ICUS Weekly News Monitor 1-6-2017

ICUS Weekly News Monitor
6 January, 2017 - 9am Eastern
1.  American Journal of Roentgenology,  Feb 1, 2017,  Retrospective Analysis of the Safety and Cost Implications of Pediatric Contrast-Enhanced Ultrasound at a Single Center    Authors:  Gibran T. Yusuf, et al
2.,  Jan 3, 2017,  Micro-Ultrasound in Cancer Research     By Susha Cheriyedath, MSc
3.  EFSUMB,  Educational Webinars Related to Ultrasound:  19 Jan  2017, 18:00 CET  --  CEUS LI RADS:  The New Classification of Focal Liver Lesions at Risk for HCC

American Journal of Roentgenology
Feb 1, 2017
Retrospective Analysis of the Safety and Cost Implications of Pediatric Contrast-Enhanced Ultrasound at a Single Center
Authors:  Gibran T. Yusuf1; Maria E. Sellars; Annamaria Deganello; David O. Cosgrove; Paul S. Sidhu
1All authors: Department of Radiology, King’s College
London, King’s College Hospital, Denmark Hill, London
SE5 9RS, UK. Address correspondence to G. T. Yusuf
( This email address is being protected from spambots. You need JavaScript enabled to view it. ).
OBJECTIVE. Because of concern over medical ionizing radiation exposure of children,
contrast-enhanced ultrasound (CEUS) has generated interest as an inexpensive, ionizing radiation–free alternative to CT and MRI. CEUS has received approval for pediatric hepatic use
but remains off-label for a range of other applications. The purposes of this study were to retrospectively analyze adverse incidents encountered in pediatric CEUS and to assess the financial benefits of reducing the number of CT and MRI examinations performed.
MATERIALS AND METHODS. All pediatric (patients 18 years and younger) CEUS
examinations performed between January 2008 and December 2015 were reviewed. All immediate
reactions deemed due to contrast examinations were documented in radiology reports.
Electronic patient records were examined for adverse reactions within 24 hours not due
to an underlying pathologic condition. With tariffs from the U.K. National Institute of Clinical
Excellence analysis, CEUS utilization cost ($94) was compared with the CT ($168) and
MRI ($274) costs of the conventional imaging pathway.
RESULTS. The records of 305 pediatric patients (187 boys, 118 girls; age range, 1
month–18 years) undergoing CEUS were reviewed. Most of the studies were for characterizing
liver lesions (147/305 [48.2%]) and trauma (113/305 [37.1%]); the others were for renal,
vascular, and intracavitary assessment (45/305 [14.8%]). No immediate adverse reactions occurred.
Delayed adverse reactions occurred in two patients (2/305 [0.7%]). These reactions
were transient hypertension and transient tachycardia. Neither was symptomatic, and both
were deemed not due to the underlying disorder. The potential cost savings of CEUS were $74
per examination over CT and $180 over MRI.
CONCLUSION. Pediatric CEUS is a safe and potentially cost-effective imaging modality.
Using it allows reduction in the ionizing radiation associated with CT and in the gadolinium
Jan 3, 2017
Micro-Ultrasound in Cancer Research
By Susha Cheriyedath, MSc
Cancer angiogenesis is a key focal point in biomedical research. However, lack of a high resolution and portable imaging technique that helps in non-invasive, real-time quantification of various parameters is a huge challenge facing cancer research studies in animals.
In cancer research, scientists need to visualize the tumor in real time, to study the effects of drugs on the tumor and aid in further drug discovery. In order to achieve this, they need imaging techniques that help them visualize tumor angiogenesis in a non-invasive manner in real time. Traditional methods including dissection and histology are not of much help in this regard. This is where micro-ultrasound tool is of great use to researchers.
