microbubbles

A scanning electron micrograph of human red blood cells. Courtesy of Wellcome Images.

“Blood biopsies”

When a tumor grows beyond a certain size, it begins to shed cells, not unlike particles flaking off dry skin. Exactly when or why this happens in humans isn’t known, but these cells, called “circulating tumor cells” or CTCs play a major role in the spread of cancer to other parts of the body, the process more formally known as metastasis.

Scientists believe CTCs could be a new and invaluable source of information in the diagnosis and prognosis of cancer, but a big part of the current challenge is finding enough them: For every million or so circulating blood cells, there may be only a few CTCs. It’s the proverbial search for a needle in a haystack, only the needle is infinitesimally smaller and moving inside the human body. CTCs are also not generally inclined to announce their presence – at least not until they’ve lodged somewhere else (a distant organ, for example) to colonize and grow a new tumor.

The existing gold standard for isolating and identifying CTCs is an assay in which blood samples are exposed to magnetic beads coated with an antibody that binds to specific proteins on the surface of cancer cells. The capturing efficacy of this method ranges between 60 and 90 percent, but it also takes time and is prone to contamination from leukocytes – white blood cells that may also stick to the beads.

Recently, researchers at the University of California, San Diego School of Medicine and Moores Cancer Center described a new, alternative filtering technique that employs microbubbles. Writing in the March issue of PLOS One, principal investigator Dmitri Simberg, PhD, assistant project scientist, and colleagues said each microbubble is about half the diameter of a blood cell, filled with perfluorocarbon gas (for buoyancy and stability) and coated with an antibody. Exposed to a blood sample, the bubbles quickly attach themselves to any CTC encountered and puls them into a greater concentration (think soda bubbles rising to the top of a glass).

In tests using blood samples from mice and humans, Simberg said the microbubble assay worked better and faster than existing approaches, reducing the risk of contamination or sample degradation.

Though more research is required, he noted that the microbubble method may represent “the emerging field of blood biopsies, in which highly pure CTCs could be used as a source of tissue for personalized molecular diagnostics.”

It’s in the Blood: Microbubbles Help Biologist Jason Castle See Inside the Body

In emergency medicine, the “golden hour” is the time immediately following a trauma when intervention is most likely to save a life. Ultrasound researcher Jason Castle has experienced these critical moments first hand in his other role as a volunteer EMT in upstate New York. When he responds to emergencies, he often loses precious time trying to decode symptoms. “You try to understand the patient’s medical history, monitor the vitals and if you suspect a cardiovascular emergency, you take him to the hospital for tests,” say Castle, who works at GE Global Research in Niskayuna, NY..

Now, Castle is using his research skills to help speed treatment through “microbubbles,” tiny gas-filled spheres that can flow through the bloodstream, reflect sound waves and help define otherwise grainy ultrasound pictures. “Anywhere blood flows, these microbubbles can travel,” he says. “If you are in a car accident and have internal bleeding, we could tell right away, identify what organs have been injured and where the blood is pooling. These tests could be started as soon as the ambulance shows up, rather than waiting for arrival at the hospital.”

Top image: “When you inject these microbubbles, it’s like turning on the light inside the heart,” says GE biologist Jason Castle (above).

The new ultrasound technology could ride inside the ambulance and help medical staff diagnose patients on the spot, potentially saving lives. EMTs could deliver microbubbles in the vein through an ordinary IV injection. The bubbles dissolve minutes after the test and the gas leave the body in the breath. “When you inject these microbubbles, it’s like turning on the light inside the heart,” he says.

The biggest potential upside of microbubbles, however, is as a vehicle for delivering therapies. Castle and a team of GE scientists are experimenting with using microbubbles to ferry drugs, antibodies and even DNA payload to tumors, clogged arteries, and whole organs like the liver (see image below).

When they reach the target, doctors could change the acoustic setting of the ultrasound and burst the bubbles with sound waves. “You disrupt the bubble and deposit the drug where the body needs it most,” Castle says. “With great precision, you could deliver a full dose of chemotherapy to the tumor, right where it’s needed, reducing side effects. It could have a huge potential for the quality of life of cancer patients.”  In fact, a recently published study from Norway reported that microbubbles have been used in patients with pancreatic cancer.

