Gas Embolotherapy ::
A Revolutionary Approach to Cancer Treatment

By Bill Clayton

THE SCENE HAS BEEN a staple on TV and in the movies: a scuba diver rises to the surface too rapidly and doesn't decompress. The sudden change in pressure damages his lungs, releasing a gas bubble that blocks the flow of oxygen-rich blood to his brain and vital organs. The diver - usually the bad guy - dies a tragic death.

Surgery and various traumas can also introduce small amounts of air into the blood stream, accidentally creating a "gas embolism" that blocks blood vessels and frequently has fatal results. It would seem that avoiding all gas emboli is the prudent course to follow. But gas emboli - and solid emboli - can be very useful.

In treating some forms of cancer, interventional radiologists and surgeons insert tiny catheters into arteries to inject solid emboli at strategic locations to block the supply of oxygen to tumors - in essence, starving the cancerous tissue to death. But the technique is awkward and imprecise.

Liquid droplets pass through capillaries to target
regions where ultrasound vaporizes them, creating
gas bubbles that lodge in selected capillaries and
occlude blood flow to starve and kill tumors.
ILLUSTRATION BY CAROLYN SMITH

Joe Bull, an assistant professor in the Department of Biomedical Engineering (BME), and Brian Fowlkes, an associate professor in BME and in the Department of Radiology in the University of Michigan Medical School, are researching a technique that'll change all of that.

"Our team is developing a novel gas embolotherapy method aimed at treating tumors by occluding blood flow to them and, secondarily, by the delivery of drugs," Bull said. "This technique is particularly well-suited for hepatocellular carcinoma."

Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a particularly insidious carcinoma that results in about 1,250,000 deaths worldwide each year. Surgical removal is difficult, and chemotherapy and radiation treatments aren't successful very often. Plus, the accompanying liver cirrhosis makes treatments even more difficult than usual.

"Rather than using solid emboli, our embolotherapy approach utilizes perfluorocarbon (PFC) gas bubbles that originate as liquid droplets - they're small enough to pass through capillaries," Bull said. "We inject them into the bloodstream, and when the droplets reach the target region, we use ultrasound to vaporize them. The resulting bubbles are 125 to 150 times the droplet volume, making them large enough to lodge in the circulation. This technique gives us the distinct advantages of being able to inject the dose of PFC droplets in a convenient location rather than only near the tumor. Then we can vaporize the droplets selectively to occlude the blood flow when they're close to the tumor. Our ongoing studies are aimed at uncovering the fundamental knowledge needed to develop effective embolization strategies for occluding flow to the entire tumor."

Although researchers have studied bubbles in many contexts, the investigation of bubble dynamics in gas embolotherapy is fairly new. Bull's group was the first to use fluidics experiments and mathematical modeling to explain the role of gravity and blood flow in the splitting of gas bubbles at vessel bifurcations. They're currently using this information to determine how close to the tumor PFC droplets should be in order to vaporize them and achieve uniform infarction.

The technique is truly a marvel of innovation that has the potential to save millions of lives, as well as eliminate the suffering and monumental costs associated with HCC.

-E

Program supported by NIH, NSF, The Whitaker Foundation.