Elevating the Discussion: Focused Ultrasound Safety Standards 

This blog discusses recent adverse events (AEs) in focused ultrasound brain treatments that have prompted concern within the field about: 1) transparent reporting of focused ultrasound device power and parameter settings and 2) establishing safety standards that are specific to therapeutic ultrasound. 

Investigators and clinicians at two centers performing focused ultrasound treatments for brain disorders recently reported unexpected and significant AEs in three patients. Serious AEs are a rare occurrence with focused ultrasound brain treatments, and the Foundation extends sympathy to the patients and families affected by these unusual events. 

Summary of Reported Events 
On October 31, investigators at the West Virginia University (WVU) Rockefeller Neuroscience Institute wrote a letter to the editor of the journal Brain Stimulation describing an AE due to micro-hemorrhages and edema within and beyond the target area that led to loss of consciousness, intermittent confusion, poor memory recall, and other signs of brain injury. The AE occurred when low-frequency focused ultrasound neuromodulation was being administered in a clinical trial participant undergoing treatment for substance use disorder. 

A few days later in early November, two serious AEs were reported in patients in Madrid, Spain—one with essential tremor and one with Parkinson’s disease. Both patients had developed symptomatic brain hematomas while undergoing focused ultrasound ablation procedures at the Centro Integral de Neurociencias (HM CINAC). These AEs were reported in CNS Neurosurgery. 

Both centers were using Exablate Neuro focused ultrasound devices manufactured by Insightec, but one was a low frequency device (predominately used for blood-brain barrier opening) and the other was high frequency (used for ablative lesioning). The AEs appeared to be associated with the presence of unwanted and unexpected inertial cavitation, which is described by The American Institute of Ultrasound in Medicine (AIUM) as sudden and violent bubble collapse that can potentially damage biological structures. 

Researcher Response 
Two focused ultrasound researchers with technical expertise formally responded about the WVU neuromodulation case. Kim Butts Pauly, PhD, professor of radiology at Stanford University, and Elsa Fouragnan, PhD, professor of neuroscience at the University of Plymouth, each wrote a letter to the editor of Brain Stimulation to share their professional insights on this issue. Importantly, their letters stressed how critical it is to report all power and parameter settings when delivering ultrasound energy to patients, as one publication above originally did not, citing that including some proprietary settings was prohibited by the manufacturer. With transparent reporting, investigators and collaborators could identify which parameter combinations contributed to these AEs and take steps to prevent similar events in the future. 

While maintaining proprietary information is important, because we need successful businesses to make results widely available to patients, it should not take precedence over patient safety. If one treatment site identifies a problematic power setting or monitoring issue, ethical responsibility dictates that this information be shared so that similar AEs are not repeated. 

After working with the clinical trial sponsor, the WVU group published additional information to include all ultrasound parameters, further context on the clinical trial, and “the role of acoustic feedback as a safety mechanism.” The Foundation is supportive of this publication, which provides expanded knowledge of the event and enables the entire field to understand it as treatments continue to evolve.  

Focused Ultrasound–Specific Safety Recommendations and Standards 
Unwanted side effects and AEs in the use of both high- and low-frequency focused ultrasound can be decreased by the advancement and adoption of safety standards that are specific to the field. 

Currently, the regulatory standards related to cavitation apply only to diagnostic ultrasound imaging. In therapeutic ultrasound applications, however, the exposure parameters—especially frequency, along with pulse length, pulse repetition, skull characteristics, tissue properties, and the absence of contrast agents—differ substantially from diagnostic settings and may require consideration of additional factors beyond acoustic pressure alone. 

Several organizations have been working to develop recommendations and safety standards for ultrasound devices, including AIUM, the International Transcranial Ultrasonic Stimulation Safety and Standards (ITRUSST), the National Electrical Manufacturers Association (NEMA), the Institute of Electrical and Electronics Engineers (IEEE), and the International Electrotechnical Commission (IEC). Learn more about some of these efforts below under Recommended Reading. 

Foundation Efforts and Next Steps 
The Foundation encourages investigators to continue pioneering new treatments—as the diseases we are treating also have significant impacts on patients’ lives—while widely sharing the successes and the unavoidable failures. Managing this process well minimizes risks to patients in clinical trials while simultaneously advancing the development of this important technology. 

Because we do not yet have standards for all therapeutic ultrasound applications, reporting all exposure conditions (including power settings) is paramount as the field strives to establish its safety standards. 

The Foundation remains committed to safe and effective clinical adoptions while supporting standardization efforts by incorporating relevant input from the field. 

Beyond brain applications of therapeutic ultrasound, AIUM and the Foundation hosted a series of cavitation monitoring workshops in 2021. Based on that series, an independent working group drafted a technical specification on cavitation detection and monitoring for different applications of focused ultrasound, including blood-brain barrier opening, histotripsy, and drug delivery — all with or without injected cavitation agents. The first draft was presented during the October 2025 IEC meeting and will be advanced as a new work item at IEC’s Spring 2026 meeting. 

The Foundation’s Research Director for Applied Physics, Frédéric Padilla, PhD, and Gail ter Haar, PhD, first published Recommendations for Reporting Therapeutic Ultrasound Treatment Parameters in 2022.