ICUS Weekly News Monitor 9-16-2016

1.  American College of Radiology,  Sep 1, 2016,  ACR CEUS LI-RADS 2016 - The ACR announces the official release of CEUS LI-RADS.
2.  International Contrast Ultrasound Society (ICUS),  Sep 9, 2016,  Contrast Ultrasound Identifies Deadly Liver Cancers     (Business Wire)
3.  International Contrast Ultrasound Society (ICUS),  Sep 8, 2016,  CEUS Liver and Kidney  Tests Produce Big Savings in Testing Time and Cost     (Business Wire)
*To view presentations live-streamed from the 31st Annual Advances in Contrast Ultrasound Bubble Conference held in Chicago, 8/9 September 2016, go to:
American College of Radiology
Sep 1, 2016
The ACR announces the official release of CEUS LI-RADS.
ACR CEUS LI-RADS, or CEUS LI-RADS for short, is a standardized system for technique, interpretation, reporting, and data collection for contrast-enhanced ultrasound (CEUS) exams in patients at risk for developing HCC. The system currently includes a lexicon of controlled terminology, schematic illustrations, and a categorization algorithm. A complete illustrative atlas, reporting guidelines, and educational material are in development. CEUS LI-RADS will be updated as experience accrues, as knowledge add technology advance, and in response to user feedback.
ACR CEUS LI-RADS was developed by working group of national and international experts. The group is Chaired by Dr. Yuko Kono, MD, of the University of California, San Diego. Members include radiologists and hepatologists from the United States, Canada, Europe, and Asia. The group was convened in April 2014. Beta versions of the CEUS LI-RADS algorithm were presented at national and international conferences in 2015 and 2016. Feedback was solicited. Based on the feedback and iterative consensus, the working group refined and in 5-21-16 finalized the CEUS LI-RADS algorithm. The algorithm was officially approved by the ACR LI-RADS Steering Committee on 6-24-16 and submitted to the ACR for public release on 6-24-16.
Please click here to view the complete CEUS LI-RADS 2016 Presentation »
International Contrast Ultrasound Society (ICUS)
Sep 9, 2016
Contrast Ultrasound Identifies Deadly Liver Cancers
CHICAGO -- (Business Wire) -- Tiny microbubbles are being used to more effectively identify liver tumors, according to a study described today at the 31st annual Advances in Contrast Ultrasound conference in Chicago.
Patients with hepatocellular carcinoma, the third leading cause of cancer deaths worldwide, were found to benefit from contrast-enhanced ultrasound (CEUS) imaging when MRI imaging was inconclusive, according to Dr. Stephanie Wilson, a professor of medicine at the University of Calgary in Canada and Co-President of the International Contrast Ultrasound Society.   She said that inconclusive MRIs occur frequently.
"This is an exciting option because hepatocellular carcinoma is the most common form of liver cancer, and standard imaging with MRI is often an insufficient option for characterizing the tumor," Dr .Wilson said.
CEUS uses liquid suspensions of tiny gas microbubbles  to improve the clarity and reliability of an ultrasound image without exposing patients to ionizing radiation.  The microbubbles are smaller than red blood cells and, when they are injected into a patient's arm vein, they improve the accuracy of diagnostic ultrasound exams. The microbubbles are expelled from the body within minutes.
David Cosgrove, Emeritus Professor at Imperial and Kings Colleges London, said the findings demonstrate the vast potential benefits of using microbubble ultrasound contrast agents as a safe, convenient and effective diagnostic imaging tool that improves patient care without exposing individuals to ionizing radiation. "CEUS is an excellent modality that can help differentiate benign from malignant tumors," he added.
*View the original presentation delivered by Dr Stephanie Wilson at the 31st Annual Advances in Contrast Ultrasound Bubble Conference by going to:
International Contrast Ultrasound Society (ICUS)
Sep 8, 2016
CEUS Liver and Kidney  Tests Produce Big Savings in Testing Time and Cost
CHICAGO -- (Business Wire) - Contrast-enhanced ultrasound (CEUS) can speed up the diagnosis of patients with liver and kidney diseases, reduce the need for more expensive downstream MR and CT imaging, and reduce overall imaging costs, according to a new study described today at the 31st annual Advances in Ultrasound conference in Chicago.
According to Dr. Edward Grant, a professor of medicine at the University of Southern California Keck School of Medicine, patients with liver and kidney masses identified on routine ultrasound scans were examined with CEUS at Los Angeles County General Hospital.  He and his colleagues determined that the hospital could anticipate a reduction of 339 CT and 53 MRIs annually by using contrast ultrasound tests first - a potential $132,000 cost reduction each year.
