ICUS Weekly News Monitor 2-20-2009

1.  EarthSystemScience,  Feb 20, 2009,    Manipulating magnet-coated bubbles
By R. Mark Wilson

2.  Medical News,  Feb 18, 2009,    Contrast Media: Safety Issues and ESUR Guidelines (Medical Radiology / Diagnostic Imaging)

Feb 20, 2009

Manipulating magnet-coated bubbles
By R. Mark Wilson

This news item was posted in physicstodayorg category and has 0 Comments so far.
 Gas bubbles in a liquid driven by acoustic waves can be used in a variety of contexts—for example, as contrast agents for ultrasound imaging, as a delivery system for therapeutic drugs, as catalysts for sonochemical reactions, and as scrubbers of surfaces. The bubbles’ compressibility, which allows their volume to oscillate in response to the varying sound pressure, accounts for the wide applicability. Unfortunately, spatial gradients in the pressure field can make it nearly impossible to control the bubbles’ oscillations and position simultaneously. Researchers at Nanyang Technological University in Singapore have now found a simple recipe to dress the bubbles in a 1-μm-thick coat of magnetite nanoparticles. The coat, which self assembles in solution, stabilizes the bubbles (typically 40–350 μm in diameter) without sacrificing their compressibility; they remain intact for more than 6 months in a light-tight drawer and their position in solution can be controlled with a simple household magnet. The figure here illustrates an example: The oscillation of a single 130-μm-wide bubble, subject to sound at a frequency close to its resonant frequency, sets up eddies (signified by arrows) in the surrounding fluid. After the acoustic field is turned off, a permanent magnet nudges the bubble to the right. (For an animated version, see The authors expect magnetic bubbles to serve as remotely controlled microfluidic mixers and pumps, and, more generally, as tools to test fundamental fluid mechanics concepts. (X. Zhao, P. A. Quinto-Su, C.-D. Ohl, Phys. Rev. Lett., in press.)

Medical News
Feb 18, 2009

Contrast Media: Safety Issues and ESUR Guidelines (Medical Radiology / Diagnostic Imaging)

* Publisher: Springer
* Number Of Pages: 254
* Publication Date: 2009-03
* ISBN-10 / ASIN: 3540727833
* ISBN-13 / EAN: 9783540727835

Product Description:
This second, revised edition of Contrast Media: Safety Issues and Guidelines, presented in a handy, easy to use format, provides an invaluable, unique and unparalleled source of information on the safety issues relating to contrast media.
It not only updates the successful first edition, but also contains a number of completely new chapters, for example on gadolinium-based contrast agents, meta-analyses in contrast media research and various regulatory issues. Comprehensive consideration is given to the many different safety issues relating to iodinated, MR, ultrasound and barium contrast media.

ICUS Weekly News Monitor 2-13-2009

1.  ZAMP Bionews,  Feb 12, 2009,    New Imaging Center To Help Make Better Diagnoses, Evaluate Drug Effectiveness     By Steve Benowitz

2.  European Journal of Echocardiography,  Jan 2009,    Detection of coronary artery disease with perfusion stress echocardiography using a novel ultrasound imaging agent: two Phase 3 international trials in comparison with radionuclide perfusion imaging      By Roxy Senior et al

ZAMP Bionews
Feb 12, 2009

New Imaging Center To Help Make Better Diagnoses, Evaluate Drug Effectiveness
By Steve Benowitz

Researchers at the Moores Cancer Center at the University of California, San Diego are taking advantage of a five-year, $7.5 million grant from the National Institutes of Health (NIH) and sophisticated imaging technologies at the newly established In Vivo Cellular and Molecular Imaging Center (ICMIC) - one of only eight in the country - to develop new ways to detect early cancers that require treatment and monitor the effectiveness of new molecular-based cancer therapies.

“We want to develop diagnostic tools that define the cancer at its earliest stage, not just whether it is there, but its characteristics,” said co-principal investigators Robert Mattrey, MD, professor of radiology at the UC San Diego School of Medicine.

The new center, which is led by Mattrey and co-principal investigator David Vera, PhD, professor of radiology, is one of only three such centers in the nation to receive funding recently from the NIH’s National Cancer Institute.

