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

ICUS Weekly News Monitor 7-15-2016

1.  Ultraschall in Med 2016,  Jul 1, 2016,  Role of Contrast-Enhanced Ultrasound (CEUS) in Paediatric Practice: An EFSUMB Position Statement       Authors P. S. Sidhu, et al
2.  The Oregonian,  Jun 26, 2016,  OHSU-led study could help NASA's mission to Mars
By Lynne Terry
3.  National Space Biomedical Research Institute (NSBRI),  May 21, 2015,  NASA, NSBRI Select 24 Proposals to Support Crew Health of Astronauts on Deep Space Missions      Media Release
Ultraschall in Med 2016
Published online: 2016 Ultraschall in Med © Georg
Thieme Verlag KG Stuttgart ·New York · ISSN 0172-4614
Jul 1, 2016
Role of Contrast-Enhanced Ultrasound (CEUS) in Paediatric Practice: An EFSUMB Position Statement
Authors:   P. S. Sidhu1, V. Cantisani2, A. Deganello1, C. F. Dietrich3, C. Duran4, D. Franke5, Z. Harkanyi6,W. Kosiak7, V. Miele8, A. Ntoulia1, M. Piskunowicz9, M. E. Sellars1, O. H. Gilja10
Dr. Paul S. Sidhu
Radiology, King's College London, King's College Hospital
Denmark Hill, SE5 9RS London, UK
Tel.: ++ /44/2 03/2 99 41 64;  Fax: ++ 44/2 03/29 91 57
This email address is being protected from spambots. You need JavaScript enabled to view it.
The use of contrast-enhanced ultrasound (CEUS) in adults is well established in many different areas, with a number of current applications deemed “off-label”, but the use supported by clinical experience and evidence. Paediatric CEUS is also an “off-label” application until recently with approval specifically for assessment of focal liver lesions. Nevertheless there is mounting evidence of the usefulness of CEUS in children in many areas, primarily as an imaging technique that reduces exposure to radiation, iodinated contrast medium and the “patient-friendly” circumstances of ultrasonography. This position statement of the European Federation of Societies in Ultrasound and Medicine (EFSUMB) assesses the current status of CEUS applications in children and makes suggestions for further development of this technique.
The Oregonian
Jun 26, 2016
OHSU-led study could help NASA's mission to Mars
By Lynne Terry
Dr. Jonathan Lindner is head of imaging at the Knight Cardiovascular Institute at Oregon Health & Science University. For two decades, he's been looking for ways to identify the susceptibility for cardiovascular disease, in hopes of treating it at its inception.
Oregon cardiologists have hooked up with NASA to find better ways to screen astronauts who will take the next giant leap into space.
The National Aeronautics and Space Administration plans to send astronauts to an asteroid by 2025 and to Mars in the 2030s. But those missions will carry physical risks. In deep space, astronauts face being blasted with cosmic and solar radiation, threatening their cardiovascular systems.
The Oregon team, led by a cardiologist at Oregon Health & Science University, can't control the cosmos. But armed with a grant of nearly $1 million from the National Space Biomedical Research Institute, which works with NASA, they hope to uncover new ways to diagnose cardiovascular problems at an early stage to help astronauts and the rest of us.
"I will guarantee one thing and that is that this process is going to teach us a tremendous amount about how to treat people on Earth," said Dr. Jonathan Lindner, an OHSU cardiologist and lead investigator on the study. "To me, that's the big impact of this project."
Lindner's driving goal – one he's been pursuing for two decades – is to be able to thwart cardiovascular disease by identifying the disease early, when it's the most treatable. Right now, physicians are forced to scramble after symptoms, trying to slow progression of the disease and stem complications.
"There's not a cardiologist out there who has ever cured coronary disease," Lindner said. "We bypass it. We smush it. We stent it. We palliate it with medications. But nobody has ever cured anything."
Cardiologists know from studying the effects of radiation on Earth – from atomic bombs, radiation therapy and nuclear accidents – that it hurts the heart in multiple ways. It damages the muscle so it doesn't beat as well. It hurts the connective tissue, which becomes stiff. And it harms the lining of the blood vessels, which plays a key role in the build-up of plaque.
Atherosclerosis – the hardening of the arteries – can cause heart attacks, strokes and vascular disease.
While man-made radiation poses a risk on Earth, blasts from the sun do not. The planet's magnetic force defects them. But once astronauts leave low Earth orbit – where the International Space Station lives – they're bombarded by solar and cosmic radiation.
NASA can't build spacecraft to protect astronauts from all that radiation, Lindner said. The shielding would make the vessels too unwieldy.
And the threat from radiation can last a lifetime.
"The risk is not just around the time of being radiated," Lindner said. "It's lifelong."
