kate Madden Yee

Contrast-enhanced subharmonic imaging detects prostate cancers not identified by MRI

April 9, 2018

American Roentgen Ray Society/Press release

Study results to be presented at ARRS 2018 Annual Meeting

A test of contrast-enhanced subharmonic imaging (SHI) has shown promise in detecting prostate cancers that were not identified by MRI, according to a study to be presented at the ARRS 2018 Annual Meeting, set for April 22-27 in Washington, DC.

SHI is a new technique for imaging of microbubble ultrasound contrast agents with improved suppression of background tissues. The study to be presented by Venkata Masarapu of Jefferson Medical College of Thomas Jefferson University was conducted to evaluate contrast enhanced SHI of the prostate for detection of prostate cancer.

Among the study group of 28 patients, contrast enhancement was clearly observed with color and power Doppler imaging, as well as with both harmonic imaging (HI) and SHI techniques in all subjects. SHI provided improved contrast signal and tissue suppression relative to conventional HI. Areas of increased vascularity were best delineated with maximum-intensity projection SHI, which allowed visualization of microvascular architecture.

This first in vivo application of contrast-enhanced SHI demonstrated contrast enhancement in the prostate of every study patient, with focal areas of contrast enhancement corresponding to sites of cancer in 18% of targeted biopsies, including five patients whose cancer was not identified by MRI. The results indicate that SHI provides improved conspicuity of microbubble contrast enhancement and may improve the performance of contrast-enhanced ultrasound for detection of prostate cancer.


AuntMinnie Europe

Fischer: Contrast ultrasound isn't rocket science

April 2, 2018

Contrast-enhanced ultrasound (CEUS) has many advantages: It's versatile, well-tolerated by patients, and cost-effective, according to Dr. Thomas Fischer, chair of the ultrasound working group (AGUS) of the German Radiological Society (DRG, Deutsche Röntgengesellschaft) and head of the Interdisciplinary Ultrasound Centre at the Charité Hospital in Berlin. In this interview, he explains the main indications for the technology and how CEUS certification can help increase user acceptance.

Why is contrast-enhanced ultrasound so important for radiologists?

Fischer: The growing role of ultrasound within radiology is closely associated with the development of modern sonographic techniques. One of these, CEUS, is now an essential part of our everyday lives. It gives our patients one of the lowest-risk contrast examinations available, with adverse effects in less than 0.02% of cases. Its diagnostic accuracy for space-occupying lesions of the liver and kidneys is at least comparable with a latest-generation CT scan.

For these reasons, the ultrasound working group wants to increase the role of CEUS in radiology so there's a level playing field with other methods when it comes to making the best possible diagnostic decisions for patients. If you choose ultrasound in a specific situation, you're avoiding radiation exposure and getting a very convincing diagnosis.

Of course MRI is the gold standard in liver diagnostics, for example with the option of a liver-specific contrast medium, and performs slightly better in major comparative studies of diagnostic accuracy. But it's also much more expensive than CT or ultrasound.

If you narrow down the field of application to cases involving a large number of primary benign renal lesions such as focal fatty change, hemangioma, focal nodular hyperplasia, and cysts, major cost-benefit case studies favor CEUS technology even more. But it also takes technical and clinical expertise to use it and achieve a similar quality to other methods.

So far, though, CEUS is not a compulsory part of the radiology continuing education curriculum. Modern ultrasound is the world's most common imaging technique, and there have been a lot of new technical developments so the learning curve is particularly steep. AGUS is holding lectures and practical workshops to address this, and the AGUS board has set up a CEUS certification scheme based on preliminary work by Prof. Teichgräber of Jena.

What are the specific indications for CEUS?

CEUS technology has been evaluated in large diagnostic studies of focal lesions of the liver, and it's proven to be as effective as cross-sectional CT and MRI. Of course, that's only true if the examination of the patient can be easily carried out. So, for example, CT and MRI are better than ultrasound when you're dealing with a massive liver steatosis. It's easy to establish whether this is the case by carrying out a B-scan ultrasound immediately beforehand, and this affects only a small proportion of patients.

As well as this well-known indication, follow-ups after endovascular aortic repair (EVAR) treatment of abdominal aortic aneurysm are playing an increasing part in detecting endoleaks. The advantage is you do a single CT scan after the intervention to assess the condition. You can assess with greater sensitivity and fewer side effects whether the aneurysm sac is shrinking or whether there's an endoleak by using an ultrasound contrast medium, ideally with image fusion technology, which combines the good morphological overview provided by CT and the high spatial resolution of ultrasound.

CEUS can also be used to assess renal cysts just as reliably as with CT. Other new indications include ruling out organ lesions in young, hemodynamically stable patients, and drainage control, for which only three drops of the substance are sufficient to check catheter positioning.

