Fig. 1. Initial BBB openings in NHPs targeting brain regions relevant to PD.

Successful BBB openings were demonstrated in two monkeys (M1/M2) by delivery of an MR contrast agent (Gd) that does not normally extravasate in the brain. Openings were achieved in the targeted regions with relative accuracy. (A) Axial contrast-enhanced T1-weighted MRI image shows BBB disruption in the PMC (indicated by the red circle; M1). (B) Coronal contrast-enhanced MRI shows BBB disruption in the posterior ventrolateral thalamic region (M1). (C) Axial contrast-enhanced MRI shows BBB disruption in the striatum (both the head of the caudate nucleus and the posterior putamen on one side and the anterior putamen on the other; M2). (D) Coronal contrast-enhanced MRI shows BBB disruption in the midbrain (M2). All the enhancements were largely restricted to the targeted regions. Although the same approach was used for each sonication, the size and magnitude of BBB disruption varied depending on the targeted region.