Non-Invasive Brain Biopsy Improves Tumor Detection Sensitivity

Sonobiopsy is a technique that uses concentrated ultrasound to target tumors deep within the brain. Once the researchers have found the ultrasound-targeted region, they inject microbubbles into the blood, which pulsate and securely break the blood-brain barrier. Biomarkers from the tumor such as DNA RNA and proteins can pass across the blood-brain barrier and into the bloodstream thanks to the brief holes.

Non-Invasive Brain Biopsy Improves Tumor Detection Sensitivity

Tumors in the human body may lead to several unwanted medical conditions. However, every tumor does not prove to be a risk for life; in most cases, the scenario is the same that is life-threatening. A tumor in the brain can be highly dangerous, and it is also a tough task to remove the same. Experts have developed a new technology for the biopsy of such tumors in the brain.

Non-Invasive Brain Biopsy Improves Tumor Detection Sensitivity

Glioblastomas are malignant brain tumors that are often detected by a dangerous and invasive surgical biopsy. Hong Chen headed a team of researchers who created a non-invasive diagnostic procedure that could one day replace tissue biopsy with a simple blood test.

The approach was examined in both small and large animal models and found to have greatly increased detection and diagnostic sensitivity for brain cancers using a single blood sample, according to Chen, associate professor. The study’s findings were published online in Theranostics on November 10, 2021.

For several years Chen Leuthardt and the rest of the team have been working on their focused ultrasound-enabled liquid biopsy technology, first undertaking a feasibility study in mice, then a safety evaluation study and most recent research in pigs. While blood-based liquid biopsy has been utilized for customized therapy in human patients with various diseases, progress in applying the technology to human brain cancer has been slow.

Furthermore, after sonobiopsy discovery of another circulating tumor genetic marker TERT C228T ctDNA was 10-fold greater. Furthermore, the approach increased diagnostic sensitivity for EGFRvIII from 7.14 percent to 64.71 percent and for TERT C228T from 14.29 percent to 45.83 percent. After the sonobiopsy, the scientists discovered no increase in tissue damage in the tumor location of interest.

The team, which included Christopher Pacia, lead author and a biomedical engineering Ph.D. student in the Chen Ultrasound group, discovered that the sonobiopsy approach improved detection of highly expressed genes in the EGFRvIII mouse model of glioblastoma. The group that had sonobiopsy had 920 times more EGFRvIII DNA circulating in their bloodstream than the group that had a traditional blood-based liquid biopsy.

Sonobiopsy elevated the detection of EGFRvIIIctDNA by 270-fold in the pig model and increased TERT ctDNA levels by nine-fold. It increased diagnostic sensitivity for EGFRvIII from 28.57 percent to 100 percent

 and for TERT C228T from 42.86 percent to 71.43 percent. There was no evidence of severe tissue injury.

“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,” Chen said. “The integration of sonobiopsy with advanced blood analysis assays has the promise to provide a minimally invasive spatiotemporal-controlled and sensitive diagnosis of brain cancer.”

Eric Leuthardt, MD chief of the Division of Neurotechnology and the Center for Innovation in Neuroscience and Technology and professor of neurosurgery and neuroscience at the School of Medicine as well as biomedical engineering, mechanical engineering, and applied science at the McKelvey School of Engineering, led the effort.

“Besides neuroimaging and surgically-acquired tissue for pathology and molecular profiling sonobiopsy has the potential to become the third pillar for brain tumor management by substantially advancing brain cancer diagnosis treatment monitoring and recurrence detection,” Leuthardt said. “This enhanced capability could have an important impact throughout the continuum of patient care.”

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