Gas Bubbles Used to Fight Tumors

Researchers are experimenting with gas bubbles used like corks to block oxygen flow to tumors or to deliver drugs.

The process of blocking blood flow to a tumor is called embolization, and using gas bubbles is a new technique in embolotherapy. What makes this method so promising is that the technique allows clinicians to control precisely where the bubbles are formed, so blockage of blood flow to surrounding tissue is minimal, according to Dr. Joseph Bull, assistant professor of biomedical engineering at the University of Michigan (U-M; Ann Arbor, USA).

The study of Dr. Bull and collaborator Dr. Brian Fowlkes, an associate professor in the department of radiology in the U-M Medical School, is currently focused on the vaporization and transport fundamentals that must first be determined to translate this developmental technique to the clinic.

In conventional embolotherapy techniques, the so-called cork that clinicians use to stop the blood flow--called an emboli--is solid. For instance, it could be a blood clot or a gel. A key problem with these approaches is restricting the emboli to the tumor to minimize destruction of surrounding tissue, without using very invasive procedures, according to Dr. Bull. The emboli must be delivered by a catheter placed into the body at the tumor site. Gas bubbles, however, allow very precise delivery because their formation can be controlled and directed from the outside, by focused high intensity ultrasound.

This planned technique is actually a two-step process, according to Dr. Bull. First, a flow of encapsulated superheated perfluorocarbon liquid droplets is delivered into the body by way of an intravenous injection. The droplets are small enough that they do not lodge in vessels. Clinicians image the droplets with conventional ultrasound, and once the droplets reach their destination, scientists blast them with high intensity ultrasound. The ultrasound acts like a pin popping a water balloon. After the shell pops, the perfluorocarbon expands into a gas bubble that is about 125 times larger in volume than the droplet.

"If a bubble remained spherical its diameter would be much larger than that of the vessel,” Dr. Bull said. "So it deforms into a long sausage-shaped bubble that lodges in the vessel like a cork. Two or three doses of bubbles will occlude most of the [blood] flow.” Without blood flow, the tumor dies. Because the bubble is so big, it is important to get the correct vessel in order not to damage it.

"How flexible the vessel is plays a very important role in where you do this,” Dr. Bull said. The embolotherapy study will be published in the August 2006 issue of the Journal of Biomechanical Engineering.

The technique could be very valuable in treating specific cancers, such as renal cancer and hepatocellular carcinoma, the most common form of liver cancer, which has a high mortality rate. However, cirrhosis of the liver makes it difficult to treat by the conventional method of excising the tumor and surrounding tissue, because so much of the liver is already damaged.



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