ICUS Weekly News Monitor 10-9-2015

1.  Gastroenterology and Endoscopy News,  Sep, 2015,  The Best of Digestive Disease Week 2015: Part 3      By Cynthia J. Gordon
 
2.  Business Wire ,  Sep, 23, 2015,  Research and Markets: Global Microbubbles/Ultrasound Contrast Agents Market to Reach $797.5 Million by 2021
 
3.  Ultrasound in Medicine and Biology,  Sep 1, 2015,  Quantitative Ultrasound Molecular Imaging     Authors: James Shue-Min Yeh, et al
 
4.  PLOS One,  Jul 10, 2015,  A Targeting Microbubble for Ultrasound Molecular Imaging     Authors: James Shue-Min Yeh, et al
 
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Gastroenterology and Endoscopy News
ISSUE: SEPTEMBER 2015 | VOLUME: 66:9
Sep, 2015
 
The Best of Digestive Disease Week 2015: Part 3
By Cynthia J. Gordon
 
In the final installment of this three-part series, two experts in endoscopy discuss some of their favorite presentations from this year’s Digestive Disease Week (DDW) meeting.
 
Contrast Enhanced Endoscopic Ultrasound of the Colon Is a Marker of Early Therapy Response Following Anti-TNF-Therapy in Patients With Acute Ulcerative Colitis (Ellrichmann M et al)
 
“When we treat patients with inflammatory bowel disease, our major goal is mucosal healing,” said Mark Ellrichmann, MD, MaHM, of University Hospital Schleswig-Holstein, in Kiel, Germany, at the DDW meeting. However, Dr. Ellrichmann added, “We don’t have an exact definition of mucosal healing due to all these different endoscopic criteria; we don’t have any guidelines for correct and optimal timing for the reevaluation; we don’t have any agreement about cutoff values for endoscopic scores; and … we don’t have any validated data to predict the therapy response at an early stage.”
 
Dr. Ellrichmann and his colleagues conducted a prospective, blinded, comparative study to evaluate the use of endoscopic ultrasound (EUS) of the colonic wall in patients with active ulcerative colitis (UC) undergoing treatment with the tumor necrosis factor (TNF)-α antibody adalimumab (Humira, AbbVie). Thirty-six patients with active mild, moderate or severe UC underwent EUS at baseline and at weeks 1, 4 and 12 after initiation of treatment with adalimumab. Data were compared with 20 healthy patients undergoing screening colonoscopy.
 
The researchers found that total colonic wall thickness measured by EUS was significantly higher in patients with active UC compared with healthy patients. Furthermore, patients with UC who responded to adalimumab had a significant decrease in total wall thickness after only one week of therapy, whereas nonresponders to adalimumab exhibited no changes in total wall thickness. Contrast-enhanced EUS showed that hypervascularity remained unchanged in nonresponders, whereas vascularity in responders normalized within a week of therapy. There was a positive correlation between histologic inflammation scores and total wall thickness throughout the treatment period (r=0.65; P<0.001). However, Mayo scores of disease activity did not correlate with total wall thickness after treatment.
 
“The combination of total wall thickness and contrast-enhanced ultrasound can be used as a marker of early therapy response to TNF-α antibody therapy, and possibly be used as a marker of nonresponse,” Dr. Ellrichmann concluded.
 
Dr. Bhutani: This study demonstrates that EUS can reveal what is happening in the colon wall beyond the superficial mucosal appearance.
 
Endoscopic ultrasound provides an objective measure of total wall thickness, and contrast-enhanced EUS provides dynamic information about hypervascularity within the colon wall. This study is very provocative and needs to be validated by other groups. I think this application of EUS is feasible in a clinical setting in the United States, but the procedure would most likely be performed at dedicated inflammatory bowel disease centers within referral hospitals, given the need for an expert in endosonography who has an interest in contrast-enhanced dynamic EUS. This procedure also might be useful in measuring response to therapy in UC patients in clinical trials.
 
 
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Business Wire
Sep, 23, 2015
 
Research and Markets: Global Microbubbles/Ultrasound Contrast Agents Market to Reach $797.5 Million by 2021
 
Research and Markets (http://www.researchandmarkets.com/research/h4r2k8/global) has announced the addition of the "Global Microbubbles/Ultrasound Contrast Agents Market Outlook: 2015-2021" report to their offering.
 
Microbubbles are composed of a gas core stabilized by a shell of proteins, lipids, or polymers and have the unique ability to respond to ultrasound, and thus are used as ultrasound contrast agents. The field of ultrasound contrast imaging has been literally bursting in the last decade. Incessant engineering advances in ultrasound technologies over the last decade have resulted in widespread usage of ultrasound for clinical applications. The potential benefits of ultrasound such as low-cost, convenience, and real-time capability of ultrasound images has led to wide acceptance of this technology. When compared with other imaging modalities, the ultrasound molecular imaging has many advantages such as good temporal resolution, quantitative data, real-time practice, noninvasiveness, relatively inexpensive cost, and no ionizing radiation.
 
Microbubbles/ ultrasound contrast agents for medical imaging have been swiftly translated from exploratory research to clinical application. It helps to sharpen the image, improve the reliability of the scan and reduce the need for unnecessary downstream testing. In addition, microbubbles can be employed for diagnostic imaging and as a therapeutic tool. These are safe, convenient, completely radiation-free, versatile, and routinely used by physicians throughout the world to obtain a reliable ultrasound diagnosis.
 
The global microbubbles/ ultrasound contrast agents market is expected to grow at a CAGR of 28.7% to reach $797.5 million by 2021 from 2015.
 