Castle hopes that in the near future doctors could use microbubbles to image a patient’s heart and deliver anticlotting drugs at the same time. “Becoming an EMT as well as a biologist working to improve ultrasound gives you a chance to really see both fields,” he says. “As an EMT you see the current standards of care, how things are done, and how they could be done better.”

health.ucsd.edu
Air Apparent: Using Bubbles to Reveal Fertility Problems

New ultrasound procedure can identify blockages in fallopian tubes

Many women struggling to become pregnant may suffer from some degree of tubal blockage. Traditionally, an x-ray hysterosalpingogram (HSG) that uses dye is the most common procedure to determine whether a blockage exists, but it can cause extreme discomfort to the patient. UC San Diego Health System’s doctors are the first fertility specialists in the county to use a new ultrasound technique to assess fallopian tubes by employing a mixture of saline and air bubbles that is less painful, avoids x-ray exposure and is more convenient to patients during an already vulnerable time.

Using the FemVue Sono HSG, the physician delivers the mixture of saline and air bubbles into the uterus through a small catheter, which then flows into the fallopian tubes. Under ultrasound, the air bubbles are highly visible as they travel through the tubes, allowing the physician to determine if a blockage exists.

“The traditional x-ray approach involves higher pressure and usually causes significant cramping as the dye is administered. The anticipated pain prevents some women from even attempting the test. Others cannot do the test because they are allergic to the dye. Assessing the tubes for a blockage is a key component of the diagnostic workup in fertile couples, and not doing so because of pain or allergy is a real concern,” said Sanjay Agarwal, MD, director of Fertility Services in the Department of Reproductive Medicine at UC San Diego Health System. “The new approach is not only much more comfortable for patients, it also uses saline, so the issue of an allergy does not arise. We are also able to assess the cavity of the uterus at the same time - all without x-rays.”

Kristina, a mother who has been trying to conceive a second child for almost a year, agreed: “I was willing to do whatever it took to address the fertility issues we were facing, but after everything we had been through emotionally, it was a relief to undergo a procedure that wasn’t physically painful.”

The ultrasound is performed in the clinic, and at present, ideal candidates include those with a prior pregnancy and those at low risk for tubal disease. 

“Like the traditional x-ray HSG, the new test should be performed after the period has ended but before ovulation. The fact that the patient can schedule this ultrasound-based test in the clinic and not in radiology prevents a delay in care and allows the patient’s physician to be more involved in the process,” said Agarwal, also director of the UC San Diego Center for Endometriosis Research and Treatment (CERT).

Kristina said she was scheduled for the ultrasound just two days after her initial appointment and received the results from Agarwal in the clinic right after the procedure.

“I’m an impatient person, especially in this situation, so to immediately rule out a blockage in my fallopian tubes was a relief,” said Kristina, who will soon undergo fertility treatment.  

Reasons for blocked fallopian tubes often include an infection, endometriosis and prior surgeries. Agarwal says there is no cookie cutter treatment plan.

“Each case is unique, and if I find a blockage in the fallopian tubes, I work with my patient to formulate an appropriate treatment plan – one that is medically sound and is also acceptable to the patient,” said Agarwal, who performs one to three of the new ultrasound tests weekly.

Some of those treatment plans for women with tubal blockage may involve taking fertility medicines, having the diseased tube removed surgically or undergoing in-vitro fertilization.

“The ultrasound was a significant part of the puzzle, and now we are trying to fill in the missing pieces,” said Kristina. “I am hopeful and not giving up on my dream to have another baby.”

Who would’ve thought bubbles could be so revolutionary?

“The development of ultrasound contrast agents, containing encapsulated microbubbles, has increased the possibilities for diagnostic imaging. Ultrasound contrast agents are currently used to enhance left ventricular opacification, increase Doppler signal intensity, and in myocardial perfusion imaging. Diagnostic imaging with contrast agents is performed with low acoustic pressure using non-linear reflection of ultrasound waves by microbubbles. Ultrasound causes bubble destruction, which lowers the threshold for cavitation, resulting in microstreaming and increased permeability of cell membranes. Interestingly, this mechanism can be used for delivery of drugs or genes into tissue. Microbubbles have been shown to be capable of carrying drugs and genes, and destruction of the bubbles will result in local release of their contents. Recent studies demonstrated the potential of microbubbles and ultrasound in thrombolysis. In this article, we will review the recent advances of microbubbles as a vehicle for delivery of drugs and genes, and discuss possible therapeutic applications in thrombolysis…”

Read more

youtube

Bubbles in the blood: from the ‘bends’ to magic bullets
Dr. Eleanor Stride

“The presence of bubbles in the bloodstream is normally considered to be highly undesirable. Celebrated as the undetectable murder weapon in the plots of 1930s detective novels, they certainly represent an all too real hazard for deep sea divers and astronauts.