CEUS "is comparable to CT and MRI exams in its capacity to characterize liver and kidney lesions, such as hepatocellular carcinoma and hemangiomas," Dr. Grant said. "But what is remarkable is that CEUS results were usually added to the patient chart the same day, with over 72% done within 24 hours."
By comparison, the mean time to diagnosis and study completion was up to 52 days for CT exams and up to 123 days for an MRI, Dr. Grant added.
The study also found that CEUS reduced the need for CT and MRI follow up exams in the liver and kidney.  Dr. Grant noted that "66.7 percent of the CEUS exams were deemed of sufficient quality to not require further evaluation with CT or MRI."
"Ultrasound contrast agents are safe, low cost, and completely radiation-free imaging tools that can improve the clarity and reliability of front-line ultrasound scans of the heart and enhance the ability of routine CEUS scans to characterize tumors in the liver and kidneys.  They avoid unnecessary downstream testing, save lives and lower overall health care costs," according to Dr. Steven Feinstein, Co-President of the International Contrast Ultrasound Society (ICUS), who is an expert in cardiac CEUS and professor of medicine at Rush University Medical Center in Chicago.
He noted that previous studies in cardiac patients showed that CEUS could also cut costs and help avoid downstream testing in those populations.
"This is an outstanding example of patient-centered care, since CEUS provided same day diagnoses and avoided lengthy diagnostic delays associated with CT or MRI,"  according to Dr. Stephanie Wilson, Co-President of ICUS.  Dr. Wilson is an expert in abdominal CEUS and a professor of medicine at the University of Calgary in Canada.
"Coupled with the significant cost savings, CEUS offers an enormous improvement in patient management and care." she added.
Three ultrasound contrast agents, Definity (Lantheus Medical Imaging), Optison (GE Healthcare), and Lumason (Bracco Diagnostics) are available in the United States.  Definity and Optison  are approved by the Food and Drug Administration for cardiac imaging only, while Lumason is approved for both cardiac and liver imaging.
*View the original presentation delivered by Dr Ed Grant at the 31st Annual Advances in Contrast Ultrasound Bubble Conference by going to:

ICUS Weekly News Monitor 8-18-2016

1.  Dove Medical Press,  Aug 12,2016,  Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles      Authors:  Xiaozhou Fan, et al
2.  Science Daily,  Aug 9, 2016,  Researchers immobilize underwater bubbles
Source: American Institute of Physics, Authors: Zoubida Hammadi, et al
Dove Medical Press
Volume 2016:11 Pages 3939—3950
Aug 12,2016
Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles
Authors:  Xiaozhou Fan,1 Yanli Guo,1 Luofu Wang,2 Xingyu Xiong,1 Lianhua Zhu,1 Kejing Fang1
1Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Urology, Daping Hospital, Institute of Surgery Research, Third Military Medical University, Chongqing, People’s Republic of China
In this study, the lipid targeted nanobubble carrying the A10-3.2 aptamer against prostate specific membrane antigen was fabricated, and its effect in the ultrasound imaging of prostate cancer was investigated. Materials including 2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and polyethyleneglycol-2000 were for mechanical oscillation, and nanobubbles were obtained through the centrifugal flotation method. After mice were injected with nanobubbles, abdominal color Doppler blood flow imaging significantly improved. Through left ventricular perfusion with normal saline to empty the circulating nanobubbles, nanobubbles still existed in tumor tissue sections, which demonstrated that nanobubbles could enter tissue spaces via the permeability and retention effect. Fluorinated A10-3.2 aptamers obtained by chemical synthesis had good specificity for PSMA-positive cells, and were linked with carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid molecules from the outer shell of nanobubbles via amide reaction to construct targeted nanobubbles. Gel electrophoresis and immunofluorescence confirmed that targeted nanobubbles were fabricated successfully. Next, targeted nanobubbles could bind with PSMA-positive cells (C4-2 cells), while not with PSMA-negative cells (PC-3 cells), using in vitro binding experiments and flow cytometry at the cellular level. Finally, C4-2 and PC-3 xenografts in mice were used to observe changes in parameters of targeted and non-targeted nanobubbles in the contrast-enhanced ultrasound mode, and the distribution of Cy5.5-labeled targeted nanobubbles in fluorescent imaging of live small animals. Comparison of ultrasound indicators between targeted and non-targeted nanobubbles in C4-2 xenografts showed that they had similar peak times (P>0.05), while the peak intensity, half time of peak intensity, and area under the curve of ½ peak intensity were significantly different (P<0.05). In PC-3 xenografts, there were no differences in these four indicators. Fluorescent imaging indicated that targeted nanobubbles had an aggregation ability in C4-2 xenograft tumors. In conclusion, targeted nanobubbles carrying the anti-PSMA A10-3.2 aptamer have a targeted imaging effect in prostate cancer.
