Summary: Researchers at the University of Virginia have developed a noninvasive focused ultrasound technique combined with microbubbles that halts growth of cerebral cavernous malformations (CCMs) in preclinical models. CCMs are abnormal clusters of blood vessels in the brain and spinal cord that can lead to headaches, seizures, neurological deficits, and in severe cases, life‑threatening hemorrhage. This drug‑free, incision‑free approach offers a potential alternative to risky surgery and stereotactic radiosurgery.
In laboratory studies using a clinically relevant mouse model, focused ultrasound with intravenously administered microbubbles arrested growth in 94% of treated lesions and reduced formation of new lesions when repeated treatments were applied. These results suggest a promising new therapy for patients with familial CCMs and other high‑risk cases, with clinical trials being the next step.
Key facts
- Noninvasive, drug‑free: Focused ultrasound combined with microbubbles stabilized CCMs without additional medications.
- High efficacy in preclinical tests: Growth was halted in 94% of treated brain lesions in mice, while untreated lesions grew roughly sevenfold over the same period.
- Potential surgical alternative: The technique could provide a safer, incision‑free treatment for lesions that are hard to reach by conventional surgery or that carry high surgical risk.
New incision‑free approach from UVA Health
The method uses low‑intensity, pulsed focused ultrasound to drive tiny gas‑filled microbubbles through the bloodstream and transiently open the blood‑brain barrier around cavernomas. This localized, image‑guided opening appears to interrupt the cellular processes that drive lesion growth. Importantly, the effect emerged without delivering drugs or genes, an unexpected but reproducible finding that the research team has confirmed through extensive follow‑up experiments.
“This discovery was serendipitous,” said Richard J. Price, PhD, co‑director of UVA Health’s Focused Ultrasound Cancer Immunotherapy Center. “We were evaluating focused ultrasound as a tool for drug and gene delivery to CCMs and noticed that ultrasound plus microbubbles alone stabilized the lesions. After validating the result repeatedly, we see a clear potential for a simple, noninvasive treatment if clinical trials confirm safety and efficacy.”
What are cavernomas?
Cavernomas (cerebral cavernous malformations) are clusters of dilated blood vessels that can arise in the brain, spinal cord, or elsewhere. While many remain asymptomatic, some cavernomas produce headaches, seizures, focal neurological deficits, or intracranial hemorrhage. Current treatment options include surgical removal for accessible lesions at high risk of bleeding and stereotactic radiosurgery for deep or surgically inaccessible lesions. Both options carry risks and potential side effects.
The UVA team’s ultrasound‑microbubble approach may reduce those risks by offering a targeted, noninvasive way to arrest lesion expansion and, in some cases, lower the chance of new lesion formation.
In their experiments, treated lesions in mice showed a marked decrease in the population of mutant endothelial cells that drive CCM growth. In animals receiving repeated treatments at controlled pressures, new CCM formation decreased by 81%, indicating a potential prophylactic benefit for patients predisposed to multiple lesions.
Price noted that mouse models of CCM are generally more aggressive than human disease, with lesions that can grow rapidly. “Despite that aggressive biology, the response to treatment was striking,” he said. “In some experiments, brain tissue exposed to focused ultrasound plus microbubbles was less likely to develop new lesions. If this effect translates to people, it could be transformative for patients with familial CCM syndromes who develop multiple lesions over their lifetime.”
Because the technology to deliver MRI‑guided focused ultrasound is increasingly available in clinical centers, simulated treatment planning suggests the approach is already technically feasible. However, FDA approval would require clinical trials to demonstrate safety and benefit in humans. The research team plans to pursue translational studies to bridge preclinical results and patient trials.
Mechanistic questions and future directions
Although focused ultrasound is known to transiently open the blood‑brain barrier for drug delivery in conditions such as Alzheimer’s disease, the mechanism linking microbubble‑mediated ultrasound exposure to suppression of mutant cell expansion in CCMs remains unclear. The investigators aim to characterize the biological processes involved and to test whether the baseline stabilizing effect can be combined with targeted drug or gene therapies to eradicate lesions entirely.
“Understanding what happens in that ‘black box’ between ultrasound exposure and lesion arrest is a priority,” Price said. “If we can identify complementary therapies, the combination could move from stabilizing lesions to eliminating them.”
Funding and publication
The research was supported by multiple grants from the National Institutes of Health (including R01CA279134, R01EB030409, R01EB030744, R21NS118278, R21NS116431 and R01CA226899), the American Heart Association (grant 830909), and philanthropic support from the Focused Ultrasound Foundation, Be Brave for Life Foundation, and the Alliance to Cure Cavernous Malformation. Price and collaborator Petr Tvrdik, PhD, recently received more than $3 million from the NIH National Cancer Institute to continue CCM research.
The full study, led by Price and colleagues, is described in Nature Biomedical Engineering and documents MRI‑guided pulsed low‑intensity focused ultrasound with microbubbles as an approach that, in mice, arrests CCM growth and reduces new lesion formation. The research team includes Delaney G. Fisher, Tanya Cruz, Matthew R. Hoch, Khadijeh A. Sharifi, Ishaan M. Shah, Catherine M. Gorick, Victoria R. Breza, Anna C. Debski, Joshua D. Samuels, Jason P. Sheehan, David Schlesinger, David Moore, James W. Mandell, John R. Lukens, G. Wilson Miller, Petr Tvrdik and Richard J. Price.
About this neurology and neurotech research news
Author: Josh Barney
Source: University of Virginia
Contact: Josh Barney – University of Virginia
Image: Image credited to Neuroscience News
Abstract
Focused ultrasound‑microbubble treatment arrests the growth and formation of cerebral cavernous malformations
Cerebral cavernous malformations are vascular lesions of the central nervous system that cause significant neurological symptoms. Current primary treatments—surgical resection and stereotactic radiosurgery—pose risks for some patients. In a Krit1 null murine model representative of human disease, pulsed, low‑intensity focused ultrasound with microbubbles (FUS‑MB) applied under MRI guidance opened the blood‑brain barrier in perilesional regions and halted growth of 94% of treated CCMs at one month compared with ~7‑fold growth in untreated lesions. FUS‑MB treatment reduced the proportion of Krit1 null endothelial cells, and repeated treatments with fixed pressures decreased de novo CCM formation by 81%. These findings support FUS‑MB as a minimally invasive strategy that can safely arrest CCM growth and prevent new lesion formation in mice, warranting further investigation in clinical trials to evaluate safety and efficacy in patients.