What are the advantages of CEUS compared with other procedures?

They include extremely good tolerance, lack of radiation exposure, and suitability for patients with renal failure or contraindication for MRI. Comparative studies also show that CEUS has a financial advantage: It is simply more cost-effective than CT or MRI for suitable patients. As hospitals come under increasing financial pressure, a problem that is not to be underestimated, radiologists should have access to this method. CEUS is also a safe alternative when you want to avoid repeat examinations, or iodine contrast media are contraindicated, or you can't carry out an MRI because the patient has a pacemaker.

Another big new application is pediatric radiology. It avoids the radiation exposure of CT scans -- radiation damage is much worse in children than in adults -- and you don't have to sedate the patient, whereas you often do with MRI.

However, the contrast medium isn't authorized in Europe yet, like many other products in pediatrics and pediatric radiology, so we're talking about off-label use. The only exception is radiological diagnosis of reflux in children, where voiding cystourethrography has been replaced by contrast ultrasound. Apart from this application, it can already be used in the U.S. to characterize space-occupying renal lesions in children so the European authorities still have some catching up to do compared with the U.S. Food and Drug Administration (FDA).

Does CEUS also have a role to play in interventional ultrasound?

Definitely. I've already mentioned checking drainage position, but CEUS also reduces exposure times in angiography and can be combined with other techniques, for example to confirm the occlusion of an arteriovenous fistula. There are also complex image fusion interventions, such as biopsying the aggressive area of a prostatic carcinoma, or using CEUS to determine the ablation area in the operating room after successful focal therapy of less aggressive prostatic carcinoma.

The quality of ultrasound scans, including CEUS, depends on the user. How do you approach this challenge?

Basically, all examination procedures are user-dependent, and CEUS is no exception. AGUS set up the CEUS training certification to develop the skills of young radiologists, and to improve competence within further education and training institutions in this specialist ultrasound technique. We've deliberately made the certification process straightforward to show how simple, innovative, and effective this method is. Young radiologists can already get the CEUS certification as part of the diagnostic radiologist training, provided they're members of the DRG.

A good example is training young emergency room colleagues in focused assessment with sonography for trauma (FAST) ultrasound. Here again, a contrast medium is used, so it's fairly easy to check for spleen and kidney damage in hemodynamically stable accident patients. We're holding FAST ultrasound workshops, each lasting a few days, four times a year. These are combined with supervised practical use of the method.

Radiology centers of excellence are also getting CEUS certification. What's happening there?

The training plan involves a two-day tested interactive CEUS workshop run by AGUS, and participants also sit in on at least two CEUS examinations at a center of excellence of their choice. They get the certification when they've provided proof of attendance. We plan to hold at least one workshop a year on the principles and clinical applications of CEUS. To make it as practical as possible, participants will deal with interactive and tablet-based clinical case studies.

The applications used in the workshop are based on the current CEUS guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). Apart from the basics of CEUS, they'll also deal with applications, for example in the liver, trauma, interventions, and pediatric cases. We want the certificate to dispel any misconceptions and show that CEUS isn't witchcraft. Once you've carried out the procedure a few times under supervision, it's an important addition to the range of your radiological skills. And ultrasound specialists have a long-term future: They can't easily be replaced by a computer.

Are you planning to expand the certification in future, for example by holding events at the Radiology Congress or involving more centers of excellence?

This year's interactive CEUS workshop will take place in Munich, and we'll be announcing the date on the AGUS website. We're looking at whether the format can be transferred to the Radiology Congress. Basically, AGUS would welcome there being more CEUS centers across the country to be able to provide comprehensive training. Therefore we're pleased that more CEUS placements are being offered in hospital radiology departments and practices. They have to carry out at least a hundred CEUS examinations a year as part of their clinical routine in at least one area of application, and the numbers of examinations have to be formally confirmed by the head physician or center manager.

Editor's note: This is an edited version of a translation of an article published in German online by the DRG. Translation by Syntacta Translation & Interpreting. To read the original article, go to:


AIUM: Double dose of US contrast helps find gastric lesions

March 28, 2018

By Kate Madden Yee,AuntMinnie.comstaff writer

Giving a double dose of ultrasound contrast in the form of both oral and injectable agents improves the modality's diagnostic performance for characterizing gastric lesions, according to research presented at the American Institute of Ultrasound in Medicine (AIUM) meeting.

The technique, which Chinese researchers have dubbed double-contrast enhanced ultrasound (DCUS), combines CEUS enhancement characteristics with quantitative perfusion. It shows promise as a tool for distinguishing gastric cancer and gastrointestinal stromal tumors (GISTs) from benign lesions.