His lab – and researchers at Oregon State University – will use advanced techniques to try to identify markers of cardiovascular disease beyond what's available now to use in the space program.
NASA chooses the fittest candidates who are in outstanding health. But they're picked long before they fly. As the years pass, their health changes, just like the rest of us.
"The reality is that cardiovascular disease is still a significant risk for any human being who's in their 40s, 50s or 60s," said Graham Scott, vice president and chief scientist of the National Space Biomedical Research Institute, which is partnered with NASA. "We would like to be able to detect at the earliest time possible if the cardiovascular status an astronaut is changing."
The idea would be to intervene early, with a drug, exercise regime or something else, to counteract that change.
Any new diagnostics that pass the necessary validation hurdles could even be used while astronauts are in flight or during the selection process.
The study will last two years and include 60 people between 35 and 55 who've undergone an advanced CT scan of the coronary blood vessels. Some might have a little plaque build-up. Others will have clear vessels. But no one admitted to the study will have severe blockage because those people would be excluded from the astronaut program.
Participants will undergo further testing. Researchers will use advanced imaging techniques developed at OHSU to check the health of their blood vessel linings. The endothelium, as its called, determines the susceptibility to developing plaque. It plays a key role in controlling inflammation and in the formation of blood clots.
Endothelial dysfunction is a harbinger of cardiovascular disease.
The final round of testing will involve blood tests. Scientists at OHSU and Oregon State University will analyze each person's blood, looking at their metabolism, genetics and the way their bodies handle lipids. These tests will reveal the "fingerprints" of how each person responds to their environment and offer clues about their susceptibility to disease.
Scientists will compare the tests, looking for connections. Any findings could lead to a new cardiovascular diagnostic test.
New tools will help NASA as it prepares to send men and women to Mars.
"Who are the people who are the most susceptible to atherosclerotic disease? That may help us determine candidacy for the astronaut program to Mars and for other deep space missions," Lindner said.
It could also help cardiologists – and patients -- here on Earth.
Once scientists figure out how heart disease starts, whether it's in response to radiation, a poor diet or inactivity, they'll have a key to preventing its progression and maybe even finding a cure.
National Space Biomedical Research Institute (NSBRI)
May 21, 2015
NASA, NSBRI Select 24 Proposals to Support Crew Health of Astronauts on Deep Space Missions
Media Release
NASA’s Human Research Program (HRP) and the National Space Biomedical Research Institute (NSBRI) will fund 24 proposals to help investigate questions about astronaut health and performance on future deep space exploration missions. The selected proposals will investigate the impact of the space environment on various aspects of astronaut health, including visual impairment, behavioral health, bone loss, cardiovascular alterations, human factors and performance, neurobehavioral and psychosocial factors, sensorimotor adaptation and the development and application of smart medical systems and technologies. All of the selected projects will contribute towards NASA’s future missions to Mars.
The selected studies represent how HRP and NSBRI work together to address the practical problems of spaceflight that impact astronaut health. HRP and NSBRI research provides knowledge and technologies that may improve human health and performance during space exploration. They also develop potential countermeasures for problems experienced during space travel. The organizations’ goals are to help astronauts complete their challenging missions successfully and preserve their long-term health. This applied research will be conducted in laboratory settings as well as ground-analog settings that mimic the spaceflight environment. Selected studies include one by Dr. Gary Strangman, Associate Professor at Massachusetts General Hospital in Boston, who will design, develop, and test a near infrared spectroscopy-electroencephalography system for sleep research in a realistic spaceflight analog environment. Dr. Valerie Meyers, a toxicologist at NASA’s Johnson Space Center in Houston, will examine the effects of carbon dioxide on cognitive performance in high-level decision-making in astronaut-like populations. Dr. Benjamin Levine, Professor in Internal Medicine at the University of Texas Southwestern Medical Center in Dallas, will assess the risk of atrial fibrillation in crewmembers participating in long-duration spaceflight missions.
The selected proposals are from 21 institutions in 11 states and will receive a total of about $12.9 million during a one- to three-year period. The 24 projects were selected from 178 proposals received in response to the research announcement entitled, “Research and Technology Development to Support Crew Health and Performance in Space Exploration Missions.” Science and technology experts from academia and government reviewed the proposals. NASA will manage 17 of the projects and NSBRI will manage seven. Six of the investigators are new to HRP and NSBRI.
HRP quantifies crew health and performance risks during spaceflight and develops strategies that mission planners and system developers can use to monitor and mitigate the risks. These studies often lead to advancements in understanding and treating illnesses in patients on Earth.
NSBRI is a NASA-funded consortium of institutions studying health risks related to long-duration spaceflight. The Institute’s science, technology and career development projects take place at approximately 60 institutions across the United States.
