Scientists at the Washington University School of Medicine in St. Louis have developed a new technique called “sonobiopsy,” a noninvasive brain biopsy that uses focused ultrasound and microbubbles to overcome blood-brain barrier obstacles that have typically hampered accurate diagnoses of brain diseases including cancer. The technique, reported in a study published in NPJ Precision Oncology, temporarily disrupts the protective barrier allowing RNA, DNA, and protein to spill into the blood stream where they can be collected and analyzed.
The technique, which was first developed and tested in animals has now been shown to be a feasible and safe for human use and could be used as method of noninvasively gathering samples for the detection of brain cancer and other brain diseases.
“Magnetic resonance imaging (MRI) revolutionized the field of brain disease diagnosis in the 1980s and ‘90s by allowing for structural and functional imaging of the brain,” explains co-senior author Eric C. Leuthardt, MD, a professor of biomedical engineering, mechanical engineering and neuroscience at Washington University. “Sonobiopsy is the third revolution, the molecular revolution. 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.”
The procedure, pioneered by Leuthardt and Hong Chen, PhD, an associate professor of biomedical engineering and neurosurgery, involves using focused ultrasound to accurately target a brain lesion—with accuracy down to the millimeter. This is followed by injecting microbubbles into the bloodstream. These microbubbles then travel to the targeted areas and pop, creating holes in the blood-brain barrier that close within a few hours and leave no lasting damage. These few hours is enough time for biomolecules from the targeted lesion to pass through the hole in the blood-brain barrier into the patients blood, where they can then be collected via a routine blood draw.
“We’ve essentially initiated a new field of study for brain conditions,” says Chen, the other co-senior author on the paper and co-inventor of the technology. “With this capability to noninvasively, nondestructively access every part of the brain, we can get genetic information on tumors before going in surgically, which would help a neurosurgeon determine how best to approach the surgery. If they see something suspicious on imaging, they could confirm whether a tumor is recurring or not. We can now start to interrogate diseases for which surgical biopsies aren’t done, such as neurodevelopmental, neurodegenerative, and psychiatric disorders.”
The new setup for this technique is a portable, handheld ultrasound probe integrated with a stereotactic pointer routinely used by neurosurgeons. This device, incorporated into the clinical workflow doesn’t require additional training, which makes sonobiopsy more accessible than the current, more expensive technology which integrates an ultrasound device with an MRI scanner.
For this study, the researchers used the device for sonobiopsies on five patients with brain tumors. The tumors were then surgically removed. Analysis of blood samples collected prior and after using the sonobiopsy technique showed that it had increased circulating tumor DNA 1.6-fold to 5.6-fold depending on which specific DNA was analyzed. The team also found there was no signs of any damage to brain tissue following the technique indicating the procedure is safe.
Leuthardt and Chen have previously published a paper on sonobiopsy in 2018 and note that it has already been adopted by some in the research community.
“Already there are multiple sites evaluating sonobiopsy in clinical trials around the world,” Chen said. “In one conference I attended recently, there was a whole session dedicated to sonobiopsy. This project exemplifies team science. Since introducing the concept of sonobiopsy in 2018, up to the publication of this clinical study, it has been a joint endeavor involving several investigators.”
