Clinical Trial Results: Noninvasive Brain Tumor Biopsy


Key Points

  • Data from a first-in-human safety and feasibility prospective clinical trial using “sonobiopsy,” or focused ultrasound–enhanced liquid biopsy, were recently published. 
  • The study, which enrolled five participants with brain tumors, noninvasively enriched blood circulating biomarkers that gave physicians detailed information about the brain tumors. 
Illustration of the neuronavigation-guided sonobiopsy setup.
Illustration of the neuronavigation-guided sonobiopsy setup.

Source: Yuan, J., Xu, L., Chien, CY. et al. First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound. npj Precis. Onc. 7, 92 (2023).

First-In-Human Prospective Trial of Sonobiopsy in High-Grade Glioma Patients Using Neuronavigation-Guided Focused Ultrasound 

The research (and device-designing) team led by Hong Chen, PhD, and Eric C. Leuthardt, MD, at Washington University in St. Louis (WUSTL) recently published data from their first-in-human prospective clinical trial using “sonobiopsy,” or focused ultrasound–enhanced liquid biopsy. The safety and feasibility pilot study enrolled five participants with brain tumors to test the technique, which has been patented by WUSTL. 

Importantly, brain tumor biomarkers – and biomarkers from other brain diseases – contain molecular and genetic information that can be used to diagnose and stage cancer, among other uses. Physicians can also use biomarkers to determine whether a treatment is working. 

With the goal of releasing disease-specific biomarkers (e.g., RNA, DNA, proteins) from the brain tumor into the circulating blood plasma, the WUSTL team developed a focused ultrasound device to target the brain tumor, then combined focused ultrasound with microbubbles to noninvasively open the blood-brain barrier (BBB) in that area to allow disease-specific biomarkers to flow from the tumor into the bloodstream. Without the sonobiopsy process, the biomarkers could not efficiently cross the BBB and enter the bloodstream to be measured. 

The WUSTL team designed the neuronavigation-guided focused ultrasound device for this project. Guided by a navigation system that is broadly used in the clinic for invasive brain biopsies, its ultrasound probe is portable and integrated with the clinical navigation system. This design enables easy integration of sonobiopsy into existing clinical workflows without requiring neurosurgeons to undertake additional training. First the probe is pointed at a target (the brain tumor). Then the team injects microbubbles into the bloodstream. When the microbubbles reach the brain, the focused ultrasound is turned on to oscillate the microbubbles and open the BBB. While the BBB is open, the molecules from the brain tumor move into the bloodstream. The physicians then use a regular blood draw to capture and measure the biomarker molecules. 

In the clinical trial, the blood samples collected before and after focused ultrasound sonication were compared with an analysis from the brain tumors after they were surgically removed. This comparison showed that the procedure was able to enrich patient tumor-specific circulating tumor DNA (ctDNA) in the blood. Histological analysis and transcriptome analysis of the sonicated brain tumor tissue found that focused ultrasound sonication was safe. 

In WUSTL’s press release, Dr. Leuthardt, who is the Shi Hui Huang Professor of Neurosurgery and a professor of biomedical engineering, mechanical engineering, and neuroscience at WUSTL, said, “…With this technique, we can obtain a blood sample that reflects the gene expression and the molecular features at the site of a lesion in the brain. It’s like doing a brain biopsy without the dangers of brain surgery.” 

Dr. Chen, an associate professor of biomedical engineering and of neurosurgery, says, “We have essentially initiated a new field of study for brain conditions. With this capability to noninvasively, nondestructively access every part of the brain, we can now obtain genetic information from tumors at every stage of patient care, ranging from tumor diagnosis to treatment monitoring and detection of recurrence. We can now start to interrogate diseases that traditionally do not undergo surgical biopsies, such as neurodevelopmental, neurodegenerative, and psychiatric disorders.” 

Going forward, the team is planning to conduct larger studies to determine the clinical utility of sonobiopsy. They also plan to fine-tune the way they localize and sonicate the region where the tumor is found. 

See npj Precision Oncology (Open Source) 

See WUSTL’s Press Release

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