Listed below is the complete list of the selected proposals, principal investigators and organizations:
NASA Awards
•             Dr. Dorrit Billman, San Jose State University Research Foundation, “Training for Generalizable Skills & Knowledge: Integrating Principles and Procedures”
•             Dr. Kim Binsted, University of Hawaii, “Using Analog Missions to Develop Effective Team Composition Strategies for Long Duration Space Exploration”
•             Dr. Mary Bouxsein, Beth Israel Deaconess Medical Center, “Vertebral Strength and Fracture Risk Following Long Duration Spaceflight”
•             Ms. Toni Clark, NASA Johnson Space Center, “Computational Modeling to Limit the Impact Displays and Indicator Lights Have on Habitable Volume Operational Lighting Constraints”
•             Dr. Noshir Contractor, Northwestern University, “CREWS: Crew Recommender for Effective Work in Space”
•             Prof. Leslie DeChurch, Georgia Institute of Technology, “SCALE: Shared Cognitive Architectures for Long-term Exploration”
•             Dr. Douglas Ebert, Wyle Laboratories, “Evaluation of an Impedance Threshold Device as a VIIP Countermeasure”
•             Dr. Edward Foegeding, North Carolina State University, “High-Protein And Polyphenol Bar Formulations: Utilizing Whey Protein-Polyphenol Ingredients”
•             Dr. Adam Gonzalez, State University Of New York, Stony Brook, “Asynchronous Techniques for the Delivery of Empirically Supported Psychotherapies”
•             Dr. Kritina Holden, Lockheed Martin, “Electronic Procedures for Crewed Missions Beyond Low Earth Orbit (LEO)”
•             Dr. Benjamin Levine, University of Texas Southwestern Medical Center at Dallas, “Integrated Cardiovascular (ICV) 2.0: Assessing the Risk for Atrial Fibrillation in Astronauts During Long Duration Spaceflight”
•             Dr. Steven Lockley, Brigham and Women’s Hospital, Harvard Medical School, “Lighting Protocols for Exploration – HERA Campaign”
•             Dr. Valerie Meyers, NASA Johnson Space Center, “Effects of Acute Exposures to Carbon Dioxide upon Cognitive Functions”
•             Dr. Greg Perlman, State University of New York, Stony Brook, “Personality and Biological Predictors of Resiliency to Chronic Stress among High-Achieving Adults”
•             Dr. Raphael Rose, University of California, Los Angeles, “Asynchronous Behavioral Health Treatment Techniques”
•             Dr. Jeffrey Ryder, Universities Space Research Association, “Sweat Rates During Continuous and Interval Aerobic Exercise: Implications for NASA Multipurpose Crew Vehicle (MPCV) Missions”
•             Dr. Richard Simpson, University of Houston, “The Impact of Modeled Microgravity and Prior Radiation Exposure on Cytomegalovirus Reactivation and Host Immune Evasion”
NSBRI Awards
•             Dr. Henry Donahue, Pennsylvania State University, “Somatic Mutations in Muscle and Bone Exposed to Simulated Space Radiation and Microgravity”
•             Dr. Robert Hienz, Johns Hopkins University, “Countermeasures for Neurobehavioral Vulnerabilities to Space Radiation”
•             Dr. Jonathan Lindner, Oregon Health & Science University, “Biomarker Assessment for Identifying Heightened Risk for Cardiovascular Complications During Long-duration Space Missions”
•             Dr. Brandon Macias, University Of California, San Diego, “Validation of a Cephalad Fluid Shift Countermeasure”
•             Ms. Debra Schreckenghost, TRACLabs, “Quantifying and Developing Countermeasures for the Effect of Fatigue-Related Stressors on Automation Use and Trust during Robotic Supervisory Control”
•             Dr. Gary Strangman, Massachusetts General Hospital, Harvard Medical School, “Sleep Electroencephalography and Near-Infrared Spectroscopy Measurements for Spaceflight and Analogs”
•             Dr. Gary Strangman, Massachusetts General Hospital, Harvard Medical School, “Testing Mechanical Countermeasures for Cephalad Fluid Shifts”
NSBRI Contact:
Graham B.I. Scott, Ph.D.
Vice President, Chief Scientist, & Institute Associate Director
National Space Biomedical Research Institute, (NSBRI)
This email address is being protected from spambots. You need JavaScript enabled to view it.
