An Updated Prospective Quantitative Analysis of Symptoms and Safety for Human Low-Intensity Focused Ultrasound Neuromodulation
Year: 2026
Type: article
Abstract: OBJECTIVES: Low-intensity focused ultrasound (LIFU) is a noninvasive neuromodulation technique with a favorable safety profile in healthy volunteers. Participant-experienced symptoms, however, remain inconsistently measured, and prospective benchmarks are lacking. Here, we prospectively characterized symptoms associated with LIFU neuromodulation across eight studies using a standardized Report of Symptoms (ROS). MATERIALS AND METHODS: ; mechanical index 0.5-1.4). The ROS rated 17 symptom domains from 0 (absent) to 3 (severe) before and after each session. New-onset incidence, symptom severity, and total symptom burden were compared between LIFU and sham. The same instrument was applied in 35 patients with chronic pain. Symptom profiles after LIFU were indistinguishable from sham across all 17 domains. RESULTS: The total symptom burden averaged approximately one domain per session and did not increase after LIFU (0.94-1.03; p = 0.120). The postintervention burden was predicted by the baseline burden (β = 0.344, p < 0.001) but not by the stimulation condition (p = 0.226). New-onset symptoms did not increase across up to 27 LIFU sessions (odds ratio = 0.99, p = 0.73) and were weakly and nonsignificantly related to acoustic intensity (ρ = 0.37). CONCLUSION: Across a prospective, sham-controlled data set, LIFU added no measurable symptom burden and was well tolerated in healthy adults, with comparable tolerability in patients. These findings establish a benchmark for the safety of human LIFU neuromodulation and a foundation for its therapeutic translation.
Authors: Aditya Kapoor, Thomas Crahan, Wynn Legon
Institutions: Virginia Tech, Carilion Clinic
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,110
OpenAlex ID: W7221073853