"[DCUS] uses an oral contrast agent to displace air, which produces distention and allows for clearer visualization of the multilayered echo pattern of the gastric wall," said presenter Dr. Man Lu, PhD, of the University of Electronic Science and Technology of China in Chengdu.

Benign from malignant

Gastrointestinal endoscopy and endoscopic ultrasound are the traditional methods used for evaluating gastric lesions, Lu said. The drawbacks of these techniques are that they are invasive. Conventional ultrasound might seem like a good solution, but it doesn't easily visualize these lesions. That's where contrast ultrasound comes in.

"CEUS offers real-time perfusion and provides vascular characterization of lesions or organs of interest," she said.

But Lu and colleagues wondered if adding DCUS could further improve the performance of CEUS in the task of characterizing gastric lesions. DCUS involves patients taking an oral contrast agent, which causes the ultrasound lumen to appear as a homogenous acoustic window, according to Lu. The patients are then given a second contrast dose, this time of an injectable agent.

The study included 107 patients with pathology-confirmed gastric lesions who underwent both DCUS and regular CEUS before surgery. The researchers analyzed a variety of perfusion parameters, including contrast arrival time, peak intensity, time to peak, and area under the curve (AUC) of the lesion and surrounding normal tissue. A reader blinded to pathology results rated and compared each case with surgical or resection biopsy pathology results.

Out of 107 gastric lesions, 75 were malignant (33 cancers and 42 GISTs) and 32 were benign (11 inflammatory masses and 21 polypoid adenomas).

Compared with regular CEUS, DCUS performed better across a range of measures, Lu said.

Comparison of CEUS and DCUS in characterizing gastric lesions










Positive predictive value



Negative predictive value



Overall accuracy



Lu's team also found that malignant lesions had faster contrast arrival time and higher peak intensity and AUC than normal tissue in the DCUS exams. In addition, GIST and inflammatory masses had higher peak intensity than normal tissue.

Other results from the DCUS exams were as follows:

•Gastric cancers and GISTs had faster arrival time than polypoid adenomas.

•Inflammatory masses showed higher peak intensity than the other types of lesions.

•Gastric cancers had higher peak intensity than polypoid adenomas and GISTs.

•Gastric cancers and inflammatory masses had a larger area under the curve than polypoid adenomas and GISTs.

Adding DCUS to CEUS appears to overcome conventional ultrasound's limitations in characterizing gastric lesions, Lu said.

"DCUS improved diagnostic performance compared with [CEUS alone] and may be a useful method for evaluating the blood supply of gastric lesions to distinguish between those that are benign and those that are malignant," she concluded.

ICUS Weekly News Monitor 4-4-2018

1.  ICUS, CEUS Basic Training, Chicago Apr 21/22

2.  ILCA,  Mar 20, 2018,  Message from the ILCA President

3.  Ultrasound in Medicine and Biology,  Jan 29, 2018,  Meta-Analysis: Contrast Enhanced Ultrasound versus conventional Ultrasound for differentiation of benign and malignant breast lesions     Authors:  Qian Li, et al

CEUS "Basic Training"


ICUS is proud to expand its educational programs in 2018 to include practical training for successful use of contrast enhanced ultrasound (CEUS) of the cardiovascular system and abdomen.

Learn when and how to use CEUS to improve patient care, outcomes and workflows.


Chicago - April 21-22, 2018

Cardiac CEUS

 Saturday, April 21 - Willis Tower, Suite 5900, Chicago, IL 60606 

Steve Feinstein, MD- Professor, Rush University Medical Center; Program Host
Thomas Porter, MD- Chair of Cardiology, University of Nebraska
Joseph Petrusa, RDCS- Manager, Rush Echocardiology Laboratory
John Grabowski, BSN, RN- Nursing Supervisor, Rush Echocardiology Laboratory 

Abdominal CEUS

 Sunday, April 22 - Willis Tower, Suite 5900, Chicago, IL 60606 

Speaker: Richard Barr, MD, PhD 
Professor of Medicine, Northeast Ohio Medical University
Host: Stephanie Wilson, MD
Professor of Medicine, University of Calgary  


A $100 registration fee per training program includes program materials and meals.  Registration does not include transportation or lodging, which should be arranged by participants themselves. 

Students and trainees will receive a $50 refund after showing appropriate ID when checking in for the program. 

Online registration links: 

Program Description

To see full agendas and course descriptions, go  

Expert lectures will address practical skills needed to implement a successful CEUS program, with multiple ultrasound systems and contrast agents available for participants to examine. Topics will include: 

  1. Microbubble contrast agents: Safety, uses, cost effectiveness. 
  2. Getting started: From set-up to injection to optimizing settings and performance.  
  3. Interpreting the images: Basic and advanced skills.
  4. CEUS economics:What you need to know about billing codes, and using CEUS to reduce the length of hospital stays and time to diagnosis. 
  5. Knobology– Break out rooms with personalized opportunities to "touch and feel" multiple ultrasound systems and contrast agents, examine settings, etc. 