Tel: (713) 798-7227

ICUS Weekly News Monitor 7-8-2016

  1. Journal of Ultrasound in Medicine,  Jul 1, 2016,  Role of Arrival Time Difference Between Lesions and Lung Tissue on Contrast-Enhanced Sonography in the Differential Diagnosis of Subpleural Pulmonary Lesions     Authors:  Jing Bai, MD,  et al
    2.  Journal of the American Society of Echocardiography,  Jul 1,  2016,  Safety and Efficacy of Cardiac Ultrasound Contrast in Children and Adolescents for Resting and Stress Echocardiography     Authors: Shelby Kutty, et al
    3.  ICI Meeting 2016,  Tel Aviv, Israel -- the International Conference for Innovations in Cardiovascular Systems (Heart, Brain and Peripheral Vessels) and High-Tech Life Science Industry
    Journal of Ultrasound in Medicine
    JUM July 1, 2016 vol. 35 no. 7 1523-1532
    Jul 1, 2016
    Role of Arrival Time Difference Between Lesions and Lung Tissue on Contrast-Enhanced Sonography in the Differential Diagnosis of Subpleural Pulmonary Lesions
    Authors:  Jing Bai, MD;  Wei Yang, MD; Song Wang, MD; Rui-Hong Guan, MD;  Hui Zhang, MD;  Jing-Jing Fu, MD; Wei Wu,, MD;  Kun Yan, MD
    Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, Beijing, China
    Address correspondence to Wei Yang, MD, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, 100142 Beijing, China.
    Objectives—The purpose of this study was to explore the diagnostic value of the arrival time difference between lesions and surrounding lung tissue on contrast-enhanced sonography of subpleural pulmonary lesions.
    Methods—A total of 110 patients with subpleural pulmonary lesions who underwent both conventional and contrast-enhanced sonography and had a definite diagnosis were enrolled. After contrast agent injection, the arrival times in the lesion, lung, and chest wall were recorded. The arrival time differences between various tissues were also calculated.
    Results—Statistical analysis showed a significant difference in the lesion arrival time, the arrival time difference between the lesion and lung, and the arrival time difference between the chest wall and lesion (all P < .001) for benign and malignant lesions. Receiver operating characteristic curve analysis revealed that the optimal diagnostic criterion was the arrival time difference between the lesion and lung, and that the best cutoff point was 2.5 seconds (later arrival signified malignancy). This new diagnostic criterion showed superior diagnostic accuracy (97.1%) compared to conventional diagnostic criteria.
    Conclusions—The individualized diagnostic method based on an arrival time comparison using contrast-enhanced sonography had high diagnostic accuracy (97.1%) with good feasibility and could provide useful diagnostic information for subpleural pulmonary lesions.
    Journal of the American Society of Echocardiography
    July 2016Volume 29, Issue 7, Pages 655–662
    Jul 1,  2016
    Safety and Efficacy of Cardiac Ultrasound Contrast in Children and Adolescents for Resting and Stress Echocardiography
    Authors: Shelby Kutty, MD, FASEcorrespondenceemail, Yunbin Xiao, MD, PhD, Joan Olson, RDCS, Feng Xie, MD, David A. Danford, MD, Christopher C. Erickson, MD, Thomas R. Porter, MD, FASE
    Small pilot studies of ultrasound contrast (UC) echocardiography in children have suggested that it is safe; therefore, larger scale evaluation of safety and efficacy in this population is of particular interest.
    This was a retrospective study (January 2005 to June 2014). Known intracardiac shunt was the only exclusion criterion. UC echocardiography was performed on commercially available ultrasound systems using Definity (3% infusion). When indicated, real-time myocardial contrast echocardiography was performed at rest and stress, with examination of myocardial contrast replenishment, plateau intensity, and wall motion. The primary outcome was short-term safety and efficacy (<24 hours).
    In all, 113 patients (55% male; mean age, 17.8 ± 3 years; age range, 5–21 years) underwent UC echocardiography for left ventricular opacification or stress wall motion and perfusion analysis. Diagnosis categories were congenital heart disease (30%), acquired heart disease (21%), and other (suspected cardiac complications of disease of other organ systems; 49%). Twelve patients (11%) with right ventricular systolic pressures > 40 mm Hg received UC without complications; four of these (33%) had the highest right ventricular–right atrial gradient recorded with ultrasound contrast–enhanced Doppler. Myocardial perfusion and/or UC echocardiography–detected wall motion abnormalities were seen in 13 patients (12%); four had confirmed correlations by angiography or magnetic resonance imaging. There were 13 instances of adverse events or reported symptoms during UC echocardiography. All symptoms and events were transient, all patients completed protocols, and there were no immediate sequelae.
    These data demonstrate the usefulness and safety of UC echocardiography in children and adolescents for a wide variety of indications. UC echocardiography provided myocardial perfusion and wall motion information important in clinical decision making.
    ICI Meeting 2016
    Organizing and Scientific Committee

ICI Meeting 2016, Tel Aviv, Israel – the International Conference for Innovations in Cardiovascular Systems (Heart, Brain and Peripheral Vessels) and High-Tech Life Science Industry will be taking place on December 4-6 2016 in Tel Aviv, Israel.  
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