Focused Ultrasound Temporarily Opens Blood-Brain Barrier to Enable DNA Testing for Brain Tumors

The need for drilling into the skull and the potential complications of removing brain tissue, such as bleeding, brain swelling, or infection, make brain tumor biopsies particularly challenging. However, recent developments in noninvasive diagnostic methods have marked a significant advancement. Researchers are now exploring the use of focused ultrasound to collect DNA from brain tumors, representing a groundbreaking shift in brain tumor diagnostics.

Normally, a biopsy requires physically removing tissue from the body for examination. Tumors often release fragments of their DNA into the bloodstream, which can be detected and analyzed through a liquid biopsy. This method is already used for some cancers, offering a noninvasive way to repeatedly sample tumor DNA. However, detecting DNA from brain tumors is complex due to the blood-brain barrier, a protective vascular network that restricts substances from entering or leaving the brain. The new sonobiopsy technique uses focused ultrasound to temporarily disrupt the blood-brain barrier, allowing small molecules, like tumor DNA, to pass into the bloodstream. This DNA can then be collected through a simple blood draw for analysis. The process involves microbubbles, FDA-approved contrast agents used in ultrasound imaging. These microbubbles react to focused ultrasound waves by expanding and contracting, exerting mechanical force on blood vessel walls, thereby enhancing the permeability of the blood vessels.

In a pioneering clinical trial led by Washington University in St. Louis, researchers tested a compact focused ultrasound device on five patients with high-grade gliomas before their scheduled brain surgeries. The sonobiopsy was performed directly on the brain tumor, followed by blood sample collection and tumor removal. The blood and tumor tissue were then analyzed to identify tumor-specific DNA sequences. The study revealed that sonobiopsy significantly increased the detection of tumor-specific DNA in the bloodstream in three of the five patients. For one patient, the amount of detectable tumor DNA nearly doubled. While not all patients showed increased DNA levels in their blood, this variation was anticipated. Importantly, there was no detectable tissue damage on the brain's surface or in the tumor tissue exposed to focused ultrasound, indicating the procedure's safety.

“We are still in the developmental stage of this technology, and our trial was designed to use the tumor tissue taken from the brain as a benchmark to determine if the DNA found in the bloodstream was shed from the tumor following the sonobiopsy procedure,” explained Eric Leuthardt, M.D., Shi Hui Huang Professor of Neurosurgery at Washington University School of Medicine. “After we fully validate our method, the ultimate goal is to use a sonobiopsy to noninvasively analyze lesions in the brain to understand their molecular and genetic makeup to guide treatment decisions.”

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