Programs are suitable for physicians, sonographers, nurses, technicians, administrators, industry and others interested in CEUS. 


Dentons US LLP
Willis Tower - 233 S Wacker Dr #5900, Chicago, IL 60606

*Use entrance on Adams Street.

Note: Classes will start promptly at 8am; to ensure on-time arrival, attendees should allow extra time for security and building navigation.

For additional information, please contact:

Stephanie Wilson, MD - This email address is being protected from spambots. You need JavaScript enabled to view it. This email address is being protected from spambots. You need JavaScript enabled to view it. , Steve Feinstein, MD -  This email address is being protected from spambots. You need JavaScript enabled to view it.


International Liver Cancer Association (ILCA)

Message from the ILCA President

Mar 20, 2018

Dear colleagues,

Worldwide interest in HCC continues to grow. In 2017 Pubmed recorded over 7000 articles in which HCC was a keyword. Of these about 10% were reviews. Of course, some of these publications were in low impact journals and would not be expected to change practice in any meaningful way. However, there was at last one major clinical advance, with positive results coming from the cabozantinib trial. There are now 5 agents that are either licensed or will be, that can be used for the management of HCC. The big question will be whether these agents can be combined and if so how should they be combined or used sequentially. On the basic science side, there were many articles exploring the genetics of HCC and the expression profile of these cancers. The tumour (and liver) microenvironment was also the subject of intensive investigation.

Non-alcoholic fatty liver disease has a complex relationship with hepatocellular carcinoma. Many investigators, both in the laboratory and in the clinic are trying to get to grips with these complexities to understand how fatty liver predisposes to HCC, and from a clinical standpoint, how to define who is at risk for HCC and how to provide surveillance. New surveillance algorithms that do not necessarily include ultrasonography are required.

Contrast ultrasound agents are now available in the USA, bringing ultrasound in the US into the 21st century. It is a mystery that contrast US has been widely available elsewhere for years, but only recently in the US. In response the LI-RADS group has developed specific reporting tools for liver masses interrogated by contrast ultrasound.

At ILCA, the Executive Committee is exploring new ways to improve our “product”, to provide more services to our members and to the liver cancer community in general. More on this in future columns as these projects move to fruition.

Best wishes and regards to all,

Morris Sherman


Ultrasound in Medicine and Biology

Meta-Analysis: Contrast Enhanced Ultrasound versus conventional Ultrasound for differentiation of benign and malignant breast lesions.

Jan 29, 2018

Vol. 44, No. 5, pp. 919–929, 2018

Authors: Qian Li,* Min Hu,† Zhikui Chen,‡ Changtian Li,§ Xi Zhang,¶ Yiqing Song,‖ and Feixiang Xiang**,††

* Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; † Department of Cardiovascular Surgery, Tongji Hospitial, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, China; ‡ Department of Ultrasound, Union Hospital, Fujian Medical University, Fuzhou, Fujian, China; § Department of Ultrasound, The Southern Building, Chinese PLA General Hospital, Beijing, China; ¶ Clinical Research Unit, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; ‖ Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA; ** Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue,Wuhan 430022, China; and †† Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, 1277 JieFang Avenue,Wuhan 430022, China


This meta-analysis aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS), conventional ultrasound (US) combined with CEUS (US + CEUS) and US for distinguishing breast lesions. From thorough literature research, studies that compared the diagnostic performance of CEUS versus US or US + CEUS versus US, using pathology results as the gold standard, were included. Atotal of 10 studies were included, of which 9 compared the diagnostic performance of CEUS and US, and 5 studies compared US + CEUS and US. In those comparing CEUS versus US, the pooled sensitivity was 0.93 (95% CI: 0.91–0.95) versus 0.87 (95% CI: 0.85–0.90) and pooled specificity was 0.86 (95% CI: 0.84–0.88) versus 0.72 (95% CI: 0.69–0.75). In studies comparing US + CEUS versus US, the pooled sensitivity was 0.94 (95% CI: 0.92–0.96) versus 0.87 (95% CI: 0.84–0.90) and pooled specificity was 0.86 (95% CI: 0.82–0.89) versus 0.80 (95% CI: 0.76–0.84). In terms of diagnosing breast malignancy, areas under the curve of the summary receiver operating characteristic (of both CEUS (p = 0.003) and US + CEUS (p = 0.000) were statistically higher than that of US. Both CEUS alone and US + CEUS had better diagnostic performance than US in differentiation of breast lesions, and US + CEUS also had low negative likelihood ratio.


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