Anatomically Precise Ultrasound-Based Technique to Enable Noninvasive Biopsies for Brain Tumors

The blood-brain barrier serves as a protective wall, keeping the brain safe from harmful elements like viruses and toxins in the blood. This makes it challenging for doctors to obtain molecular and genetic information, which could be critical for diagnosing and treating brain conditions like cancer. Typically, neurosurgeons have to perform risky surgical biopsies to gather this data, which is not an option for every type of brain disease or tumor. Now, researchers have developed a method called sonobiopsy, which uses ultrasound technology and microbubbles to temporarily disrupt this barrier, allowing vital molecules like RNA, DNA, and proteins to move into the bloodstream where they can be detected and studied.

Researchers at Washington University in St. Louis (WUSTL, St. Louis, MO, USA) who had developed and previously tested the technique in animals have now demonstrated the technique to be feasible and safe for use in humans, paving the way for noninvasive biopsies for suspected brain tumors and other brain diseases. The researchers had to rely on an expensive ultrasound setup that had to be integrated with an MRI scanner, limiting its usage to specific locations. To make the procedure more accessible, the team designed a portable handheld ultrasound probe which was attached to a stereotactic pointer that is commonly used by neurosurgeons for identifying brain lesions. This new device could be seamlessly incorporated into existing medical procedures without the need for extra training for the neurosurgeons involved.

The sonobiopsy technique involves focusing ultrasound on a particular brain lesion with millimeter-scale accuracy, followed by injecting microbubbles into the bloodstream. These microbubbles reach the targeted area and burst, creating small, temporary openings in the blood-brain barrier. These openings seal themselves within a few hours, causing no lasting harm. This brief window allows biomolecules from the lesion to escape into the blood, making it possible to collect them through a standard blood test. The researchers applied this method to five individuals with brain tumors, later surgically removing the tumors as per standard medical protocols. Blood analysis conducted before and after the sonobiopsy showed a significant increase in circulating tumor DNA levels—anywhere from 1.6 to 5.6 times, based on the specific type of DNA being analyzed. This DNA offers critical insights into the genetic makeup of the tumor, influencing how aggressively it should be treated. Additionally, there was no evidence of brain tissue damage, affirming the safety of the procedure.

“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,” said Eric C. Leuthardt, MD, co-inventor of the technology. “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.”

“We’ve essentially initiated a new field of study for brain conditions,” added Hong Chen, the 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.”

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