Figure 1

Targeted blood–brain barrier opening in non-human primates using focused ultrasound and microbubbles. (a) Neuronavigation-guided FUS system. A 0.25-MHz transducer was attached to a robotic arm and positioned above the NHP head. The T₁-weighted MRI acquired during treatment planning was loaded onto the Brainsight neuronavigation system and was used to guide the FUS treatment. An infrared position sensor located the subject and tool trackers in real-time, guiding the placement of the FUS focal volume within the pre-planned area. (b) Contrast-enhanced T₁-weighted MRI showing areas with BBB opening (colored ROI) in the prefrontal cortex of NHP 3 (MI: 0.4), along the axial, coronal, and sagittal planes. Color bar: normalized contrast enhancement. (c) BBB opening volume for MI of 0.4 and 0.8 (n = 3 per condition). (d) T₁-weighted MRI before FUS (top row), 1 h post-FUS (middle row), and day 1 or 3 (bottom row) for NHPs 1 and 2, respectively. Left (L) side was treated with MI of 0.4, while the right (R) side was treated with MI of 0.8. Color bar: normalized contrast enhancement. (e) T₂-weighted MRI before FUS (top row), 1 h post-FUS (middle row), and day 1 or 3 (bottom row) for NHPs 1 and 2, respectively. (f) Susceptibility-weighted MRI before FUS (top row), 2 h post-FUS (middle row), and day 1 or 3 (bottom row) for NHPs 1 and 2, respectively. (g) BBB closing timeline expressed as the percentage of disrupted volume at day 0 remaining permeable at days 1 (NHP 1, empty symbols) and 3 (NHP 2, filled symbols). Gray area corresponds to the false detection rate (5%), indicating pixels whose value randomly fluctuates above the detection threshold. (h) Robotic arm accuracy. Euclidean (top panel) and angular (bottom panel) deviation between planned and achieved focal volume placement. The values were acquired from BrainSight software 2.4 (www.rogue-research.com). Scale bars indicate 1 cm. FUS, focused ultrasound; NHP, non-human primate; BBB, blood–brain barrier; PCD, passive cavitation detector; MI, mechanical index.