Researchers will focus initially on three main basic research projects - all of which are aimed at translating laboratory findings in animals to the clinic. Mattrey and recent Nobel Prize winner Roger Tsien, PhD, professor of pharmacology, chemistry and biochemistry at UC San Diego, are leading a project to improve the ability to characterize the aggressiveness of certain tumors. According to Mattrey, cancers that express an enzyme called a matrix metalloproteinase tend to be aggressive and are likely to spread. Such enzymes are instrumental in breaking down tissues, enabling cancers to escape and enter the bloodstream and/or lymphatic system and metastasize, or spread, to distant sites.

“Such cancers will stay local until they are able to break down the tissue matrix that allows loose cells to get out and seed distant tissues,” Mattrey said. “It’s thought that metastases develop this way.”

Mattrey and Tsien are developing imaging contrast agents to use with ultrasound that will help them detect such enzymes in prostate and breast cancers. Determining the likelihood that a cancer could be aggressive has implications for treatment decisions, especially for diseases where the treatment adds risk, Mattrey said. For example, a 60-year-old man who is diagnosed with aggressive prostate cancer might elect to undergo surgery, whereas a man with a slow-growing malignancy might decide to wait and let physicians monitor his tumor.

In another project, Vera and co-investigator Stephen Howell, MD, professor of medicine at the UC San Diego School of Medicine, will use nuclear imaging and ultrasound to virtually crawl inside of cancer cells and monitor the presence and activity of an experimental platinum-based chemotherapy drug - in essence to find out if the therapy is hitting its targets and working or not.

Because drugs are expensive, drug companies want to know if agents are hitting targets before they invest hundreds of millions of dollars in testing and development, rather than waiting the months that it can sometimes take for some drugs to have any kind of visible effect. Doctors and patients would like to know a therapy’s efficacy much sooner than that in order to pursue a different treatment option.

“It’s difficult to know if a drug is reaching its molecular target,” Mattrey explained. “It’s not just a matter of knowing that the drug reaches the tumor, but also if it was able to inhibit or stop the chemical reaction that it was designed to do.”

The team will develop an imaging ‘reporter’ molecule to attach to a chemotherapy agent, enabling physicians to tell where the drug went in the body and whether it reached the tumor with effective concentration.

In the third major project, Dwayne Stupack, Ph.D., assistant professor of pathology at the UC San Diego School of Medicine, is studying the use of tiny nanoparticles to image and detect changes in the blood vessels that serve tumors. Since tumors, in particular metastatic tumors, alter the behavior of their associated blood vessels, Stupack is hoping to develop a novel, sensitive imaging system that will detect these tumors at their earliest stages.

ICMIC is a shared university resource open to a wide range of disciplines, such as radiology, surgery and pharmacology, and also carries a teaching component. Researchers will educate fellows and faculty in the use of state-of-the-art imaging tools, particularly molecular imaging.

As part of its training mission, ICMIC will initiate a seminar series highlighting ongoing molecular imaging research, and will oversee the awarding of more than $200,000 annually to support UC San Diego researchers’ career development and pilot projects in in vivo molecular imaging research of cancer.

The Moores UCSD Cancer Center is one of the nation’s 41 National Cancer Institute-designated Comprehensive Cancer Centers, combining research, clinical care and community outreach to advance the prevention, treatment and cure of cancer.

European Journal of Echocardiography
Jan 2009

Detection of coronary artery disease with perfusion stress echocardiography using a novel ultrasound imaging agent: two Phase 3 international trials in comparison with radionuclide perfusion imaging

Roxy Senior1,*, Mark Monaghan2, Michael L. Main3, Jose L. Zamorano4, Klaus Tiemann5, Luciano Agati6, Neil J. Weissman7, Allan L. Klein8, Thomas H. Marwick9, Masood Ahmad10, Anthony N. DeMaria11, Miguel Zabalgoitia12, Harald Becher13, Sanjiv Kaul14, James E. Udelson15, Frans J. Wackers16, Richard C. Walovitch17, Michael H. Picard18 for the RAMP-1 and RAMP-2 Investigators