Science Daily
Aug 9, 2016
Researchers immobilize underwater bubbles
New technique to 'freeze' newly created microbubbles in their tracks could lead to new applications in medicine and the nuclear industry
Source: American Institute of Physics
Authors: Zoubida Hammadi, Laurent Lapena, Roger Morin, Juan Olives.
Immobilization of a bubble in water by nanoelectrolysis;  Applied Physics Letters, 2016; 109 (6): 064101 DOI: 10.1063/1.4960098
Controlling bubbles is a difficult process and one that many of us experienced in a simplistic form as young children wielding a bubble wand, trying to create bigger bubbles without popping them. A research team in CINaM-CNRS Aix-Marseille Université in France has turned child's play into serious business.
They demonstrated they could immobilize a microbubble created from water electrolysis as if the Archimedes' buoyant force that would normally push it to the surface didn't exist. This new and surprising phenomenon described this week in Applied Physics Letters, from AIP Publishing, could lead to applications in medicine, the nuclear industry or micromanipulation technology.
While bubbles are observed frequently in nature, it is not easy to control their diameter, position or time of formation. Previous work by the French research team explored how to control the hydrogen and oxygen gas bubbles formed by the breakdown of water using electricity. They showed that if one of the electrodes is tip-shaped -- with a curvature radius at its apex ranging from 1 nanometer to 1 micrometer -- and an alternating electric current with defnite values of amplitude and frequency was used, microbubbles could be produced at a single point at the apex of the nanoelectrode.
In the current work, the team has demonstrated a new and surprising phenomenon: the immobilization of a single microbubble in water. After a bubble is produced (at the apex of the nanoelectrode), it is immobilized by rapidly increasing the frequency of the electric current. It is a stable situation: No matter which direction the electrode moves, the bubble remains above and at the same distance from the electrode.
The scientists propose that the hydrogen or oxygen molecules enter the immobilized bubble through the lower surface and exit the bubble through the upper surface. The gas molecules are only produced at a single point at the apex of the nanoelectrode.
The team from CINaM-CNRS worked with researchers in acoustics who use ultrasounds for the detection and the characterization of microbubbles. They needed highly calibrated bubbles and the team proposed producing such bubbles using water electrolysis. The team incorporated a number of new ideas and methods in their approach. "While it is usual to consider that electrolysis is controlled by the electric potential, we show that the fundamental quantity is in fact the electric field which is why we use a tip-shaped electrode with a very small curvature radius at the apex," said Juan Olives, a member of the research team. The use of an alternating current of sufficient frequency then produces "nanoelectrolysis," which is the nanolocalization of the electrolysis reactions at a single point.
The greatest surprise in the findings was that, although nothing seems to move when you observe the experiment, in fact, all is moving in an apparent steady state, Olives said. Hydrogen and oxygen molecules are continually produced at the apex of the nanoelectrode, they move in the solution and in the bubble, they enter and leave the bubble, and there is a convection velocity in the solution and in the bubble. Everything is moving, except the surface of the bubble, Olives said.
Controlling microbubbles is critical to numerous applications in medicine including as ultrasound contrast agents, for breaking up blood clots, and for gas embolotherapy, which is the intentional blocking of an artery to prevent excessive blood loss. Controlling microbubbles is also important in the nuclear industry, where microbubbles in liquid sodium coolant can cause problems.