"There are, however, a rapidly growing number of biomedical applications in which bubbles can offer significant benefits. In this talk Eleanor Stride will describe how bubbles have transformed the state of the art in ultrasound imaging and are emerging as powerful therapeutic tools in treatments for major diseases including stroke and cancer.”

Global Contrast Media/Contrast Agents (Iodinated, Gadolinium, Barium, Microbubble) Market 2015 Forecasts and Trendsto 2020 for the $5.17 Billion Industry


DUBLIN, July 16, 2015 /PRNewswire/ – Research and Markets (http://www.researchandmarkets.com/research/ff25lf/contrast) has announced the addition of the “Contrast Media/Contrast Agents Market by Product (Iodinated, Gadolinium, Barium, Microbubble), by Procedure (X-Ray/CT, MRI, Ultrasound), by Application (Radiology, Interventional Radiology, Interventional Cardiology) - Global Forecasts to 2020” report to their offering.

The global contrast media market for the forecast period of 2015 to 2020. This market is expected to reach a value of $5.17 Billion by 2020, from $4.21 Billion in 2015, at a CAGR of 4.2% during the period under consideration. The market is expected to be dominated by North America in 2015, followed by Europe, Asia-Pacific, and RoW. The Asia-Pacific market is expected to grow at the highest CAGR during the given forecast period.

The global contrast agents market has been segmented on the basis of product, route of administration, indication, procedure, application, and region. In terms of product, the market is categorized into barium, iodinated, gadolinium, and microbubble contrast media. In 2015, the iodinated contrast media segment is estimated to account for the largest share of the contrast agents market, among the products. However, the microbubble contrast media market is expected to grow at the highest CAGR during the forecast period of 2015 to 2020.

On the basis of route of administration, the global market has been segmented into oral, injectable, rectal, and urethral routes. In 2015, the injectable segment is expected to account for the largest share of the market, among the different routes of administration.

The contrast media market, by indication, has been segmented into cardiovascular disorders, oncology, gastrointestinal disorders, musculoskeletal disorders, neurological disorders, and nephrological disorders. In 2015, the cardiovascular disorders segment is estimated to dominate the market, among indications.

Based on application, the market has been segmented into radiology, interventional radiology, and interventional cardiology. In 2015, the radiology segment is estimated to account for the largest share of the market, among the applications.

The key factors that are expected to drive the growth of this market include the increase in demand for diagnostics and image-guided procedures; increase in approvals for various contrast agents; and increase in aging population and the incidence of chronic diseases. In addition, the improving healthcare infrastructure in emerging markets and the increase in the number of public and private diagnostic centers are further propelling the growth of the global contrast media/contrast agents market. Moreover, the strong product pipelines of the major market players, along with the increasing research studies regarding applications of various contrast agents, are expected to provide opportunities for further market growth in the near future.

Some of the major players in the global market include Bayer Healthcare (Germany), GE Healthcare (U.K.), Guerbet Group (France), Bracco Imaging S.p.A. (Italy), Mallinckrodt PLC (Ireland), and Lantheus Medical Imaging (U.S.), among others.

Full List of Companies Mentioned

- Bayer Healthcare - Bracco Imaging S.P.A. (A Subsidiary Of Bracco S.P.A.) - CMC Contrast Ab - Daiichi Sankyo - GE Healthcare - Guerbet Group - Lantheus Medical Imaging - Mallinckrodt Plc - Nanopet Pharma Gmbh - Subhra Pharma Private Limited - Targeson, Inc. Pharma Co., Ltd.

For more information visit http://www.researchandmarkets.com/research/ff25lf/contrast

Media Contact:

Laura Wood, +353-1-481-1716, press@researchandmarkets.net



To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/global-contrast-mediacontrast-agents-iodinated-gadolinium-barium-microbubble-market-2015-forecasts-and-trendsto-2020-for-the-517-billion-industry-300116909.html

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arxiv.org
[1507.04829] Effects of ambient pressure on the subharmonic response from encapsulated microbubbles

[ Authors ]
Nima Mobadersany, Amit Katiyar, Kausik Sarkar
[ Abstract ]
Subharmonic response from contrast microbubbles as a function of ambient overpressure is numerically investigated for subharmonic aided noninvasive estimation of local organ level blood pressure. Three different interfacial rheological models for the encapsulation is used with material parameters appropriate for a common lipid coated contrast agent Sonazoid. The subharmonic response is seen to either decrease, increase or vary nonmonotonically with increasing ambient pressure. Compared to a free microbubbles important differences arise due to the encapsulation. Specifically due to the enhanced damping due to encapsulation, the range of excitation over which subharmonic is seen is broader than that in free microbubbles. This results in different trends of subharmonic response at the same excitation frequency for different excitation pressures. The observed behaviors are explained by investigating subharmonic generation threshold and resonance frequency.