1 Department of Cardiovascular Medicine, Northwick Park Hospital, Watford Road, Harrow, Middlesex HAI 3UJ, UK
2 King's College Hospital, Denmark Hill, London SE5 9RS, UK
3 Cardiovascular Consultants, Mid America Heart Institute, 4330 Wornall Rd, Kansas City, MO 64111, USA
4 Servicio de Eco-Cardiologia, University Clinic San Carlos, Planta baja Sur. Puerta I, 28040 Madrid, Spain
5 Department of Cardiology, University of Bonn, Sigmund Freudstr. 25, 53105 Bonn, Germany
6 Department of Cardiology, La Sapienza University of Rome, Via del Policlinico 155, 00161 Rome, Italy
7 Cardiovascular Research Institute, 100 Irving St, Washington, DC 20010, USA
8 Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
9 University of Queensland/School of Medicine, Level 4, C Wing, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, 4102 QLD, Australia
10 Division of Cardiology, University of Texas, 301 University Blvd, Galveston, TX 77555-0553, USA
11 Cardiology Division, UCSD Med Center, 200 W. Arbor Drive #8411, San Diego, CA 92103, USA
12 University of Texus Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
13 John Radcliffe Hospital, Headley Way, Oxford 0X3 9DZ, UK
14 OHSU, UHN62, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
15 Division of Cardiology, Department of Medicine, Tufts-New England Medical Center, Boston, MA 02111, USA
16 Yale University School of Medicine, 333 Cedar Street Fitkin-3, New Haven, CT 06520, USA
17 Acusphere, Inc, 500 Arsenal Street, Watertown, MA 02472, USA
18 Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
* Corresponding author. Middlesex University, London; Imperial College, London; Northwick Park Hospital and Institute of Postgraduate Medical Education and Research. Tel: +44 208 869 2548; fax: +44 208 864 0075. E-mail address: This email address is being protected from spambots. You need JavaScript enabled to view it.


Aims: To determine if perfusion stress echocardiography (PSE) with ImagifyTM (perflubutane polymer microspheres) is comparable to stress perfusion imaging using 99mTc single photon emission computed tomography (SPECT) for coronary artery disease (CAD) detection. PSE is a novel technique for evaluating myocardial perfusion. RAMP (real-time assessment of myocardial perfusion)-1 and -2 were international, Phase 3 trials that evaluated the ability of PSE with Imagify, to detect CAD.

Methods and results: Chronic, stable, chest pain patients (n = 662) underwent Imagify PSE and gated SPECT imaging at rest and during dipyridamole stress. Independent blinded cardiologists [three PSE readers per trial, and four SPECT readers (one for RAMP-1, three for RAMP-2)] interpreted images. CAD was defined by quantitative coronary angiography or 90-day outcome with clinical review. Accuracy, sensitivity, and specificity were evaluated using non-inferiority analysis (one-sided alpha = 0.025) compared with SPECT. SPECT results for RAMP-1 and -2 were: accuracy (70%, 67%), sensitivity (78%, 61%), and specificity (64%, 76%). Accuracy of all six PSE readers was non-inferior to SPECT (66–71%, P  0.004). Four demonstrated non-inferior sensitivity (68–77%, P  0.002), three demonstrated non-inferior specificity (72–88%, P  0.013). Three PSE readers (RAMP-2) were superior for sensitivity. Two PSE readers (RAMP-1) were superior for specificity. Area under the multi-reader receiver operating characteristics curve (0.72) was equal for both modalities. Majority of adverse events followed dipyridamole dosing, and were mild, transient, and required no treatment.

Conclusions: Imagify PSE was well-tolerated. Its diagnostic performance in chest pain patients is comparable with SPECT perfusion imaging.

ICUS Weekly News Monitor 2-6-2009

1.,  Feb 5, 2009,    Ultrasound pulses keep drugs on target

2.  Atherosclerosis Journal,  Feb 2009,    Simplified contrast ultrasound accurately reveals muscle perfusion deficits and reflects collateralization in PAD     By Daniel Duerschmieda1 et al.

