ICUS Weekly News Monitor 3-22-2018

  1. Dove Press, Ultrasound molecular imaging of breast cancer in MCF-7 orthotopic mice using gold nanoshelled poly(lactic-co-glycolic acid) nanocapsules: a novel dual-targeted ultrasound contrast agent, March 21, 2018 Authors: Li Xu, et al
  2. Uro Today, EAU 2018: Prostate Cancer Diagnosis by Three-Dimensional Contrast-Ultrasound Dispersion Imaging, March 2018 Presented by: Massimo Mischi, MD, et al.
  3. Journal of Kidney Cancer and VHL, Contrast-Enhanced Ultrasound-Guided Radiofrequency Ablation of Renal Tumors, Feb, 2018 Authors: Dan O’Neal, et al
  4. Echo Research and Practice, Discounted open access publishing


Dove Press

Ultrasound molecular imaging of breast cancer in MCF-7 orthotopic mice using gold nanoshelled poly(lactic-co-glycolic acid) nanocapsules: a novel dual-targeted ultrasound contrast agent

March 21, 2018

Authors: Li Xu,1,* Jing Du,1,* Caifeng Wan,1 Yu Zhang,1 Shaowei Xie,1 Hongli Li,1 Hong Yang,2 Fenghua Li1

1Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; 2Department of Chemistry, College of Life and Environmental Science, Shanghai Normal University, Shanghai, China

*These authors contributed equally to this work

Published 21 March 2018 Volume 2018:13 Pages 1791—1807

  1. DOI


Background: The development of nanoscale molecularly targeted ultrasound contrast agents (UCAs) with high affinity and specificity is critical for ultrasound molecular imaging in the early detection of breast cancer.

Purpose: To prospectively evaluate ultrasound molecular imaging with dual-targeted gold nanoshelled poly(lactide-co-glycolic acid) nanocapsules carrying vascular endothelial growth factor receptor type 2 (VEGFR2) and p53 antibodies (DNCs) in MCF-7 orthotopic mice model.

Methods: DNCs were fabricated with an inner PLGA and outer gold nanoshell spherical structure. Its targeting capabilities were evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) in vitro. Contrast-enhanced ultrasound imaging (CEUS) with DNCs was evaluated qualitatively and quantitatively in vitro and in MCF-7 orthotopic mice model by two different systems. The biodistribution of NCs in mice was preliminary investigated. Differences were calculated by using analysis of variance.

Results: DNCs showed a well-defined spherical morphology with an average diameter of 276.90±110.50 nm. In vitro, DNCs exhibited high target specificities (79.01±5.63% vs. 2.11±1.07%, P<0.01; 75.54±6.58% vs. 5.21±3.12%, P<0.01) in VEGFR2- and p53-positive cells compared with control cells. In vivo, CEUS displayed a significantly higher video intensity in two systems using DNCs in comparison with non-targeted PLGA@Au NCs and single-targeted NCs. Biodistribution studies revealed that more DNCs in breast cancer tissue could be detected in mice than in other NCs (P<0.05).

Conclusion: DNCs were demonstrated to be novel dual-targeted UCAs and may have potential applications in early non-invasive visualization of breast cancer.


Uro Today

EAU 2018: Prostate Cancer Diagnosis by Three-Dimensional Contrast-Ultrasound Dispersion Imaging

March 2018

Presented by: Massimo Mischi, MD Eindhoven University of Technology, Eindhoven, The Netherlands

Co-Authors: Schalk S, Huang J, Li J, Wijkstra H, Huang P

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, twitter: @zklaassen_md at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark

Dr. Mischi and colleagues presented results of their experience using 3-D contrast ultrasound dispersion imaging. Dynamic contrast-enhanced ultrasound (DCE-US) provides the opportunity to localize prostate cancer by detection of an associated angiogenic processes. As such, dedicated DCE-US methods have been proposed, however until now these methods have been validated in 2D only, requiring the injection of an ultrasound contrast agent bolus for the analysis of each imaging plane. The need for multiple injections hampers the value of these methods for routine clinical practice. A 3D approach would overcome this problem and the full prostate volume could be analyzed by injection of a single ultrasound contrast agent bolus. The objective of this study was to investigate the feasibility of 3D contrast-ultrasound dispersion imaging for prostate cancer localization.

There were 43 patients referred for 12-core systematic biopsy who underwent 3D DCE-US. For each recording, parametric maps of dispersion and standard perfusion parameters were computed.