Micro-ultrasound uses intravenous contrast agents and very high frequency probes to image tissues in fine detail. It is a promising technique for studying angiogenesis and monitoring therapy. Angiogenesis research is usually performed on mice, as they are easily available in many strains and are also easy to handle. Micro-ultrasound is particularly useful in this application due to the small size of the mice.
Why micro-ultrasound?
Several cancer research groups have used micro-ultrasound successfully in angiogenesis visualization. They reported the advantages of using micro-ultrasound as compared to conventional imaging tools such as CT, MRI, SPECT, and PET.
These systems have significant drawbacks including complicated operating requirements. None of them provide real-time visualization like micro-ultrasound, which can provide images at 300 frames per second, which helps analyze blood flow and perfusion. A study by Loveless et al showed that micro-ultrasound can be combined with MRI in order to validate results from both the tools.
Micro-ultrasound using contrast agents
Contrast agents used in micro-ultrasound improves imaging. These are materials which have optical or acoustic properties that are different from those of the target tissues, and are injected into the bloodstream.
Mechanism of drug action
New tools have emerged in the past decade for the targeted treatment of patients with metastatic lung, breast and renal cancer. However, understanding the mechanism of action of these drugs and identifying the category of patients that they benefit the most has been a challenge.
Also, there is a lack of biomarkers that can be used to track response to therapy as well as resistance to treatment. Micro-ultrasound is ideal for studying these aspects in preclinical models.
Tumor volume and changes
Micro-ultrasound provides a non-invasive way of repeatedly monitoring changes in a tumor over a long period of time. The same animal can be monitored, and acts as its own control. This boosts the accuracy of the study and reduces the number of animals required.
Using micro-ultrasound, tumors can be continuously monitored and measured right from initiation of therapy, through different stages of their growth, and during metastases to other organs, tissues and lymph nodes.
It has been shown by several studies that the use of micro-ultrasound enables accurate monitoring of tumor size. Images from 3D micro-ultrasound closely correlated with histology images and also precisely confirmed the tumor size and shape in vivo.
Other studies reported that 3D micro-ultrasound can not only be used for non-invasive monitoring of tumor volume and growth, but also for evaluating possible chemotherapeutic agents in murine cancer models.
Micro-ultrasound systems from Vevo and VisualSonics
A novel micro-ultrasound system developed by VisualSonics seems to be a promising solution to this problem. The revolutionary new technique allows collection of a large amount of data over the entire lifespan of the animals studied, thus reducing the number of animals required. The new system helps rapidly quantify tumor vascularity, 3D tumor volume, and tissue perfusion.
Vevo MicroMarker® contrast agents help in visualizing capillaries and monitoring the expression of VEGF and other such endothelial cell markers. Vevo® micro-ultrasound systems are widely used by cancer researchers. Olive et al. used the Vevo high-resolution micro-ultrasound system to create images of normal and diseased tissue in mice as part of a pancreatic cancer study. The researchers also successfully used the Vevo MicroMarker microbubbles to see tumor perfusion.
Reviewed by Liji Thomas, MD

