Safety of ultrasound in brain imaging and neuromodulation: A review

Ultrasound technology has become a highly promising tool in the field of neuroscience, particularly in brain imaging and neuromodulation. These techniques not only allow for non-invasive visualization of brain structure and functional activity but also enable precise modulation of neural activity, offering new perspectives for the diagnosis and treatment of brain diseases. Animal experiments and clinical studies have confirmed its effectiveness in brain research and therapeutic interventions. However, concerns regarding its safety remain. This review aims to systematically evaluate the safety of ultrasound-based brain imaging and neuromodulation. We examine the mechanisms that may lead to adverse effects, highlight key acoustic parameters that could impact safety, and summarize the acoustic parameters used in existing studies, along with their associated safety reports. The results indicate that, for ultrasound imaging, structural and hemodynamic imaging are generally safe, but prolonged exposure (>10 minutes) should still be avoided. For high-energy or microbubble-enhanced imaging techniques, strict control of the mechanical index, exposure duration, and microbubble dosage is necessary to minimize cavitation-induced damage. Regarding ultrasound modulation, diagnostic safety standards no longer apply—the safety threshold is significantly higher, with irreversible damage only occurring under high-intensity ultrasound (e.g.,ISPPA=280 W/cm 2 in rodent models) or when combined with microbubbles.Finally, we emphasize the need for further systematic safety studies and the development of more precise safety guidelines for different technical principles and application scenarios to ensure the safe use of ultrasound technology in neuroscience.