3.  Cordis News,  Feb 3, 2009,    EU-funded project to develop tiny particles that can deliver drugs directly to disease sites

4. News,  Feb 2, 2009,     New Journal for 2009 from Maney -  Bubble Science, Engineering and Technology.

5.  7th Space Interactive,  Jan 30, 2009,    Early onset lactating adenoma and the role of breast MRI: a case report     Author: Stefano Magno, et al.

Feb 5, 2009

Ultrasound pulses keep drugs on target

Royal Philips Electronics of the Netherlands is heading up a four-year, €15.9 million project to develop image-guided drug-delivery techniques. The SonoDrugs collaboration - which comprises fifteen European partners from industrial, medical and academic institutions - will investigate the use of ultrasound-activated particles to deliver drugs directly to disease sites.

While powerful drugs are available to treat certain types of cancers and cardiovascular disease, they are mostly administered as intravenous or oral doses, which limits control over their distribution in the body. With such "whole-body" dosing, the drugs can circulate in the patient's bloodstream and interact with many different tissues and organs, both diseased and healthy.

The SonoDrugs project will address this challenge by developing drug-delivery vehicles that can be tracked using real-time imaging and then triggered by focused ultrasound pulses to release the drug payload at the desired location. It's hoped that this controlled drug-delivery process will increase therapeutic efficiency and minimize side-effects, while also providing a means to tailor therapy to individual patients.

The drug-delivery vehicles will comprise nanoparticles (typically between 100 nm and 2000 nm in diameter) that can carry drugs to the site of disease via the bloodstream. Such small particles are easily transported by normal blood flow through the finest capillaries in the vascular system and can penetrate deep into diseased tissues.

The team will examine two particle types, the first of which has a shell made from a material that melts or becomes porous just above human body temperature (such as phospholipids, for example). The temperature rise required to melt the shell or increase its porosity - and thus release the contained drug - will be provided by the local heating effect of the focused ultrasound.

The second type of particle will be larger (up to 4 µm in diameter), with a shell that ruptures via pressure-induced stresses generated by the focused ultrasound pulses. Such gas-filled microbubbles are already in use as a ultrasound contrast agent and Philips Research has been investigating their application as a drug-delivery mechanism for several years.

The researchers also plan to employ two image-guidance modalities: MRI and ultrasound. MRI is ideal for use with thermally activated particles as it can be used to measure local tissue temperatures. It can also image soft tissues and locate particles labelled with MR contrast agents. Thus, MRI could be used to locate the target lesion and detect the arrival of the drug-loaded particles, and then provide accurate ultrasound focusing and controlled drug release using tissue-temperature measurements in a feedback loop.

The SonoDrugs project's work on MRI-guided drug delivery will focus primarily on potential treatments for cancer. Philips has already integrated the necessary ultrasound hardware and feedback mechanisms into its high-intensity focused ultrasound (HIFU) MRI research system using its phased-array ultrasound transducer technology.

For treatment of cardiovascular disease, the researchers will use ultrasound as the main imaging modality and as the means of releasing drugs from the particles. Here, the larger, pressure-sensitive particles will be used. This scheme is facilitated by the fact that gas-filled or partially gas-filled microbubbles show up well in ultrasound images.

"New therapeutic options such as externally triggered local drug release at the specific site of disease hold the promise to significantly improve patient care," said Henk van Houten, senior vice-president of Philips Research and head of Philips' healthcare research program.

"We realize that medical imaging technologies are only one of the enablers required to fulfil this promise," van Houten continued. "However, the wide-ranging expertise that has been brought together in the SonoDrugs project puts us in a strong position to ultimately deliver the benefits of image-guided drug delivery to patients and care providers."

• The SonoDrugs consortium comprises: Philips (the Netherlands, Germany, Finland); Nanobiotix (France); Lipoid (Germany); Erasmus Medical Center (the Netherlands); Universitäts Klinikum Münster (Germany); University of Cyprus (Cyprus); University of Gent (Belgium); University of Helsinki (Finland); University of London (UK); University of Tours (France); University Victor Segalen Bordeaux (France); University of Technology Eindhoven (the Netherlands); and University of Udine (Italy).