EFSUMB Educational Webinars Related to Ultrasound
Register at:
This webinar will be offered free of charge.
Participation at the webinar is limited to a maximum of 100 participants. Online registration will be closed upon reaching the maximum numbers of participants.
Early registration is recommended!
Event speakers:
Moderator: Yuko KONO, Department of Medicine, University of San Diego, USA
18:00 Yuko Kono Welcome address. ACR plans illustration. Webinar information.
18:05 Fabio Piscaglia. Rationale and role of the CEUS LI RADS project in the international guidelines arena in 2017.
18:30 Stephanie Wilson Definition and illustrations of the CEUS LI RADS classes.

EFSUMB WEBINAR events are made possible through the generous support of Bracco  

ICUS Weekly News Monitor 12-22-2016

1.  Health Imaging,  Dec 19, 2016,  Contrast-enhanced sonography a ‘sound’ alternative in pediatric advanced imaging     By Dave Pearson
2.  Clinical Hemorheology and Microcirculation,  Dec 8, 2016
Percutaneous irreversible electroporation (IRE) of prostate cancer: Contrast-enhanced ultrasound (CEUS) findings during follow up    Authors: Beyer LP, et al

Health Imaging
Dec 19, 2016
Contrast-enhanced sonography a ‘sound’ alternative in pediatric advanced imaging
By Dave Pearson
Off-label use of contrast-enhanced ultrasound (CEUS) may be the best advanced-imaging choice—safe, accurate and cost-effective as compared to guideline-recommended CT and MRI—for examining children in many instances, according to a British study published online Dec. 13 in the American Journal of Roentgenology.
Gibran Yusuf, MBBS, and colleagues at King’s College Hospital in London concluded as much after reviewing the medical records of all pediatric patients who were imaged with CEUS at their institution between January 2008 and December 2015.
In total, they looked at 305 cases (187 boys, 118 girls; age range, 1 month to 18 years).
Most of the exams were for characterizing liver lesions (48.2 percent) and trauma (37.1 percent); the others were for renal, vascular and intracavitary assessment (14.8 percent).
None of the patients had immediate adverse reactions, the authors report.
Only two (0.7 percent) had delayed adverse reactions (0.7 percent), and both were asymptomatic and transient (hypertension and tachycardia).
The potential cost savings of CEUS were $74 per exam over CT and $180 over MRI, the authors calculate.
In their discussion, Yusuf et al. note that, in adults, CEUS has sensitivity and specificity comparable to that of CT and MRI.
They point out that CEUS can be safer than CT, as CEUS doesn’t involve ionizing radiation, and safer than MRI, as it almost never requires sedation or anesthesia, much less gadolinium-based contrast administration.
CEUS is generally the most cost-effective of the three advanced-imaging modalities—and the authors found the modality saved their institution almost $16,000 versus what the tab would have been had MRI and CT been used where indicated per institutional norms.
The authors caution that, while CEUS is safe, the use of any contrast calls for vigilance during and after administration.
They also acknowledge the imperfect diagnostic accuracy of CEUS.
“Correlating modalities were often performed before the CEUS examination; simultaneous cross-sectional diagnostic imaging was not performed for confirmatory purposes,” they write. “Patients undergoing sonographic examination were referred for further imaging if there was any doubt in the diagnosis, but there remains the possibility of misdiagnosis, as with all methods of imaging.”
Clinical Hemorheology and Microcirculation
vol. Preprint, no. Preprint, pp. 1-6, 2016
PMID: 27935553 DOI: 10.3233/CH-168125
Dec 8, 2016
Percutaneous irreversible electroporation (IRE) of prostate cancer: Contrast-enhanced ultrasound (CEUS) findings during follow up.
Authors: Beyer LP1, Pregler B1, Nießen C1, Michalik K1, Haimerl M1, Stroszczynski C1, Jung EM1, Wiggermann P1.
1Department of Radiology, University Medical Center Regensburg, Germany.
Irreversible electroporation (IRE) is a focal non-thermal ablation technique that can be used to treat prostate cancer (Pca). The objective was to document the evolution of the volume of the prostate gland and the ablation zone after IRE of Pca.
A retrospective analysis of the image findings of CEUS 1 day, 6 weeks, 3 months and 6 months after IRE of 25 patients was conducted. The prostate gland volumes and the size of the ablation zones were documented. Changes in volume and size over time were calculated.
There was a significant volume reduction of the prostate gland in the first 3 months after ablation. The mean percentage change after 6 weeks was 34.3% with another decrease of 35.0% after 3 months. Volume did not change between month 3 and 6. Size of ablation zone measured in short- and long-axis significantly diminished until 6 months after ablation.
CEUS showed a significant involution of the prostate gland during the first 3 months and a significant decrease of the ablation zone during the first 6 months after IRE of prostate cancer.

ICUS Weekly News Monitor 12-16-2016

1.  Theranostics,  Jan 1, 2017,  Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT)
Authors:  Andreas K.O. Åslund, et al
2.  Oncotarget,  Dec 14, 2016,  Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro     Authors:  Jing Ma, et al.
3.,  Dec 14, 2016,  IQ4I Research & Consultancy Published a New Report on “Ultrasound medical devices Global Market – Forecast To 2023”
Author: Monika Donimirska
4.,  Dec 12, 2016,  Nanomedical treatment concept combines NO gas therapy with starvation of tumor cells

