Christopher Pacia –
Lifei Zhu
Jinyun Yuan
Yimei Yue
Hong Chen –

Washington University in St. Louis
4511 Forest Park Ave
St. Louis, MO 63108

Popular version of paper 3pBAb1
Presented Wednesday afternoon, December 9, 2020
179th ASA Meeting, Acoustics Virtually Everywhere

Brain cancer diagnosis starts with magnetic resonance imaging, or MRI, which allows clinicians to locate a tumor in the patient’s brain. However, MRI only provides anatomic information about the brain tumor. To understand the tumor type and to make a decision about future treatment, a neurosurgeon performs a tissue biopsy, drilling a small hole in the skull and carefully extracting a tumor sample with a long hollow needle. Liquid biopsy uses a blood sample to achieve similar information as the brain biopsy, without the need for surgery.

Unlike other cancers, whose small biomarkers, such as DNA, can be found circulating in a patient’s blood, brain cancers are separated from the rest of the body by the blood-brain barrier that does not allow tumor DNA to seep into the blood circulation. Two technologies are combined to briefly open the barrier: focused ultrasound and microbubbles. Focused ultrasound uses low-frequency ultrasonic energy to target tumors deep in the brain. Microbubbles are tiny gas bubbles commonly used in ultrasound imaging. When microbubbles are injected into a blood vessel, they travel along the blood flow to all parts of the patient’s body, including the brain. Once at the brain tumor, focused ultrasound causes the bubbles to expand and contract against the blood vessels in the brain, disrupting the blood-brain barrier and opening a door for the tumor DNA to be released into the blood circulation.

Video demonstrating the sonobiopsy technique to diagnose brain cancer.

The research presented here proves the success of sonobiopsy in increasing the levels of brain tumor biomarkers in the blood for the diagnosis of the most common and deadly brain tumor, glioblastoma, with different biomarker types and animal models. Sonobiopsy was optimized by increasing the amount of ultrasonic energy and the number of microbubbles injected to improve the number of biomarkers released in a mouse model. The utility of sonobiopsy was extended to different sized tumors and may be more effective for larger tumors, as demonstrated in a rat model. The potential for clinical translation was demonstrated by enhancing the release of brain-specific biomarkers in a pig model, with similar skull thickness as humans.

Sonobiopsy may be integrated into future clinical practice as a complement to MRI and tissue biopsies as an approach to noninvasively acquire molecular information of the tumor. The potential impact can be for the diagnosis of not only brain tumors but all other brain diseases. There are more studies to be done to better understand and optimize the technology before its practical value in humans, but this presentation is a step towards the future of brain cancer diagnosis.

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