Atherosclerosis Journal
Feb 2009

Simplified contrast ultrasound accurately reveals muscle perfusion deficits and reflects collateralization in PAD

Daniel Duerschmieda1, Qian Zhoua1, Elisabeth Rinka, Dorothee Hardera, Gabriele Freunda, Manfred Olschewskib, Christoph Bodea, Christoph Hehrleina

Simplified contrast-enhanced ultrasound (CEUS) can be used to evaluate muscle perfusion in peripheral arterial disease (PAD). Here, we report its diagnostic accuracy for detecting symptomatic PAD. Additionally, we hypothesize that the extent of collateral formation is reflected by CEUS.

Ultrasound contrast agent was injected into an antecubital vein of 58 control subjects and 52 symptomatic PAD patients and its appearance in the calf muscle was evaluated. Interreader variability was tested using 118 raw data films. Arterial collateralization of PAD patients was assessed by angiographic imaging.

PAD patients showed a significantly longer median time to peak intensity (TTP, 36.9s) than control subjects (19.4s, p<0.001) with longer TTPs in advanced PAD stages. The area under the receiver operating characteristic curve was 0.942 and the mean TTP difference between two blinded readers was 0.28s. A TTP cut off at 30.5s was associated with 91% positive predictive value. PAD patients with good collateralization showed a significantly shorter TTP (34.1s) than patients with poor collateralization (44.0s, p=0.008) but not a higher ankle–brachial index (ABI).

CEUS accurately displays perfusion deficits of the calf muscle in symptomatic PAD patients. The degree of arterial collateralization is reflected by CEUS and not by ABI.

Cordis News
Feb 3, 2009

EU-funded project to develop tiny particles that can deliver drugs directly to disease sites

The EU-funded SonoDrugs project is developing tiny, image-guided capsules that will convey drug doses through the bloodstream to the site of disease, where they will be activated by ultrasound pulses. The new technology, which focuses on cardiovascular disease (CVD) and cancer, is expected to vastly improve therapeutic efficiency. The project has been financed with EUR 10.9 million under the Seventh Framework Programme (FP7) and brings together 15 academic and industrial partners from all over Europe.

Cancer and cardiovascular disease are two of the most common causes of death; the EU recorded 1.9 million deaths from CVD in 2003 and 1.2 million from cancer in 2004. Current treatments rely on 'whole-body' doses that are difficult to control and often come with undesirable side effects.

One of the goals of SonoDrugs is to ensure that drugs targeting cancer or cardiovascular disease provide the maximum benefit to the patient by being activated only where they encounter diseased tissue. This should certainly improve the efficiency of delivery, but it also avoids the problem of dosing all of the body's major organs.

The researchers are working to develop microscopic (100-2,000-nanometre-diameter) drug-loaded capsules that can be delivered through the bloodstream to diseased tissue, where they can release a dose of the drug on command. The very small size of the capsules allows them to be conveyed through the smallest blood vessels and well into the diseased tissues. The drug doses will be contained either within the particles themselves, or somehow attached to the shell.

Two particles will be designed: one with a shell that melts in response to the local heating effect of ultrasound, and a larger one that ruptures under pressure from ultrasound pulses. A different version of this second type of particle, often referred to as a 'microbubble', is already in use as a 'contrast agent' in ultrasound imaging.

Real-time magnetic resonance imaging (MRI) will be used to detect the arrival of the capsules at the desired destination. MRI is ideally suited to the project because it measures local tissue temperatures, locates lesions and tracks labelled particles easily. Once at their destination, the drug-loaded particles will be forced to release their dose, either by the heat or pressure from focused ultrasound pulses.

SonoDrug's MRI-guided drug delivery efforts focus on treatments for cancer; MRI techniques will be developed that will simultaneously detect the arrival of the labelled, drug-loaded particles at the disease site; measure the heating effect of ultrasound pulses; and monitor the temperature-triggered release of drugs from the particles.

The partners will explore potential treatments for CVD using ultrasound as both the primary imaging modality and the trigger for drug release from the pressure-sensitive microbubbles. One of the project partners, Philips Royal Electronics, will adapt its existing microbubble technology to deliver drugs; SonoDrugs will also make use of its integrated MRI/ultrasound research system.