Three dimensional contrast ultrasound dispersion imaging

Per biopsy core, the presence of malignancy and the Gleason score were reported. Each prostate was divided in 12 sections corresponding to the biopsy locations. The 90th percentile values of the parameters in each section were compared with the corresponding biopsy outcome. Sections were considered malignant when at least half of the biopsy cores were malignant; sensitivity and specificity to prostate cancer were also evaluated.

Contrast ultrasound dispersion imaging results were superior to standard perfusion parameters. Significant difference between sections corresponding to benign and malignant biopsy cores (p<0.001) was observed. The area under the receiver operating characteristic curve strongly increased for sections consisting of ≥50% malignant cores. In a left/right analysis, sensitivity and specificity were 65% and 80%; in a per-prostate analysis, they were 94% and 50%.

The authors concluded that based on this study, quantitative 3D DCE-US by dispersion imaging can detect prostate cancer. Furthermore, a 3D approach enables the investigation of the full prostate by a single contrast bolus injection, facilitating the clinical utilization of the method. However, Dr. Mischi and colleagues recommend additional, improved validation by comparison with the histopathological analysis of corresponding radical-prostatectomy specimens.


Journal of Kidney Cancer and VHL

Contrast-Enhanced Ultrasound-Guided Radiofrequency Ablation of Renal Tumors

February, 2018

Authors: Dan O’Neal1, Tal Cohen1, Cynthia Peterson2,3, Richard G. Barr1,3

1Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio, USA; 2Kent State University, Salem, OH, USA; 3Ultrasound Training, Southwoods Imaging, Youngstown, OH, USA


Although only limited long-term studies evaluating thermal ablation of renal masses have been performed, it appears that thermal ablation has a comparable 5-year success rate to that of partial or total nephrectomy. This technique is often used in patients who are not good candidates for partial or total nephrectomy. Contrast-enhanced ultrasound (CEUS) has been recently approved by the Food and Drug Administration for characterization of focal liver lesions in adults and pediatric patients. CEUS can be used off label for renal applications and has been used for years in Europe and Asia. It has several advantages over contrast-enhanced computed tomography for use as the technique to guide and evaluate efficacy of thermal ablation of renal masses. These include the ability to visualize small amounts of enhancement, repeat dosing to evaluate efficacy of an ablation during a procedure, thin slice thickness, and real-time visualization. Ultrasound contrast is also non-nephrotoxic and non-hepatotoxic, allowing evaluation of patients with renal insufficiency. This article reviews the use of CEUS for the guidance and follow-up of thermal ablative procedures of renal masses.

Author for correspondence: Richard G. Barr, Northeastern Ohio Medical University, Southwoods Imaging, 7623 Market Street, Youngstown, OH 44512, USA. Email: 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.

How to cite: O’Neal D et al. Contrast-enhanced ultrasound-guided radiofrequency ablation of renal tumors. J Kidney Cancer VHL 2018; 5(1):7–14. DOI:

Copyright: O’Neal D et al.


Echo Research and Practice

Discounted open access publishing

Echo Research and Practiceis an open-access journal dedicated to publishing the latest research on echocardiography and its associated imaging modalities.  ICUS members are entitled to a 25% discount on the open-access publishing charge. The journal is indexed in Scopus, PubMed and the Web of Science’s Emerging Sources Citation Index.

Find out more at:  

ICUS Weekly News Monitor 12-21-2017

  1. ICUS,  Dec 15, 2017,  GE Healthcare - Imagination at Work: A powerful innovation in liver imaging (Extract)
  2. Journal of the American Society of Echocardiography,  Oct 17, 2017,  Right Ventricular Size and Function; Quantification of Right Ventricular Size and Function from Contrast-Enhanced by Three-Dimensional Echocardiographic Images

Authors:  Diego Medvedofsky, MD, et al.

GE Healthcare - Imagination at Work: A powerful innovation in liver imaging

Dec 15, 2017

(Extract. Courtesy of GE Healthcare. Reproduced with permission.)

Contrast-enhanced ultrasound is a valuable and affordable diagnostic tool for assessing liver lesions. It is also easy to adopt as a service with minimal investment in equipment and training. Clinician education and more clarity around procedure reimbursement are keys to its wider adoption for patients’ benefit.

Advantages of CEUS

Microbubble contrast agents have greatly expanded the utility of ultrasound in the liver, especially for evaluating liver lesions. Contrast-enhanced ultrasound (CEUS) is emerging as a quick and low-risk technique that in a variety of cases can provide a lower-cost, more immediately available alternative to CT and MR contrast exams.

CEUS exams are fast and often definitive. They may also have significant value for patients who are at risk from nephrotoxic contrast agents.

Furthermore, CEUS is relatively simple to add as a service – it requires no substantial capital investment and only a minimum of staff training. The basic steps to CEUS adoption are simple and straightforward as outlined below.

