Playing with bubbles for science: WashU researchers are developing a noninvasive way to diagnose brain cancer

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    ST. LOUIS, MO (St. Louis Post Dispatch) — Washington University scientists are developing a way to identify brain cancer without performing a risky surgery. The replacement: an ultrasound and tiny gas bubbles.

Researchers at the college are using bubbles to briefly open the blood-brain barrier — a protective layer of tightly packed cells lining blood vessels of the brain — to let brain-unique molecules pass through and become detectable in a common blood test.

Biomedical engineering professor Hong Chen and her team just finished testing the method on healthy pigs. Ultimately, they hope to use it on brain cancer patients so doctors can detect small bits of cancer in the blood and understand tumor composition without drilling a hole in the patient’s skull.

“I feel like there needs to be some sort of technology that drastically advances our understanding of cancer and brain cancer in particular,” said Christopher Pacia, a doctoral candidate and a main author of the study, published earlier this year. “I hope this technology is the one to really push the field forward.”

Brain cancer diagnosis usually starts with magnetic resonance imaging, or MRI, which allows doctors to locate a tumor in the patient’s brain. But to understand the tumor type and to make a decision about future treatment, a surgeon needs to perform a brain biopsy, drilling a small hole in the skull and carefully extracting a tumor sample with a long hollow needle.

Unlike other cancers, whose small shreds can be found floating in a patient’s blood, brain cancers are separated from the rest of the body by a barrier that doesn’t allow cancer bits to seep out into the blood circulation.

To briefly open up that barrier without causing bleeding and allow the tiniest scraps of cancer DNA to escape, Chen and her team have borrowed a common tool used in ultrasound imaging — tiny gas bubbles covered in a greasy shell.

Microbubbles, commonly used by radiology specialists, expand and contract when low-frequency ultrasound is applied.

When microbubbles are injected into a vessel, they start traveling along the blood flow to different parts of a patient’s body, including the brain. Once they reach their destination, scientists can apply low-frequency ultrasound to make the bubbles burst.

Microbubbles push on the blood vessels of the brain, disrupting the blood-brain barrier, explained Pacia. “When the bubbles start to expand and contract, they’re opening a door for the tumor biomarkers to be released into the blood circulation.”

The study showed the method is safe and doesn’t cause bleeding or brain damage in healthy adult pigs, whose brains and skulls are similar to humans. Researchers also proved they can detect brain-specific molecules in a pig’s bloodstream after the procedure.

“The method could have practical value in the future,” said Kullervo Hynynen, a professor of medical biophysics at the University of Toronto who pioneered the use of ultrasound as a noninvasive surgical tool. “But there are still many questions to explore.”

The next step for Chen and her lab is to test this method on pigs with brain cancer and detect genetic signatures of cancers that are commonly used in clinical testing. Even if they are successful, it will still be awhile before Chen can test the technique on human patients.

Right now, Pacia is working to ensure that their technique is comprehensive, reliable and safe.

Whether using a needle biopsy or an ultrasound technique, maximizing the number of detectable cancer markers while minimizing the possible damage is crucial, said Pacia.

Pacia hopes to someday see the technology in operating rooms worldwide, offering a straightforward solution to a complex problem.

“I was lucky enough to see this project progress from just the concept and brainstorming into an actual device and a published paper,” Pacia said.

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