'New therapeutic options such as externally triggered local drug release at the specific site of disease hold the promise to significantly improve patient care,' said Henk van Houten, senior vice president of Philips Research. 'We realise that medical imaging technologies are only one of the 'enablers' required to fulfil this promise. However, the wide-ranging expertise that has been brought together in the SonoDrugs project puts us in a strong position to ultimately deliver the benefits of image-guided drug delivery to patients and care providers.'

The researchers will also examine the potential of gas-filled microbubbles to increase the uptake of drug doses at the target sites in a process called 'sonoporation'. Sonoporation occurs when gas-filled microbubbles fracture in response to the stress induced by an ultrasound pulse; when this happens near a living cell, the cell's wall is impacted and becomes more porous. This makes the cell more willing to let in large drug molecules. This process is potentially quite useful for reducing the necessary doses in conventional 'whole-body' drug delivery. The way it works is not yet completely understood, and forms an exciting area of investigation for the project.

For more information, please visit:

Royal Philips Electronics:

_________________ News
Feb 2, 2009

New Journal for 2009 from Maney - Bubble Science, Engineering and Technology.

Professor Mohan Edirisinghe (University College London, UK), Dr Carlos Martinez (Purdue University, USA) and Maney Publishing are pleased to announce a new journal for 2009, Bubble Science, Engineering and Technology.
There is rapidly growing interest in the production and control of bubbles in numerous disciplines. Suspensions of stable gas microbubbles play a vital role in the food, cosmetics and pharmaceutical industries, as well as in biotechnology, environmental engineering, and minerals and materials processing. In molecular biology, microbubbles are central to the mesoscale self-assembly of smart materials, microfabrication and DNA-driven assembly. Microbubbles have also shown great promise in therapeutic applications such as targeted drug delivery, gene therapy, thrombolysis and ultrasound surgery, and are the most effective type of contrast agent available for ultrasound radiography.

Recent developments in processing, diagnostics and therapeutics have generated a greatly increased need for advanced preparation technologies that provide a high degree of control over microbubble characteristics. Achieving these objectives requires multidisciplinary collaboration and Bubble Science, Engineering and Technology will aim to provide an effective resource for researchers in bubbles research to facilitate these interactions.

The journal’s coverage will include drug and gene therapy, food science, medical physics, materials science and engineering, climate engineering, environmental engineering and biotechnology. Peer-reviewed contributions will address aspects such as:

Microbubble preparation and microencapsulation technologies;
Control and characterisation of bubble size and properties;
Functionalisation of bubbles, e.g. with nanoparticles, surfactants, pharmaceuticals and/or bioactive agents;
Applications of microbubbles in materials processing, medicine and imaging.

7th Space Interactive
Jan 30, 2009

Early onset lactating adenoma and the role of breast MRI: a case report
Author: Stefano Magno, Daniela Terribile, Gianluca Franceschini, Cristina Fabbri, Federica Chiesa, Alba Di Leone, Melania Costantini, Paolo Belli and Riccardo Masetti

Introduction: Lactating adenoma is a benign condition, representing the most prevalent breast lesion in pregnant women and during puerperium; in this paper, a case of a woman with lactating adenoma occurring during the first trimester of pregnancy is reported. There have been no reports in the literature, according to our search, focusing on magnetic resonance imaging findings in cases of lactating adenomas.

Also the early onset of the lesion during the first trimester of pregnancy is quite unusual and possibly unique.Case presentationWe report the case of a primiparous 30-year-old Caucasian woman, who noted an asymptomatic lump within her left breast during the 9th week of gestation, slightly increasing in size over the next few weeks. Ultrasound demonstrated a hypoecoic solid mass, hypervascularized and measuring 4cm.

On magnetic resonance imaging, performed in the first month after delivery, the lesion appeared as an ovoidal homogeneous mass, with regular margins and a significant contrast enhancement indicative of a giant adenoma.

Conclusion: Magnetic resonance imaging could play an important role in the differential diagnosis of pregnancy-related breast lumps, particularly during puerperium, thus avoiding unnecessary surgical biopsies.

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