Clinician education is a key to the technique’s growth: many specialists are unaware of it or do not appreciate its full range of capabilities. It is also important to resolve issues surrounding reimbursement for the contrast portion of the procedure and to ensure that CEUS is included in decision-support software tools that help clinicians gauge the appropriateness of imaging studies.

CEUS has the built-in advantage of enabling clinicians to assess contrast enhancement patterns in real time, with better temporal resolution than other modalities. Ultrasound microbubble contrast agents allow lesion enhancement to be observed in all vascular phases in real-time imaging. Side effects from  these agents are very rare. They can be given without first assessing liver or kidney function and, if need be, multiple doses can be given repeatedly in the same imaging session.1

Among the compelling clinical benefits, a CEUS exam:

  • Costs less than MR and CT scans.
  • Avoids the radiation exposure of a CT study.
  • Saves time: A CEUS study takes approximately 10 minutes after the IV is placed and contrast given, versus 45 minutes or more inside an MR scanner bore.
  • Eliminates the challenge inherent in MR scans for claustrophobic patients, and for those who are otherwise unable to tolerate a lengthy exam and may require sedation.

In the liver, CEUS can be used to define and characterize lesions. It can help definitively distinguish benign from malignant lesions; no confirmation with CT or MR is needed. In patients at risk for hepatocellular carcinoma (HCC), liver monitoring via ultrasound is performed at intervals, such as every six months. If a lesion is observed, CEUS can be arranged on the spot and the patient can receive a diagnosis before leaving the clinic.

After treatment of a tumor, CEUS can be used to determine whether any viable malignant tissue remains. Patients can be monitored over time to ensure against recurrence. In these cases, CT or MR follow-ups may be necessary to look for new tum or elsewhere in the liver.

In view of these benefits, many care centers are exploring the addition of CEUS. Here is an overview of the basic steps involved:

Step 1: Adding ultrasound contrast agents to the formulary

CEUS procedures have been simplified by the emergence of a contrast agent FDA-approved in April 2016 for characterization of focal liver lesions in adult and pediatric patients. This agent was previously FDA-approved for use in adults with suboptimal echocardiograms to opacify the left ventricular chamber and improve delineation of the left ventricular endocardial border.

Lumason is now FDA-approved for use in liver imaging to improve the sensitivity and specificity of ultrasonography in differentiating between malignant and benign focal hepatic lesions. It is the first ultrasound contrast agent approved for use in pediatric patients.

There are generally no major issues in getting a contrast agent added to the formulary. While approval procedures differ among hospitals, here are a few essential steps to follow:

  • Work with your institution’s pharmacy committee to identify the steps to add a new drug to the formulary. If a CEUS contrast agent is already present, you may need to provide justification for a second one.
  • Complete an application for decision-makers that emphasizes:
    • The agent’s clinical value and patient safety profile.
    • The agent’s workflow benefits and FDA approval.
  • If there are issues, consult with external sources, including the contrast agent manufacturer, to identify the appropriate approval channels.

Step 2: Training the staff

An essential component of CEUS is training staff to perform the procedure and having access to personnel qualified to start the necessary IV.

The level of sonographers’ involvement in CEUS studies will vary by institution. Some physicians prefer to conduct the actual scans themselves; in those cases the sonographers may perform pre-injection images and position the patients for the exams.

Others train sonographers in the scanning procedure. As CEUS gains acceptance and procedure volumes grow, there are different options for managing IV cannulation. In some centers, nurses start the IVs. In other cases, MR or CT technologists do so. Institutions with higher CEUS volumes train sonographers for this role. The question is which model works best given the patient load and availability of qualified staff.

Step 3: Scheduling CEUS cases

Ease of scheduling adds to the benefits of CEUS. Typically, the exams are scheduled as outpatient procedures, on relatively short lead times. Referring physicians should be instructed to specify  ultrasound contrast on their orders. Where this does not occur, the radiologist needs to call the referring physician back and have the contrast instruction added.

There are two basic models for scheduling cases. The first is to pre-schedule patients, reserving a day or an afternoon for contrast cases. This has the advantage of ensuring that CEUS champions and IV placement personnel are available on site. On the other hand, it may forfeit the opportunity to perform  cases on the spot where warranted.

In the second model, the department allows add-on CEUS studies. For example, when a suspicious liver lesion is detected in a new patient, a physician can order and perform a CEUS exam on the same day, instead of waiting days or weeks for a CT or MRI appointment. An advantage of the same-day “add-on” CEUS study is that it avoids the risk of the patient failing to show up for a second appointment. More important, CEUS can immediately rule out malignancies, or confirm them so that the referring physicians can be notified and the patients’ care expedited.

