Ultrasound News: Lowering the Barrier to Entry
By Josh Hildebrand
Radiology Today
Vol. 25 No. 2 P. 28
Physicians have numerous methods for diagnosing suspected brain tumors. Standard imaging procedures such as head CTs, brain MRIs, and brain PET scans may be used to determine if a patient has a tumor. When a mass in the brain has been detected, to determine whether it is malignant or benign, physicians will typically suggest a brain biopsy to gather a cell sample for analysis. Despite their ubiquity, brain biopsies are inherently risky. Complications such as brain bleeding and damage to brain tissue can occur.1 A 2012 analysis of brain biopsy safety found that procedure-related morbidity ranged from 0% to 12%.2 Furthermore, mortality rates are typically less than 2% and are commonly the result of severe biopsy-related hemorrhage.
A study published in 2021 analyzed 93 patients, showing that 86% received needle biopsy.3 Until recently, these needle biopsies were seen as the primary way to gather the genetic information necessary to make declarations regarding the nature of a tumorous brain mass.
However, in September 2023, a team of researchers from Washington University in St Louis published a study in NPJ Precision Oncology discussing a new way to obtain this information from the brain by accessing the blood-brain barrier. The blood-brain barrier’s primary function is the transportation of vital substances for brain function, as well as shielding the brain against viruses and various harmful substances, and separating blood from brain fluid.4 The researchers discovered that if they could temporarily disrupt the barrier, they would have access to genetic data essential for diagnosing and treating various brain diseases, without the need for traditional brain biopsy.
Sonobiopsy at a Glance
Researchers coined the term “sonobiopsy” to describe their new imaging technique. Focused ultrasound is used to target the tumor and microbubbles, commonly used as a contrast agent in ultrasound imaging, home in on the tumor, erupting in a burst of tiny bubbles that open holes where they meet the blood-brain barrier. RNA, DNA, and proteins from the brain then enter the bloodstream, where they can be safely and effectively extracted via blood draw, providing physicians with the genetic information necessary to identify and/ or treat the tumor.5 While the prospect of tiny holes in the blood-brain barrier might sound frightening, there is little cause for concern as the barrier mends itself within a few hours, leaving no lasting damage.
Hong Chen, an associate professor of biomedical engineering and neurosurgery at Washington University in St Louis and cosenior author of the study, says the blood-brain barrier has always been an area of interest for research due to its ability to hinder certain brain treatments.
“It’s widely recognized as a significant obstacle for effective drug delivery in the brain,” Chen says. “We hypothesized that opening the blood-brain barrier might enable a ‘two-way transfer’ which would allow drugs from the bloodstream to reach the brain and enable the release of disease-specific biomarkers.”
Part of Chen’s role at Washington University in St Louis, as a member of the division of neurotechnology in the department of neurosurgery, is advancing diagnostic solutions for the treatment of neurologic diseases. When the sonobiopsy research began, the team used a commercial focused ultrasound device that was integrated with an MRI scanner, which confined the team to spaces where that imaging technology was readily available. It was large, expensive, and ultimately deemed unfeasible. Chen and part of the research team subsequently developed and implemented a new portable, handheld device to break free of their confines. An ultrasound probe was attached to a stereotactic pointer, a targeting device, and used as a “neuronavigation system.”5 When a target is locked, microbubbles are released, and the bloodbrain barrier is disrupted.
“The reduced cost of our device, compared to MRI-guided alternatives, lowers the barrier to adopting this technology,” Chen says. “It enables the sonobiopsy procedure to seamlessly blend into existing clinical workflows without necessitating extra training for neurosurgeons.”
A Promising Future
The researchers at Washington University in St Louis are credited with having conducted the first human prospective trials using sonobiopsy on five patients with brain tumors.5 Since the publication of their research, interest in sonobiopsy has greatly increased. According to Chen, there are multiple health care practices evaluating the efficacy of sonobiopsy in clinical trials around the world.
“Although the data shows great promise in the feasibility and safety of sonobiopsy, this pilot study was limited in scope,” Chen says. “To confirm these initial findings and establish the clinical utility of sonobiopsy, further studies with larger sample sizes are necessary.”
Interest in the efficacy of sonobiopsy goes beyond that of replacing traditional brain biopsies. In January of 2023, Chen was part of another study published in Radiology using focused ultrasound to detect the biomarkers of neurodegeneration in mice. Much like the initial sonobiopsy study in human patients, results from the study showed the efficiency with which sonobiopsy disrupted the blood-brain barrier to release biomarkers of neurodegenerative diseases into the blood. Chen is hoping to continue expanding this research to determine additional uses for sonobiopsy.
“We are exploring its application in enhancing the detection of circulating biomarkers for Alzheimer’s disease,” Chen says. “Sonobiopsy holds significant promise as a noninvasive technique for molecular diagnosis and early detection of brain diseases and is expected to complement existing neuroimaging methods and extend beyond the field of neurooncology.”
— Josh Hildebrand is the assistant editor of Radiology Today.
References
1. Brain tumor - diagnosis and treatment. MayoClinic website. https://www.mayoclinic.org/diseases-conditions/brain-tumor/diagnosis-treatment/drc-20350088. Updated April 21, 2023.
2. Yong RL, Lonser RR. Safety of closed brain biopsy: population-based studies weigh in. World Neurosurg. 2013;79(1):53-54.
3. Di Bonaventura R, Montano N, Giordano M, et al. Reassessing the role of brain tumor biopsy in the era of advanced surgical, molecular, and imaging techniques-a single-center experience with long-term follow-up. J Pers Med. 2021;11(9):909.
4. Alahmari A. Blood-brain barrier overview: structural and functional correlation. Neural Plast. 2021:6564585.
5. Yuan J, Xu L, Chien C, et al. First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound. NPJ Precision Oncology. 2023;7(1).