Global Contrast Media/Contrast Agents (Iodinated, Gadolinium, Barium, Microbubble) Market Forecasts and Trends 2015-2020

Dublin, July 16, 2015 (GLOBE NEWSWIRE) – Research and Markets (http://www.researchandmarkets.com/research/cxnjm9/contrast) has announced the addition of the “Contrast Media/Contrast Agents Market by Product (Iodinated, Gadolinium, Barium, Microbubble), by Procedure (X-Ray/CT, MRI, Ultrasound), by Application (Radiology, Interventional Radiology, Interventional Cardiology) - Global Forecasts to 2020” report to their offering.



The global contrast media market for the forecast period of 2015 to 2020. This market is expected to reach a value of $5.17 Billion by 2020, from $4.21 Billion in 2015, at a CAGR of 4.2% during the period under consideration. The market is expected to be dominated by North America in 2015, followed by Europe, Asia-Pacific, and RoW. The Asia-Pacific market is expected to grow at the highest CAGR during the given forecast period.

The global contrast agents market has been segmented on the basis of product, route of administration, indication, procedure, application, and region. In terms of product, the market is categorized into barium, iodinated, gadolinium, and microbubble contrast media. In 2015, the iodinated contrast media segment is estimated to account for the largest share of the contrast agents market, among the products. However, the microbubble contrast media market is expected to grow at the highest CAGR during the forecast period of 2015 to 2020.

On the basis of route of administration, the global market has been segmented into oral, injectable, rectal, and urethral routes. In 2015, the injectable segment is expected to account for the largest share of the market, among the different routes of administration.

The contrast media market, by indication, has been segmented into cardiovascular disorders, oncology, gastrointestinal disorders, musculoskeletal disorders, neurological disorders, and nephrological disorders. In 2015, the cardiovascular disorders segment is estimated to dominate the market, among indications.

Based on application, the market has been segmented into radiology, interventional radiology, and interventional cardiology. In 2015, the radiology segment is estimated to account for the largest share of the market, among the applications.

The key factors that are expected to drive the growth of this market include the increase in demand for diagnostics and image-guided procedures; increase in approvals for various contrast agents; and increase in aging population and the incidence of chronic diseases. In addition, the improving healthcare infrastructure in emerging markets and the increase in the number of public and private diagnostic centers are further propelling the growth of the global contrast media/contrast agents market. Moreover, the strong product pipelines of the major market players, along with the increasing research studies regarding applications of various contrast agents, are expected to provide opportunities for further market growth in the near future.

Some of the major players in the global market include Bayer Healthcare (Germany), GE Healthcare (U.K.), Guerbet Group (France), Bracco Imaging S.p.A. (Italy), Mallinckrodt PLC (Ireland), and Lantheus Medical Imaging (U.S.), among others.



Full List of Companies Mentioned

- Bayer Healthcare
- Bracco Imaging S.P.A. (A Subsidiary Of Bracco S.P.A.)
- CMC Contrast Ab
- Daiichi Sankyo
- GE Healthcare
- Guerbet Group
- Lantheus Medical Imaging
- Mallinckrodt Plc
- Nanopet Pharma Gmbh
- Subhra Pharma Private Limited
- Targeson, Inc. Pharma Co., Ltd.



For more information visit http://www.researchandmarkets.com/research/cxnjm9/contrast



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arxiv.org
[1507.03090] A Non-stoichiometric Universality in Microbubble-Polyelectrolyte Complexation

[ Authors ]
Hiroshi Frusawa, Ryohei Yoshida
[ Abstract ]
We investigated the fundamental electrical properties of microbubbles (MBs) that are directly encapsulated by the addition of oppositely charged polyelectrolytes (PEs). Charge-reversal of the MB-PE complex particles has been observed by the microscopic electrophoresis method, revealing unusual overcharging behaviors in MB-PE complex solutions, as follows. The critical concentrations of cationic PEs added for overcharging were not only independent of their chain lengths and molecular species, but also much larger than stoichiometric neutralization points. Thus, we provide a theoretical sketch that considers the adsorption-desorption kinetics of small anions on the surface of genuine microbubbles, which can explain the inefficient charge-reversal.