Key Topics Covered
1. Introduction to Global Microbubbles/Ultrasound Contrast Agents Market
2. Executive Summary
3. Market Insights
4. Microbubbles/Ultrasound Contrast Agents Market, Future Prospects, By Application
5. Microbubbles/Ultrasound Contrast Agents Market, Future Prospects, By Disease Area
6. Recent Researches on Microbubbles/Ultrasound Contrast Agents
7. Microbubbles/Ultrasound Contrast Agents Market, By Geography
8. Company Profiles
 
Companies Mentioned
• Bracco
• Daiichi Sankyo Company
• GE Healthcare
• Lantheus Medical Imaging
 
For more information visit http://www.researchandmarkets.com/research/h4r2k8/global
 
View source version on businesswire.com: http://www.businesswire.com/news/home/20150923005687/en/
 
Contact:
Research and Markets
Laura Wood, Senior Manager
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Sector: Medical Devices
 
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Ultrasound in Medicine and Biology
September 2015Volume 41, Issue 9, Pages 2478–2496
DOI: http://dx.doi.org/10.1016/j.ultrasmedbio.2015.04.011
Sep 1, 2015
 
Quantitative Ultrasound Molecular Imaging
Authors: James Shue-Min Yeh *yz;  Charles A. Sennoga zx; Ellen McConnell *;  Robert Eckersley z; Meng-Xing Tang {;  Sussan Nourshargh *k; John M. Seddon x; Dorian O. Haskard *; Petros Nihoyannopoulos*y
 
*National Heart and Lung Institute, Imperial College London, London, UK; yDepartment of Cardiology, Hammersmith Hospital, London, UK; zImaging Sciences Department, Medical Research Council, Imperial College London, London, UK; xDepartment of Chemistry, Imperial College London, London, UK; {Department of Bioengineering, Imperial College London,
London, UK; and kWilliam Harvey Research Institute, Queen Mary, University of London, London, UK
 
Abstract
Ultrasound molecular imaging using targeting microbubbles is predominantly a semi-quantitative tool, thus limiting its potential diagnostic power and clinical applications. In the work described here, we developed a novel method for acoustic quantification of molecular expression. E-Selectin expression in the mouse heart was induced by lipopolysaccharide. Real-time ultrasound imaging of E-selectin expression in the heart was performed using E-selectin-targeting microbubbles and a clinical ultrasound scanner in contrast pulse sequencing mode at 14 MHz, with a mechanical index of 0.22–0.26. The level of E-selectin expression was quantified using a novel time–signal intensity curve analytical method based on bubble elimination, which consisted of curve-fitting the bi-exponential equation Math Eq to the elimination phase of the myocardial time–signal intensity curve. Ar and Af represent the maximum signal intensities of the retained and freely circulating bubbles in the myocardium, respectively; λr and λf represent the elimination rate constants of the retained and freely circulating bubbles in the myocardium, respectively. Ar correlated strongly with the level of E-selectin expression (Math Eq), determined using reverse transcriptase real-time quantitative polymerase chain reaction, and the duration of post-lipopolysaccharide treatment—both linearly related to cell surface E-selectin protein (actual bubble target) concentration in the expression range imaged. Compared with a conventional acoustic quantification method (which used retained bubble signal intensity at 20 min post-bubble injection), this new approach exhibited greater dynamic range and sensitivity and was able to simultaneously quantify other useful characteristics (e.g., the microbubble half-life). In conclusion, quantitative determination of the level of molecular expression is feasible acoustically using a time–signal intensity curve analytical method based on bubble elimination.
 
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PLOS One
PLoS ONE 10(7): e0129681. doi:10.1371/
journal.pone.0129681
Jul 10, 2015
 
A Targeting Microbubble for Ultrasound Molecular Imaging
 
Authors:  James Shue-Min Yeh1,2,3, Charles A. Sennoga3,4, Ellen McConnell1, Robert Eckersley3, Meng-Xing Tang5, Sussan Nourshargh1,6, John M. Seddon4, Dorian O. Haskard1,
Petros Nihoyannopoulos1,2*
 
1 National Heart and Lung Institute, Imperial College London, London, United Kingdom, 2 Department of Cardiology, Hammersmith Hospital, London, United Kingdom, 3 Imaging Sciences Department, Medical Research Council, Imperial College London, London, United Kingdom, 4 Department of Chemistry, Imperial College London, London, United Kingdom, 5 Department of Bioengineering, Imperial College London, London, United Kingdom, 6 William Harvey Research Institute, Queen Mary, University of London, London, United Kingdom
* This email address is being protected from spambots. You need JavaScript enabled to view it.
 
Editor: Christoph E Hagemeyer, Baker IDI Heart and
Diabetes Institute, AUSTRALIA
 
Abstract
 
Rationale
Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound
molecular imaging. However, they often contain immunogenic (strept)avidin, which
impedes application in humans. Although targeting bubbles not employing the biotin-
(strept)avidin conjugation chemistry have been explored, only a few reached the stage of
ultrasound imaging in vivo, none were reported/evaluated to show all three of the following
properties desired for clinical applications: (i) low degree of non-specific bubble retention in
more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii)
effective for acoustic quantification of molecular targets to a high degree of quantification.
Furthermore, disclosures of the compositions and methodologies enabling reproduction of
the bubbles are often withheld.
 
Objective
To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation
chemistry for ultrasound molecular imaging.
 
Methods and Results
Microbubbles with a previously unreported generic (non-targeting components) composition
were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce
E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity
to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three
non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The
bubbles were effective for real-time ultrasound imaging of E-selectin expression in the
inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal
intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|0.8), demonstrating a high degree of non-invasive molecular
quantification.
 
Conclusions
Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)–(iii)
desired for clinical applications.

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