Generally speaking, CEUS practices start with pre-scheduled exams and move up to performing add-on cases as volume grows and the staff becomes comfortable with the procedure.

Step 4: Educating clinicians

Education about CEUS and its clinical value is vital to its wider acceptance. For example, some radiologists may need to be shown evidence that CEUS has clinical value, poses minimal risk to patients, and will not consume more of their limited time. In addition, before embarking on a CEUS practice, it is essential to make presentations to the clinical teams that comprise the main sources of referrals: hepatologists for patients with liver masses, oncologists for patients with cancer. Presentations need to demonstrate the benefits of CEUS to clinical practice.

Remember to educate your Department leaders who should not  be overlooked in education; the better they understand the benefits of CEUS, the more likely they will be to approve its use. Practitioners should seek hands-on clinical experience. Ways to do so include visiting an existing center with a CEUS practice to observe cases, identifying and consulting with a few goto experts, and working with ultrasound vendors to evaluate imaging systems and view technology demonstrations.

Billing and reimbursement

While a CPT code exists for the contrast agent itself, no such code yet exists for the professional component of the contrast portion of the ultrasound exam. For hospitals serving indigent patients, CEUS enables savings because the exams cost significantly less than CT or MRI. Otherwise, uncertainty about reimbursement gives some physicians pause.

With wider adoption, CEUS promises to bring new excitement and potentially game-changing benefits to a long standing, tried-and-true liver imaging technology. It can reinforce ultrasound as a robust imaging modality.

Adding CEUS: Tips to smooth the process

It is not difficult to add contrast-enhanced ultrasound as a technique for evaluating liver lesions. Here are a few ideas for helping the process ramp up smoothly.

  • Identify current IV placement resources and utilize their expertise when possible.
  • Identify a few enthusiastic sonographers to train in the CEUS technique. They are likely to find it invigorating to learn about a new and powerful ultrasound procedure.
  • Identify one or two radiologists to champion CEUS and drive implementation.
  • Educate referring physicians on the clinical benefits of CEUS for evaluating liver lesions and instruct them to add it as an option on their orders.


  1. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver – update 2012 AWFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS AND ICUS. Ultrasound in Med. & Biol., Vol. 39, No. 2, pp. 187–210, 2013. ©2013 World Federation for Ultrasound in Medicine & Biology.

Imagination at work may not be available in all countries and regions. Contact a GE Healthcare Representative for more information.

Data subject to change.

© 2017 General Electric Company . February 2017/JB46265US

GE, the GE Monogram and imagination at work are trademarks of General Electric Company.

Reproduction in any form is forbidden without prior written permission from GE. Nothing in this material should be used to diagnose or treat any disease or condition. Readers must consult a healthcare professional.


Journal of the American Society of Echocardiography

J Am Soc Echocardiogr 2017;30:1193-202

Oct 17, 2017

Right ventricular Size and Function

Quantification of Right Ventricular Size and Function from Contrast-Enhanced Three-Dimensional Echocardiographic Images

Authors:  Diego Medvedofsky, MD, Victor Mor-Avi, PhD, Eric Kruse, RDCS, Brittney Guile, RDCS Boguslawa Ciszek, RDCS, Lynn Weinert, RDCS, Megan Yamat, RDCS, Valentina Volpato, MD, Karima Addetia, MD, Amit R. Patel, MD, and Roberto M. Lang, MD, Chicago, Illinois


  • We hypothesized that contrast enhancement during 3D echocardiographic imaging would improve the accuracy of RV volume and function analysis.
  • This hypothesis was tested by comparing measurements obtained from nonenhanced and contrast-enhanced images against cardiac magnetic resonance reference images.
  • Contrast enhancement improved the visualization of RV endocardial borders, resulting in more accurate and more reproducible measurements.
  • This approach may be particularly useful in patients with suboptimal image quality.


Three-dimensional (3D) echocardiography directly assesses right ventricular (RV) volumes without geometric assumptions, despite the complex shape of the right ventricle, and accordingly is more accurate and reproducible than the two-dimensional methodology, which is able to measure only surrogate parameters of RV function. Volumetric analysis has been hampered by frequent inability to clearly visualize RV endocardium, especially the RV free wall, in 3D echocardiographic images. The aim of this study was to test the hypothesis that RV contrast enhancement during 3D echocardiographic imaging would improve the accuracy of RV volume and function analysis.