Theranostics 2017; 7(1):23-30. doi:10.7150/thno.16577
Jan 1, 2017
Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT)
Authors:  Andreas K.O. Åslund1 Corresponding address, Sofie Snipstad1, Andrew Healey2, Svein Kvåle2, Sverre H. Torp3,4, Per C. Sontum2, Catharina de Lange Davies1, Annemieke van Wamel1
1. Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;
2. Phoenix Solutions AS, Oslo, Norway;
3. Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway;
4. Department of Laboratory Medicine, Children's and Women's Health, NTNU, Trondheim, Norway.
The blood-brain barrier (BBB) is a major obstacle in drug delivery for diseases of the brain, and today there is no standardized route to surpass it. One technique to locally and transiently disrupt the BBB, is focused ultrasound in combination with gas-filled microbubbles. However, the microbubbles used are typically developed for ultrasound imaging, not BBB disruption. Here we describe efficient opening of the BBB using the promising novel Acoustic Cluster Therapy (ACT), that recently has been used in combination with Abraxane® to successfully treat subcutaneous tumors of human prostate adenocarcinoma in mice. ACT is based on the conjugation of microbubbles to liquid oil microdroplets through electrostatic interactions. Upon activation in an ultrasound field, the microdroplet phase transfers to form a larger bubble that transiently lodges in the microvasculature. Further insonation induces volume oscillations of the activated bubble, which in turn induce biomechanical effects that increase the permeability of the BBB. ACT was able to safely and temporarily permeabilize the BBB, using an acoustic power 5-10 times lower than applied for conventional microbubbles, and successfully deliver small and large molecules into the brain.
DOI: 10.18632/oncotarget.13243
Dec 14, 2016
Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro
Authors:  Jing Ma1,2,3,*, Ming Shen4,*, Chang Song Xu5,*, Ying Sun4, You Rong Duan4, Lian Fang Du2
1Department of Ultrasound, Songjiang Hospital Affiliated to The First People’s Hospital of Shanghai Jiao tong University, Shanghai 201600, China
2Department of Ultrasound, Shanghai First People’s Hospital Affiliated to Shanghai Jiao tong University School of Medicine, Shanghai 200080, China
3Department of Ultrasound, Shanghai East Hospital Affiliated to Tong ji University, Shanghai 200120, China
4State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, P. R. China
5Huai’an First People’s Hospital, Nanjing Medical University, Jiangsu 223001, China
*These authors have contributed equally to this work
Correspondence to:
Lian Fang Du, email: This email address is being protected from spambots. You need JavaScript enabled to view it.
You Rong Duan, email: This email address is being protected from spambots. You need JavaScript enabled to view it.
A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic.
Dec 14, 2016
IQ4I Research & Consultancy Published a New Report on “Ultrasound medical devices Global Market – Forecast To 2023”
Author: Monika Donimirska
Ultrasound is a kind of imaging technique/procedure that makes use of high-frequency sound waves for scanning and creating an image of body part. Due to its less cost, best imaging quality, workflow efficiency, reliability, no requirement of same computing power, fast frame rates or specialized transducers now-a-days ultrasound scans are most popularly used diagnostic imaging technique.
Boston, MA, December 14, 2016 –(– Ultrasound is one of the renowned technologies in the medical field. This safe, non-invasive and non-use of ionizing radiation procedure involves sound waves of higher frequencies waves, (greater than 20,000 Hz) for producing various structural echo patterns of internal body parts. An ultrasound machine during diagnosis, works by bouncing off sound waves when in contact with solid parts of the body. In addition with the diagnosis, ultrasounds are being used to treat medical conditions too and thereby ultrasounds have role to play in therapeutic application. As estimated by IQ4I Research, Ultrasound medical devices global market is expected to grow at a double digit CAGR to reach $10,106 million by 2023.
Rising population of chronic and lifestyle disorder, availability of public-private investments, increasing demand for point of care testing and rising adoption of ultrasound technology in the various fields especially in cardiology, oncology and emergency medicine are the factors driving the market growth. However, some of the factors like lack of skilled professionals, high cost ultrasound devices, stringent regulations and unfavorable reimbursement cuts may hinder the growth of global ultrasound device market.
Advancements and newer technologies like contrast enhanced ultrasound and ultrasound elastography are revolutionizing ultrasound market. Contrast enhanced ultrasound technology which involves microbubble contrast agents and specialized techniques for imaging the blood flow and perfusion within the human body are becoming most popular medical imaging method. In September 7th, 2016 Toshiba America Medical Systems, Inc. announced its launch of Aplio 500 Platinum contrast enhanced ultrasound system after the recent approval from FDA for the use of microbubbles. Lumason and SonoVue from Bracco Diagnostics, Inc. (U.S.), Optison from GE Healthcare (U.S) are few FDA approved contrast enhanced ultrasound agents. Siemens Healthcare provides Cadence Contrast Pulse Sequencing (CPS) Technology on its ACUSON Sequoia Ultrasound platform providing detailed images of micro and macro vascularity enhancing lesion characterization. Philips HD11 XE has the versatility to expand into a complete digital imaging technology incorporating contrast imaging to enhance cardiovascular imaging capabilities. Similarly Ultrasound elastography is one of the emerging technologies where stress is applied on the organs to assess the mechanical properties (elasticity) and stiffness of fibrotic and cancerous lesions. Hitachi Medical Corporation has developed Real-Time Tissue Elastography (RTTE) application on its Hi Vision Avius ultrasound platform which differentiates the healthy and malignant tissues of breast, thyroid, prostrate, liver and pancreas. In addition the major players such as Toshiba Medical systems introduced elastography technique in its Aplio MX platform, Philips Healthcare on its iU22 platform and Siemens Healthcare in its ACUSON S2000 ultrasound platform.