ICUS Weekly News Monitor 8-4-2016

1. Journal of Controlled Release,  Aug 28, 2016,  Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice       Authors:  Annemieke van Wamel, et al
2.  UMR Inserm U930,  Jun 30, 2016,  A New Dawn for Sonoporation with Creation of a Proof-of-Concept Consortium           Media release
Journal of Controlled Release
Volume 236, doi:10.1016/j.jconrel.2016.06.018
Aug 28, 2016,
Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice
Authors:  Annemieke van Wamela, Per Christian Sontumb, Andrew Healeyb, Svein Kvåleb, Nigel Bushc, Jeffrey Bamberc, Catharina de Lange Daviesa
a Dept. of Physics, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
b Phoenix Solutions AS, Oslo, Norway
c Joint Dept. of Physics, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK
Acoustic cluster therapy (ACT) is a novel approach for ultrasound mediated, targeted drug delivery. In the current study, we have investigated ACT in combination with paclitaxel and Abraxane® for treatment of a subcutaneous human prostate adenocarcinoma (PC3) in mice. In combination with paclitaxel (12 mg/kg given i.p.), ACT induced a strong increase in therapeutic efficacy; 120 days after study start, 42% of the animals were in stable, complete remission vs. 0% for the paclitaxel only group and the median survival was increased by 86%. In combination with Abraxane® (12 mg paclitaxel/kg given i.v.), ACT induced a strong increase in the therapeutic efficacy; 60 days after study start 100% of the animals were in stable, remission vs. 0% for the Abraxane® only group, 120 days after study start 67% of the animals were in stable, complete remission vs. 0% for the Abraxane® only group. For the ACT + Abraxane group 100% of the animals were alive after 120 days vs. 0% for the Abraxane® only group. Proof of concept for Acoustic Cluster Therapy has been demonstrated; ACT markedly increases the therapeutic efficacy of both paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice.
Graphical abstract
UMR Inserm U930
Jun 30, 2016
A New Dawn for Sonoporation with Creation of a Proof-of-Concept Consortium
Media release
TOURS, France - The Imaging and Ultrasound Team of the Imaging and Brain Inserm Unit U930 in Tours France, working in collaboration with colleagues at the Erasmus University Medical Center in Rotterdam, the Academic Medical Center in Amsterdam, the University Medical Center in Utrecht, (all 3 in the Netherlands), the University of Washington, Seattle USA and Advice-US Consulting, a Swiss Ultrasound Consultancy firm; have today launched a proof-of-concept research Consortium to evaluate the safety, tolerability and efficacy of sonoporation. This is a drug-delivery system based on the use of ultrasound and microbubbles in combination with oncolytic therapeutics to treat a range of tumour types in late-stage cancer patients. The Consortium tasked with the singular goal of translating sonoporation to the clinic is funded by a small pump-priming grant from LE STUDIUM® Loire Valley Institute of Advanced Studies, and brings together a multidisciplinary cohort of scientist, engineers and clinical practitioners (Prof Mike Averkiou, Dr Ayache Bouakaz, Dr Jean-Michel Escoffre Prof Nico de Jong, Dr Klazina Kooiman, Prof Heneke van Laarhoven, Prof Chrit Moonen, Dr Anthony Novell, Dr Charles A Sennoga and Prof Francois Tranquart). The Consortium’s scientific programme is led by Dr Ayache Bouakaz and coordinated by Dr Charles A Sennoga (both of Inserm U930). It is anticipated that the protocols developed, if clinically implemented will not only add a new cancer treatment to the clinical oncology toolbox but also go some way to filling existing gaps in our cancer management knowledge.
About Sonoporation:
It has long been recognized that ultrasound waves can facilitate the delivery of both large particles and therapeutic macromolecules into cells and other biological tissues by creating transient nonlethal perforations. Although this requires high acoustic power, well beyond that permitted for medical imaging, the power needed can be greatly reduced when microbubbles are used as an adjunct. This is because microbubbles lower the amount of energy necessary for cavitation, a process in which extreme oscillations induced by ultrasound pulses lead to microbubble collapse. As a result, cavitation of microbubbles in capillary beds increases capillary permeability, which improves local access of the released therapeutic agent. While the potential of sonoporation has already been harnessed as a drug-delivery tool in a wide range of pre-clinical studies, its application in humans is currently limited to a handful of publications. Guided by ultrasound images, researchers can now harness microbubble and ultrasound not only to home in on specific tumours and deliver drugs at precise targets but also monitor treatment response. For more information about sonoporation and the newly launched Sonoporation Consortium, please visit
About Imaging and Brain UMR Inserm U930
Founded in 2004, Inserm U930 seeks to empower this generation of creative scientists to transform medicine. The Inserm "Imaging and Brain" Research Unit U930 at Université François-Rabelais de Tours is interested in normal and pathological brain development, from the perinatal period to adulthood. The main focus of Inserm U930 is to develop, validate and clinically implement, new functional and structural brain imaging methods (MRI, PET, SPECT, EEG, ultrasound) in order to better characterize brain functioning and development; and to better understand brain pathological conditions. Inserm U930 seeks to develop effective new approaches for diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community. Inserm U930 includes faculty, professional staff and students from throughout the Faculty of Medicine, the biomedical research communities of the Université Francois-Rabelais and beyond, with additional collaborations spanning over several private and public institutions in many countries worldwide. For further information about the UMR Inserm U930, please visit

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