Magnetic Resonance Imaging Monitoring of the Safety of Repeated Low-Intensity Focused Ultrasound Exposure at Three Brain Locations.

Transcranial focused ultrasound stimulation (FUS) integrated with magnetic resonance (MR) acoustic radiation force imaging (ARFI) enables real-time localization of the FUS beam, a highly desirable feature for neuromodulation. Because MR-ARFI requires higher acoustic pressure, it is essential to establish the safety of repeated sonication during both ARFI and FUS procedures. Six macaque monkeys underwent repeated neuromodulation studies targeting three brain regions: the thalamic ventroposterior lateral (VPL) nucleus, anterior cingulate cortex (ACC), and periaqueductal gray (PAG). Susceptibility-weighted imaging (SWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences, sensitive to microbleeds, edema, and lesions, were acquired during each session. MRI signals from target regions were quantified and compared with control regions of interest with similar tissue properties. Signal variability within two SDs was considered negative, indicating no detectable damage. Data acquisition intervals ranged from two weeks to >one year. Histologic analysis with Hematoxylin and Eosin and glial fibrillary acidic protein stains was performed on one PAG target. No evidence of tissue damage was detected at any of the three targeted brain regions on SWI or FLAIR imaging. Signal variability for all targets remained within two SDs. Histologic evaluation revealed evenly distributed staining with no signs of tissue damage or neuroinflammation. These findings apply to both neuromodulation pulses delivered within current guidelines and MR-ARFI pulses exceeding current guideline limits. Repeated sonication of cortical, deep brain, and brainstem regions caused no detectable tissue damage, supporting a preliminary safety profile for clinical applications using similar MR-guided FUS protocols.