The ultrasound medical devices global market is segmented based on their technology, display, portability, application, end users and geography. The market by technology is divided into diagnostic and therapeutic, based on display the market is segmented into black & white and color and based on portability market is divided into trolley/cart based and portable ultrasound medical devices. The ultrasound medical devices application is further sub-segmented into radiology/general imaging, women’s health, cardiology, point of care, urology, orthopedic, cancer, neurology and others. The radiology/general imaging occupied highest market in ultrasound medical devices application market.
Geographically, European regions held the largest market share where Germany accounted for the largest share, this growth is driven due to its high acceptance of advanced technologies and sophisticated universal treatment facilities. Among North American regions U.S. dominates, the market with the share of 77.9% and is expected to show a strong growth due to the high advanced healthcare facilities, increased growing awareness about the technological advancements, availability of Medicare and third party insurance facilities, easy availability of skilled personnel are driving the market growth. In Asia- Pacific region, Japan has held the largest market share due to its increase in healthcare spending and advancements in healthcare facilities, the easy access to advanced healthcare technology. In RoW regions, Brazil has the largest market share and is expected to grow at the strong rate due to increasing trends of medical tourism, large patient pool, Medicare facilities and increase in technological advancements.
Some of the prominent players in ultrasound medical device market include Analogic Corporation (U.S), Esaote (Italy), Fujifilm Holdings Corporation (Japan), GE Healthcare (U.S.), Hitachi Ltd (Japan), Koninklijke Philips N.V. (Netherlands), Mindray Medical International Limited (China), Samsung Electronics Co. Ltd (South Korea), Siemens AG (Germany) and Toshiba Medical Systems Corporation (Japan).
Dec 12, 2016
Nanomedical treatment concept combines NO gas therapy with starvation of tumor cells
Read more at:
Biocompatible nanocapsules, loaded with an amino acid and equipped with an enzyme now combine two anti-tumor strategies into a synergistic treatment concept. Researchers hope this increases effectiveness and decreases side effects. In the journal Angewandte Chemie, the scientists explain the concept: tumor cells are deprived of their nutrient glucose as this is converted to toxic nitrogen monoxide (NO) and hydrogen peroxide (H2O2).
NO is a toxic gas that causes smog. However, in low concentrations in the body it is an important messenger molecule that regulates such things as circulation and libido. It is also an important physiological defense weapon against fungi and bacteria. In higher concentrations, NO is capable of killing tumor cells and increasing the effectiveness of photodynamic and radiological treatments. For clinical use, NO needs to be released in the target area from a biocompatible precursor.
The natural amino acid L-arginine (L-Arg) may be useful in such a system, because the native enzyme inducible NO synthase (iNOS) makes NO from L-Arg. NO is also formed when L-Arg is oxidized by H2O2. This is interesting because the microenvironment around tumors is rich in H2O2. This approach to NO gas therapy is being pursued by researchers at Shenzhen University (China), the National Institutes of Health (Bethesda, USA), and the University of Maryland (College Park, USA). Their special twist is to combine this gas therapy with a method for starving cancer cells in a synergistic treatment.
Instead of starving a tumor by blocking the blood vessels that feed it, the researchers intend to remove the glucose that the tumor needs for nutrition by consuming it in a metabolic reaction: the enzyme glucose oxidase (GOx) converts the glucose into gluconic acid and H2O2. The increased H2O2 concentration is a useful side effect, because H2O2 is both cytotoxic and accelerates the release of NO from L-Arg. Another useful side effect is that H2O2 and NO react to form highly toxic peroxynitrites that damage the tumor cells.
The research team led by Peng Huang, Tianfu Wang, and Xiaoyuan Chen has now reached an important milestone in the development of this concept. They have developed biocompatible, biodegradable, porous nanocapsules made of organosilicates that transport GOx and L-Arg into tumor cells simultaneously. GOx is bound to the surface; L-Arg is stored inside the capsule. While the GOx is active immediately after injection of the nanocapsules into the tumor, L-Arg is released little by little, first through the capsule pores, then as the capsule disintegrates. Their large cavity also allows the capsules to serve as an ultrasound contrast material for better localization of the tumor.
Experiments with both cell cultures and mice have demonstrated the significant synergistic effect of this combination therapy, which successfully inhibits cell growth, initiates cell death, and shrinks the tumors in mice.

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