Glioblastoma is a type of brain cancer that can be aggressive and, unfortunately, tricky to diagnose without a risky biopsy. But a new noninvasive method, tested in mice and pigs, could one day diagnose the disease with ultrasound pulses and a basic blood test.
The blood-brain barrier (BBB) is a crucial border lining blood vessel walls in the brain and central nervous system, to keep pathogens out of these sensitive places. Unfortunately, that can also make it hard to diagnose and treat cancers, neurodegenerative diseases and other illnesses affecting the brain.
Past work has shown that focused pulses of ultrasound can temporarily pry open this barrier, allowing drugs to get in to treat Alzheimer’s or cancer. But for the new study, researchers used ultrasonic pulses to open the blood-brain barrier in order to let something out instead.
The team, led by scientists at Washington University in St. Louis, started by injecting microbubbles into the bloodstream. Ultrasound pulses are then directed towards the brain, and when the passing microbubbles are struck by the waves they begin to pulsate. That holds the BBB open temporarily, allowing biomarkers of glioblastoma to escape into the blood. From there, doctors could diagnose the cancer through a simple blood test. They call this technique a sonobiopsy, and it should be far less invasive than a traditional biopsy.
The team tested the method in mice and pigs, and found that the biomarkers could be detected at much higher levels after sonobiopsy. They focused on two genes that are highly expressed in glioblastoma, EGFRvIII and TERT C228T. In mice, the amount of circulating tumor DNA (ctDNA) of EGFRvIII was 920 times greater after sonobiopsy, compared to mice that received a blood biopsy without ultrasound. Sensitivity towards the gene also rose from 7.14 percent to 64.71 percent, while levels of TERT C228T ctDNA increased by 10 times, with sensitivity improving from 14.29 to 45.83 percent.
In pigs, levels of EGFRvIII in the bloodstream rose by 270 times, and TERT C228T by nine times. Diagnostic sensitivity also rose from 28.57 to 100 percent for EGFRvIII, and from 42.86 to 71.43 percent for TERT C228T. In both mice and pigs, no major tissue damage was detected from the process.
“Our study showed that sonobiopsy enriched tumor-specific ctDNA in the plasma and improved the detection sensitivity for two glioblastoma phenotypes without posing significant safety risks,” says Hong Chen, lead author of the study. “The integration of sonobiopsy with advanced blood analysis assays has the promise to provide minimally invasive, spatiotemporal-controlled and sensitive diagnosis of brain cancer.”
The team says that sonobiopsy could eventually be used to diagnose brain tumors, monitor how their treatment is progressing, and keep an eye out for recurrence down the track. But there’s still plenty of work to do to investigate whether the results from these animal tests apply to humans.
The research was published in the journal Theranostics. The team describes the work in the video below.