microbubbles

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.”

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.”

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…”

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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.”

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