Thirty patients with a wide range of RV size and function and image quality underwent transthoracic 3D echocardiography with and without contrast enhancement and cardiovascular magnetic resonance imaging on the same day. RV end-diastolic and end-systolic volumes and ejection fraction were measured from contrast-enhanced and nonenhanced 3D echocardiographic images and compared with cardiovascular magnetic resonance reference values using linear regression and Bland-Altman analyses. Blinded repeated measurements were performed to assess measurement variability.


RV contrast enhancement was feasible in all patients. RV volumes obtained both with and without contrast enhancement correlated highly with cardiovascular magnetic resonance (end-diastolic volume, r = 0.90 and r = 0.92; end-systolic volume, r = 0.92 and r = 0.94, respectively), but the correlation for ejection fraction was better with contrast (r = 0.87 vs r = 0.70). Biases were smaller with contrast for all three parameters (end-diastolic volume, −16 ± 23 vs −36 ± 25 mL; end-systolic volume, −10 ± 16 vs −23 ± 18 mL; ejection fraction, −0.7 ± 5.5% vs −2.7 ± 8.1% of the mean measured values), reflecting improved accuracy. Also, measurement reproducibility was improved by contrast enhancement.


Contrast enhancement improves the visualization of RV endocardial borders, resulting in more accurate and reproducible 3D echocardiographic measurements of RV size and function. This approach may be particularly useful in patients with suboptimal image quality.

ICUS Weekly News Monitor 12-1-2017

Journal of the American Society of Echocardiography

Contrast-Enhanced Echocardiography Has the Greatest Impact in Patients with Reduced Ejection Fractions.

Oct 27, 2017

Authors:  Zhao H, et al.

J Am Soc Echocardiogr. 2017.
Citation: yuchi


BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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. 


Journal of Hepatology

Contrast enhanced ultrasound identifies hepatocellular carcinoma in cirrhosis: a large multicenter retrospective study.

Nov 10, 2017

pii: S0168-8278(17)32428-5doi:10.1016/j.jhep.2017.11.007.

PMID: 29133247

Authors: Terzi E(1), Iavarone M(2), Pompili M(3), Veronese L(4), Cabibbo G(5), Fraquelli M(6), Riccardi L(3), De Bonis L(1), Sangiovanni A(2), Leoni S(1), Zocco MA(3),Rossi S(4), Alessi N(5), Wilson SR(7), Piscaglia F(8),

Collaborators: Granito A(1), Salvatore V(1), Tovoli F(1), Manini MA(2), Rapaccini GL(3), Ainora ME(3), Ravetta V(4), Ghittoni G(4), Ventra A(5), Mogavero G(5).

Author information:

(1)Department of Medical and Surgical Sciences, Division of Internal Medicine, Sant'Orsola-Malpighi Hospital, University of  Bologna, Bologna, Italy.

(2)A.M. & A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University ofMilan, Milan, Italy.

(3)Internal Medicine, Gastroenterology and Hepatology, Gemelli Hospital, University of Rome, Rome, Italy.

(4)Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.

(5)Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy.

(6)Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy.

(7)Radiology and Medicine, Division of Gastroenterology, University of Calgary, Canada.

(8)Department of Medical and Surgical Sciences, Division of Internal Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. Electronic address:   This email address is being protected from spambots. You need JavaScript enabled to view it. .

BACKGROUND & AIMS: The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned for therisk of false positive diagnosis in case of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS LI-RADS) classifying lesions at risk for HCC investigated by CEUS. Aim of the present study was tovalidate this LI-RADS scheme for the diagnosis of HCC.

METHODS: A total of 1006 nodules in 848 patients with chronic liver disease at risk for HCC collected in 5 Italian centers were retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥ 1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 seconds after contrast injection)of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4).Diagnostic reference standard was CT/MRI diagnosis of HCC (=506) or histology (n=500).

RESULTS: Median size was 2 cm. Of 1006 nodules, HCC were 820 (81%), cholangiocarcinoma 40 (4%), regenerative nodules (±dysplastic) 116 (11%). TheLR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC96=47%) and the LR-4 202 (HCC 173=87%).

CONCLUSIONS: The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non invasive diagnosis. LAY SUMMARY A retrospective study of approximately 1000 focal lesions at risk for HCC, demonstrates that the refined definition of the typical contrast enhanced ultrasound pattern of hepatocellular carcinoma (HCC) introduced by the Liver Imaging Reporting and Data System (LI RADS) practically abolishes the risk of misdiagnosis of other malignant entities (e.g. cholangiocellular carcinoma) for HCC with negligible reduction in sensitivity. These data support the use of contrast enhanced ultrasound todiagnose hepatocellular carcinoma in cirrhosis.

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